Global Warming Adaptation Funding Responsibility

One of the common refrains at various international climate conferences has been that because the developed world is responsible for a vast majority of the CO2 added to the atmosphere through industrial processes (i.e. neglecting deforestation and agriculture) they are principally responsible for global warming; therefore, due to this responsibility the developed world should be financially obligated to help other “developing” nations transition to a cleaner energy and transportation infrastructure. While it cannot be argued that the developed world is certainly responsible for a majority of the industrial CO2 added to the atmosphere, to make the argument that they should be obligated in any way financially to other parties due to blame for global warming is suspect. There are two important points that must be made for those individuals that are intent at assigning blame for the purposes of acquiring additional financial resources.

First, the idea of developed nations and developing nations as the single delineation point separating the world with regards to responsibility for global warming is inappropriate. Instead one should add a second division point within the developing nation pool that separates advanced developed nations from their slower developing counterparts. These advanced developing nations (ADN) include: China, India, Russia, South Africa, Brazil, Mexico, Saudi Arabia, Iran and Ukraine. ADNs have certainly contributed significant amounts of CO2 to the global warming problem for between 1990 and 2012 they contributed 46.4% of total global industrial CO2 emissions. Therefore, to presume that the global warming issue is entirely the fault of the developed world is irrational. Second, it could be argued that the ADNs should shoulder more of the blame for global warming than the developed nations because they focused on rapid energy infrastructure expansion versus global environmental stability, thus failing to learn from the actions of the developed world.

The ADN countries, especially China and India, did not have to resort to constructing of a massive number of coal and natural gas power plants to grow their economies, especially after the science of global warming was accepted by the mainstream scientific community in the late 1980s. These countries should have foreseen the future problems derived from following the developed nations down the CO2 rabbit hole and instead have constructed their energy infrastructure around nuclear and/or geothermal sources if a rapid buildup was desired. Realistically this poor planning has placed unnecessary and significant pressure on the global community to hasten CO2 mitigation and further increased the work required to do so both economically and politically. Supporting this unfortunate industrial path are CO2 emissions by specific developed and ADNs between 1990 and 2012 as shown in table 1.

Table 1: CO2 Emissions by Specific Countries between 1990 – 2012* (1)
* CO2 emission values in gigatons (billion tons);
Note: Developed World = USA, the 27 countries representing the EU, Japan, Australia and Canada;

While the developed world is responsible for a majority of the existing emissions, the problem is the change in emissions from 1990 to 2012. In 1990 the developed world was responsible for about 59.7% of direct global industrial CO2 emissions whereas in 2012 the developed world was responsible for only 41.2% of these CO2 emissions. Initially one may conclude such a change as understandable because the developing world became more modern and industrialized, thus an increase in industrial CO2 emissions would be expected. While true, the problem is not the change in the slope of the ratio, but the magnitude.

The total global emissions produced by the developed world have increased by only 0.44% between 1990 (11.19 gtons) and 2012 (11.24 gtons) thanks in large part to reductions by the EU, despite countries being added to its roster, whereas the global emissions produced by the ADNs have increased by 112.6% between 1990 (7.56 gtons) and 2012 (16.1 gtons) thanks in large part to increases of 292.8% and 198.5% in China and India respectively. Note that this increase is actually larger than the absolute percentage presented above because in 1990 the collapse of the Soviet Union lead to a large decrease in CO2 emissions that Russia has yet to recover (CO2 emissions were 27% lower in 2012 relative to 1990). If the ADNs learned from the developed world regarding the dangers of building an energy infrastructure on carbon, then their emissions certainly would have increased, but at both a pace and absolute value much lower than has actually happened.

Overall it is difficult to fault the developed nations for the Industrial Revolution. The idea behind the Industrial Revolution was to improve societal quality of life; however, with no “roadmap” to accomplishing such a task it is understandable that mistakes could be made, especially when the science behind and acceptance of global warming were not well regarded and those favoring it were in the very small minority. Therefore, CO2 emissions created by developed nations from the onset of the Industrial Revolution to the early 1980s can be regarded as “ignorant” emissions. The issue of blame becomes problematic for the ADNs because they observed how the developed nations expanded their economies and the quality of life of their citizenry, but also should have seen the eventual cost associated with the methodology of that advancement. It is akin to overcharging things on a credit card; sooner or later the bill will have to be paid.

Understand that the responsibility of those “ignorant” emissions should still be assigned to the developed nations, for the consequence of forging ahead into the unknown is a negative aspect of that unknown. However, the ADNs are at fault for not learning from those consequences. Their “ignorant” emissions are nearly non-existent because they knew the consequences associated with a fossil fuel heavy energy infrastructure forged by the developed world and accepted those consequences by mimicking the construction methodology during their own energy infrastructure advancement.

To this point ADNs cannot argue that there was sufficient uncertainty pertaining to the development and deployment of a large nuclear infrastructure because France, and to a lesser extent Sweden, created that very blueprint in the 70s. In addition Iceland created the blueprint for geothermal, thus the two major cost similar alternatives to coal and natural gas in the 80s had country-centralized examples of their widespread deployment. Note that solar and wind were incredibly unreasonable economically and technically at this time, and there is some legitimate argument that these characteristics still persist despite growing popularity, thus expecting ADNs to embark on a wind and/or solar centralized energy infrastructure would be unreasonable. However, there should have been no uncertainty regarding whether or not nuclear and geothermal were viable and cost effective sources of energy generation.

This behavior by the ADNs disqualifies them from making monetary demands from developed nations at international climate conferences to aid in the transition from a fossil fuel energy infrastructure to a non-fossil fuel energy infrastructure. They had the ability to guide that transition for much less money and refused to take the proper path in lieu of perceived faster economic growth. However, as alluded to above it is important to distinguish between the ADN and other nations like the Maldives, Bangladesh, etc. for they will bear great consequences from global warming and have contributed almost nothing to induce those consequences. Therefore, it is important to ensure that these countries receive sufficient funds from the rest of the global community to effectively adapt to global warming consequences. Overall although there should be little exchange of money between the developed world and ADNs, it is of the utmost importance for these two groups to cooperate in the goal of carbon emission mitigation to neutralize as many negative outcomes from global warming as possible.


Citations –

1. Oliver, JGJ, et Al. “Trends in global CO2 emissions; 2013 Report.” The Hague: PBL Netherlands Environmental Assessment Agency. 2013. Ispra: Joint Research Centre.

Living up to the promise of America by establishing a Guaranteed Basic Income

The birth of the United States was built on the concept of meritocracy where if an individual worked hard he/she could carve out a comfortable existence and if that individual worked smart he/she could become wealthy regardless of position of birth. This feature is one of the major reasons the United States rose from a fledgling nation into the most powerful nation in the world. Unfortunately the inherent nature of this meritocracy has been systematically diminished to the point where at least 46.2 million people (15% of the population) are currently living in poverty (a single individual less than 65 living on less than $12,119 per year or an individual 65 or older living on less than $11,173) in addition to 16.1 million children (21.9% of the demographic).1 However, on their face while these numbers are troubling understand that an individual does not simply move from “difficult life due to lack of financial resources” to “normal life with sufficient financial resources” if that individual earns $12,500 instead of $11,500; therefore, many more people suffer from a version of quasi-poverty that is not encompassed by simple statistics.

Some may attempt to explain this new reality by portraying modern individuals who are impoverished as lazy or not as smart as those in the past, but those holding this belief would be wrong. To even suggest that 15% of the population does not have an effective skill set that can benefit society is amazingly foolish. Instead certain individuals and groups, in order to consolidate money and with it power, have hijacked the structure of society. Sadly manipulating this meritocracy aspect of society has diminished the quality of the United States so far that now it typically only rests on the laurels and momentum of yesterday, remaining a world power solely due to the inability of other nations to take the title.

In the past education was the most reliable way for an individual to rise above his/her birth station and when augmented with hard work become wealthy. While education is still important, the certainty of its value has ebbed significantly because of higher secondary education costs paired with a reduced number of quality jobs that demand such an education due to technology advancement and company outsourcing in effort to increase profits. This reality has been exasperated by numerous high wealth individuals gaming the system and lobbying for legislation that helps them gain even more wealth limiting the amount that those below them can acquire. Poverty in the United States has become the equivalent of a lobster trap, much easier to fall into versus escaping.

Poverty among senior citizens was once rampant, but the creation of Social Security provided an effective strategy to manage it dramatically reducing senior citizen poverty. Unfortunately and somewhat peculiarly while Social Security manages senior citizen poverty, Americans under the age of 65 utilize a patchwork of programs including unemployment insurance, welfare, food stamps, housing allowances, training programs, etc that clearly have not done the job of reducing poverty. This inability to reduce poverty occurs in part because of the high entry costs into the job market for those with low sets of skills or those who have been unemployed for a significant period of time because typically these individuals cannot acquire jobs that have benefits and wages that of significant size in absolute terms or even relative to the benefits currently provided by government. Basically the effective marginal tax rate for taking these jobs is too high. Sadly most of these jobs also have very little room for advancement, thus they become what is commonly regarded as “dead-end jobs”.

Clearly for the United States to revive its superiority something needs to change with regards to how it treats its poor. The major reason why the poor struggle is not a lack of commitment, effort, gumption or intelligence, simply examining the lives of most working poor reveals these obvious conclusions, the chief problem is a lack of opportunity. This lack of opportunity is largely created by a lack of money. A pure no-strings monetary payment to individuals, commonly referred to as a guaranteed basic income (GBI) or simply basic income (BI), can reopen the door of opportunity for the poor allowing them to tap into their creativity and intelligence instead of burying it in a “dead-end job”. It is unclear exactly how many technological, societal and/or economic advances have not been made because a creative individual had to put food on the table versus cultivating a natural talent, but whatever the number it is higher than it should be.

The chief advantage of the BI is how it directly addresses the disadvantages of poverty. One of the problems with discussing poverty is that most of the discussion is conducted by individuals who have never experienced it. A number of people who are impoverished do not start that way, but instead experience a dynamic income shock that cannot be managed effectively due to a lack of savings. Most of these people have jobs, but the wages are so low that they are unable to save effectively because their funds go towards elements critical for survival. Eventually something goes wrong, the individual gets fired, gets sick, has a large single fixed negative monetary event like his car breaking down, etc. creating a financial hole.

While most are able to recover from this initial setback, similar events typically occur again and again deepening the hole ultimately leading the individual into poverty due to existing debt. Basically the individual never has the ability to climb out of the hole because his/her wages are not large enough to overcome these periodic unforeseen payment events, most of which are not the fault of the individual. This is the dynamic nature of poverty where in most situations it is a gradual descent, individuals initially falling then climbing up a little then falling a little more, versus a catastrophic fall. The incorporation of a BI would give these individuals an effective means to climb out of these dynamically formed holes.

One of the more popular advantages of a BI is that it would increase functional mobility allowing people to move to where specific jobs are available without fear and uncertainty. Any person in business would report that an important element for success is eliminating, or at least limiting, uncertainty; a BI would allow an individual the ability to think ahead and create a strategic plan without having to make risky assumptions. It would also allow people to work in jobs that positively influence society, but are not recognized as important by society, especially in terms of salary, like working at nursing homes, teaching special needs children, working as a lab tech trying to cure cancer, etc.

Another advantage of a BI is a possible reduction in criminal recidivism and initial criminal behavior. Most individuals who are not born rich can attest that the current job environment is one of the most difficult in U.S. history; however, for individuals who have some form of criminal record and are not celebrities the market is even more difficult. This difficulty creates a negative feedback loop where a number of individuals have no other recourse for survival than to commit more crimes creating a “revolving door” relationship with prisons. A BI would eliminate this negative feedback loop and if engaging in criminal activity could result in the loss of the BI it would reduce the probability that individuals who lack a criminal history become criminals out of financial necessity.

An indirect environmental and economical advantage of incorporating a BI is a dramatic reduction in homelessness, which will increases property and home values throughout the country. Additionally a consistent income will allow everyone the opportunity to eat and exercise properly as well as have general medical checkups, which will be one element in the puzzle to reducing medical costs among the poor and further reduce emergency room visits and crowding. In fact these outcomes have already been supported by past small scale BI experiments.2 This savings could even transfer over to reduced insurance premiums due to an overall healthier candidate pool.

However, despite all of these side advantages to a BI, including bolstering a social and moral sense of justice that is supposed to be defining characteristics of the U.S., the overall purpose of a national BI is to address the basic needs of an individual without requiring that individual to work. Therefore, it is important to establish an effective range of costs that a BI must encompass to achieve such a goal over simply establishing a BI at some arbitrary number like $6,000, $10,000, $15,000 or $25,000. So what are basic needs and how much would they cost?

Food and water costs are the most essential elements that must be included in the BI. While food is essential, gourmet food is not. Normally food stamp benefits average to approximately $2-$3 an individual a day.3 This amount is currently sufficient for survival, but no rational person can conclude that this amount allows an individual to optimize his/her potential or even remain reasonably healthy. Therefore, increasing this “amount per day” allotment for a BI is imperative.

Some estimate that for individuals at and below the poverty line 1/3 of their income should go towards food. Taking an income at the poverty line this “rule-of-thumb” would develop a food allotment at $10.49 - $11.07 per day. This value is ridiculously high in the context of reasonable health survival, which is the intent of a BI, thus this value cannot be utilized. Suppose the BI assumed food costs at $5 per day. Alone such a quota heavily restricts individuals from eating at restaurants that are not defined as “fast food” and it also slightly compromises the ability to consume significant quantities of daily meat. The biggest problem with this dollar amount is the consistent purchase and consumption of fresh fruits and vegetables. However, despite these restrictions $5 per day should be sufficient for proper health for individuals who have access to supermarkets and shop wisely making sure to take advantage of sales. At $5 a day the food portion of the BI would total $1,825 per year.

Clearly a BI needs to include shelter costs and essential elements within that shelter including heating and cooling. Note that some individuals use cheaper geothermal/solar heaters in their homes, but these are rare nationally leaving the chief method of heating as electric, natural gas, oil or propane furnaces. Among these heating mediums, both oil and propane are overpriced, so individuals with these types of centralized heating systems should instead utilize electrical space heaters for warmth. While natural gas can be price comparably to electricity, natural gas is not as price stable as electricity complicating the estimation and overall budgetary issue for a BI. Therefore, calculations for heating/cooling for a BI will utilize an electric furnace as standard.

For a standard 2,000 sq ft space in a climate encompassing the state of Indiana electric heating and cooling costs can be estimated at $2,332 for a year.4 Clearly there is some standard deviation in this number based on regional climate; an individual living in Western Washington State is going to have lower heating and cooling costs than someone living in North Dakota; also electricity prices vary depending on where one lives; however, the number above is regionally average enough to provide an accurate assessment for a fixed BI. While a 2,000 sq ft living space is nice, the purpose of the BI is to address a minimum healthy standard of living, thus it is not reasonable to expect an individual on the BI to live alone in a residence of 2,000 sq ft; 700 sq ft is a more appropriate space. While it may be questionable to make a direct proportional comparison between size occupancies, it is the strategy that will be used here. Based on this information the BI should assign $816 for yearly heating and cooling costs. Also most communities charge their residence for sewage, water and trash removal with a national average for these services totaling $900 in a given year ($75 a month).

Clearly not all individuals can live in environments where all necessary amenities (jobs and food) are within walking distance or have available public transportation, thus there must be a BI allotment for travel. Assuming that an individual travels 40 miles a day with a vehicle that gets an average of 30 mpg then using the national average gas price of $3.25 per gallon yields a BI travel allotment of approximately $1,580 per year.

One of the biggest questions is how the Affordable Care Act (ACA) subsidy system would change in an environment with individuals receiving a BI. While this interaction is unknown, regardless of any influence there are certain preventative healthcare elements that could be viewed as necessary such as dental visits, basic medical check-ups and the occasional over the counter purchase of some regulated treatment for a random ailment. Based on current costs a medical allotment of $75 a month ($900 a year) should be a reasonable inclusion in any BI package.

The final and most complicated element of a BI is shelter. It is not the responsibility of a BI to allow an individual to reside in any city in any state in the country; however, it is reasonable that an individual should be able to select from numerous living environments and have the possibility to live alone, not be forced to live with roommates due solely to financial necessity. For the moment the more complicated nature of home ownership will be excluded from influencing a BI because owning a home should not be expected as a valid element in calculating what is necessary for survival, thus focus will only be placed on rental properties.

Average U.S. rental costs total approximately $819 per month, but this number has a significant standard deviation between the five most expensive rental states: Hawaii ($1,235), California ($1,118), New Jersey ($1,058), Maryland ($1,044) and Massachusetts ($987) and the five least expensive rental states: West Virginia ($532), South Dakota ($558), Arkansas ($601), Iowa ($607) and Montana ($613).5 Based on this standard deviation difference utilizing just the average may not be appropriate because of a smaller number high value states like Hawaii and California bumping up the average. Basically if $819 used for the BI instead of that average representing conditions where about half the states are below and half are above this housing allotment, the standard deviation value of the expensive states create a situation where 32 states are below the line and 18 are above it creating an allotment that is too high. Therefore, for the purpose of this analysis the BI will allot $750 a month for housing (26 below and 24 above). Also recall that these values represent averages not minimums, an individual could live in certain areas in expensive states like California or Hawaii, thus there is no state exclusion.

The following table summarizes the total cost of providing an appropriate BI package to a given individual:

Table 1 – Minimum Costs Associated with Healthy Living in U.S. Society

Food = $1,825
Heating, Cooling, Sewage, etc = $1,716
Travel = $1,580
Self Reliant Healthcare = $900
Housing = $9,000

Total = $15,021


There is a concern about the BI value calculated above in the context of building the economy. Proponents of the BI frequently cite that one of the important advantages of the BI is that individuals will be able to invest their time in endeavors that he/she are unable to because that time is needed to work in order to acquire money to survive. However, the above number could restrict this new financial freedom. The question is while from a living necessity standpoint Internet access is not a required element, for individuals who want to invest time in endeavors that they may want to later turn into a career will money have to be given for their occupational necessities? If so then at least another additional $500-600 will need to be added to the BI. Despite this concern this analysis will categorize personal at home Internet access as a luxury similar to television largely because most libraries have sufficient Internet access.

With a logically produced number to represent the BI, analysis pertaining to the viability of such a program can commence. In the rational idealist proposal the BI is given to all citizens of the U.S. regardless of age, income or other demographic similar to how Alaska’s Permanent Fund Dividend is given to Alaskan residents. Some would argue that a BI should be extended to all individuals living in the U.S. regardless of citizenry, but this idea politically is almost an immediate non-starter and is morally and practically questionable. Unfortunately this rational idealist position immediately runs into a problem regarding costs.

Taking current population data there are approximately 317.5 million individuals living in the United States. In 2011 it was estimated that there are approximately 11.7 million illegal aliens and an additional 28.7 million legal aliens (individuals who are legal residents, but not citizens or are on some form of visa),6 this value should still be reasonably accurate. After these eliminations the remaining population that would receive a BI is approximately 277.1 million. Taking the BI calculated above the federal government would be responsible for paying out approximately 4.16 trillion dollars to support this BI every year. Unfortunately in 2013 the revenue of the federal government totaled 2.774 trillion dollars and federal expenditures totaled 3.454 trillion dollars in 2013, this additional cost is not viable even with major changes to both revenue and spending streams. Note that this cost only eliminates the simplest BI, one with only a citizenry restriction; it does not eliminate the idea of a BI itself.

So what restrictions would be necessary and fair to create a cost structure that is viable? The first logical place to apply a restriction is on income. The purpose of a BI is to help support those individuals who have low to no incomes because for some reason they were unable to acquire sufficient opportunities to acquire wealth or failed in those opportunities. Assigning an appropriate income ceiling for eligibility is tricky because one must exclude a sufficient amount of individuals who do not need the BI. Based on the premise of the BI it stands to reason that eliminating 15% of the population, representative of the top 15% in total assets, would be an appropriate restriction. Assuming that 98% of this 15% are citizens that would eliminate slightly more than 40.7 million (277.1 million * 0.147) leaving approximately 236.4 million eligible for a BI.

Some critics may argue that this income cutoff is inappropriate because there is an income “cliff” that exists just above the cutoff similar to the welfare “trap” that currently exists. Basically suppose the income cutoff was $150,000 then an individual earning $149,800 would receive the $15,000 BI giving them additional disposal income whereas an individual making $150,050 dollars would not receive the $15,000 BI. While this criticism is valid it misses the point. Recall that the purpose of the BI is two-fold: eliminate poverty and increase economic growth by reducing market inefficiency by increasing the spending ratio of existing capital. If the income cutoff were $50,000 instead of $150,000 then this “cliff” issue would be a significantly greater matter in the efficiency and general nature of the BI. However, despite what some believe individuals making $150,050 a year are not poor or middle-class in any respect, remember the cutoff is at the top 15%, thus an increase of 10% in that pre-tax income for individuals in the bracket will not produce significant increases in spending efficiency in the whole marketplace. Also because the BI is based on individual earnings there is no penalty for a rich spouse further limiting any perceived unfairness.

The second restriction should be based on age. Children are less able to take advantage of the direct and indirect benefits associated with the BI. For example upward mobility for children is limited by their lack of skills and desired occupational goals. Additionally most travel options for children are limited to being chauffeured by parents, riding a bike or other self-powered wheeled device or moving on foot, thus any travel allotment is unnecessary. Overall age eligibility at 18 appears most viable because it is the age that society typically recognizes an individual as an adult. Based on general demographical information from the 2010 census this restriction would elimination another 28% of the population, but one must avoid double counting (counting non-citizens under the age of 18 twice once as non-citizens and again as under 18), thus a 1.1 to 1 birth ratio will be applied between non-citizens and citizens. After taking this step to avoid double counting the age restriction eliminates 76.5 million (instead of 88.9 million), thus leaving 159.9 million eligible for a BI.

A third restriction could be assigned regarding an individual’s criminal standing. There are two sub-restrictions that could comprise this criminal history restriction. First, any individual committing a violent felony would be ineligible for a BI for a number of years equal to the time served in prison for the given felony. Second, any individual committing two misdemeanors would be disqualified from the BI for the next calendar year following a two strikes and you’re out type scenario. Non-violent felonies or violent felonies that result in no jail time could count equal to two misdemeanors. It is unclear how many individuals this restriction would eliminate, but the general idea behind it is not financial conservation, but creating a greater moral and community standing for the BI itself. While the moral ramifications of what one does with a BI are typically not the concern of society, it is the concern of society when individuals would use a BI to directly engage in criminal activity. Note that under this scheme no individual would be penalized for previous transgressions, i.e. their criminal history before implementation of a BI would be irrelevant.

Estimating the number of individuals that would be eliminated by this condition is difficult because there is limited information regarding what could be termed “Jean Valjean” criminal activity, i.e. how many people commit crimes for the sole purpose of survival? What is also unknown is how many individuals will stop committing crimes when $15,000 is at stake? Most individuals would argue successfully that most inmates in U.S. prisons could be classified economically as middle class or lower. While some are clearly violent individuals who deserve to be in jail, others allow their boredom (lack of money for opportunities) to put them in situations and/or environments that result in a higher probability of committing low-grade misdemeanors that eventually land them in prison. Others would argue that a $15,000 BI would disincentivize small time drug dealing in urban environments because such behavior is commonly born from the lack of other legal means to acquire funds, thereby further reducing the prison population.

Unfortunately as stated above these possible behavioral changes and others are difficult to quantify, thus for the purposes of this analysis it will be estimated that of the current approximately 7 million individuals on parole7 that half of them (3.5 million), with an additional 1.5 million of the 2.267 million currently incarcerated,7 will fail to maintain a “clean nose” and thus fail to qualify for the BI. Finally about 5% of these individual are non-citizens who would not receive the BI anyways, thus based on these assumptions another 4.75 million individuals would be eliminated from the BI leaving the total number of individuals receiving the BI slightly more than 155 million costing a grand total of around $2.33 trillion.

2.33 trillion dollars is a lot of money, but is significantly less than the previous citizenry estimate of 4.16 trillion dollars and more importantly is low enough that it could still produce a viable BI methodology. However, this methodology will require changes to the current federal government revenue and spending strategies. For starters the most important point when investigating the incorporation of a BI is producing budgetary changes that will create a net gain, not simply create an equal substitution. Currently the federal government is running a deficit both yearly and overall with the overall actual national debt exceeding 16.7 trillion dollars (obviously a general guidepost number is used here because the debt increases daily). While certain individuals heavily overreact to the urgency in which the national debt needs to be addressed, only a fool would suggest that it be ignored completely largely because of lingering interest payments that will increase with time and make stabilizing a BI incredibly difficult. Therefore, incorporating a BI, especially one that will float in value from year to year, needs budgetary changes that will produce net revenue higher than the current budget.

One of the most common points made in favor of a BI is its simplicity and transparency allowing for the consolidation of government “safety net” programs eliminating their cost and associated bureaucracy. These programs include: unemployment insurance, general welfare, supplemental nutrition assistance program (SNAP a.k.a. food stamps), school meal programs, low-income housing assistance, home energy bill assistance, refundable portions of the Earned Income Tax Credit and Child Tax Credit, supplemental security income, etc. All of these programs together generally cost the federal government between $410 billion and $450 billion per year, thus completely eliminating them after the incorporation of a BI will result in equal savings.8,9

Inherently separate from the BI issue itself, additional funds can be cleared by reducing the budget assigned to the Defense Department. Currently their budget slightly exceeds $900 billion, which is estimated to fall to slightly over $800 billion over the next 5 years due to the conclusion of military operations in Afghanistan,9 but even if that $100 billion reduction is accurate $800 billion is still an inflated amount for what it buys and is necessity. Without cutting funding for veterans and current staff/soldiers, at least $300 billion could be removed from the Defense Department’s budget without any reduction in U.S. safety.

As discussed briefly above it is unclear how a BI and the ACA will interact. It is also unclear how a BI and Medicaid will interact. While there should be no interaction between BI and Medicare, Medicaid is built around helping the poor afford health insurance and may no longer be necessary in a BI environment. Currently the federal government spends approximately $324 billion on Medicaid8 and this value is projected to increase significantly in the future, in part due to the subsidies paid out through the ACA. There will have to be significant study regarding who would qualify for Medicaid in a BI active environment. The chief issue in this debate would be hospitalization because as mentioned above the BI will support preventative action; however, the major costs associated with healthcare in the U.S. with younger individuals are dynamic spontaneous events, which frequently require short-term hospitalization that can run into thousands of dollars in costs. For the purpose of this analysis no funds will be transferred from Medicaid to support the BI.

With the administration of a BI it stands to reason that portions of Social Security (SS) will be terminated for it is unreasonable to expect the government to fund a BI and continue to fund SS as it is currently structured. Note that expenditures in SS are broken down into four major categories: the old age and survivors insurance (OASI), disability insurance (DI), Medicare hospital insurance (HI; a.k.a. Medicare Part A) and Supplementary Medical Insurance (SMI; a.k.a. Medicare Part B & D). The OASI is the component most people associate with SS. With respect to establishing a BI it stands to reason that both the OASI and DI components would be eliminated with HI and SMI components remaining, but there could be some possible restructuring depending on how the BI compliments these Medicare programs. Overall the elimination of the OASI and DI programs will free up between $785 billion to $820 billion that can be utilized for a BI.8,10 Note that for now on references to SS will now only entail the OASI and DI, not the Medicare portions.

There are two important points that must be addressed about ceasing SS under a BI program. First, there is the question regarding whether or not a BI is a sufficient replacement for Social Security? Average SS payouts in 2011 ranged from $11,080 to $12,000 and have not changed much since whereas the BI will be almost exactly $15,000; therefore there should be no trouble for most senior citizens moving from their Social Security benefits to a BI. Note that this is a general average that does not include any special considerations for early retirement at reduced benefits or increased benefits from full payments. Clearly there will be a negative shift in benefits for some individuals, but a switch from SS to BI should not adversely affect a vast majority of SS recipients and not grievously affect any current SS recipients.

Second, recall that SS is funded by a tax, thus that tax will have to remain in place so funds can be diverted to the new BI system. However, up for discussion is whether or not the ceiling for this tax should be lifted. While the payroll tax of 12.4% is split evenly between employers and employees at 6.2% each with payment based on the wage of the employee, only a specific amount of that wage is taxed. In 2013 this ceiling was $113,700 meaning that all wages above this value are not subjected to the payroll tax. Due to the fact that the percentage of earnings has risen faster among the rich versus the middle class and the poor this ceiling exempts at least 14% of existing wages from the payroll tax.11

The origin of the ceiling is unclear. Originally SS was supposed to have a wage exemption for non-manual workers with monthly earnings of $250 or more. Therefore, from the beginning the general idea was to exempt richer individuals that held jobs in finance and management. During negotiations this exemption was replaced by the income ceiling because of valid concerns for the exemption creating unreliable coverage for beneficiaries due to monthly income fluctuations.12

One argument for “protecting” the income of the rich is that SS is really nothing but a government run savings program because history has demonstrated that many individuals are incapable of saving for their own retirement even if they have jobs. If this characterization is used then it makes sense that there should be a ceiling of sorts, which would symbolically designate those individuals who have significant amounts of money in that even if they mismanage it they should still have enough left to save for retirement. Also viewing SS through this lens should justify the ceiling because SS is not a progressive program (income transfer), but a savings account where each person gets out of it generally what they pay into it. Therefore, some would argue that eliminating the ceiling is not appropriate.

Unfortunately those who would argue this point, even if correct which is debatable, fail to acknowledge the changing economic environment with the dramatic expansion of wealth for the super rich, especially in correlation to the dramatically increased U.S. population. This change makes using past intentions inappropriate for such an income disparity in a nation with a population of 127 million is explainable on moralistic grounds whereas that same disparity in a nation with a population of 317+ million is not.

Previous estimates have concluded that at least $219 billion can be recovered from lifting the ceiling.13 Note that this estimate was produced in 2022 using IRS data that calculated approximately 1.77 trillion dollars in earnings that were above the current $90,000 dollar cap.13 The increase in the payroll ceiling ($113,700 in 2013) is tied to inflation and other small factors, but wages for the highest earners have increased the fastest among all earners and outpaced these changes; therefore, the ceiling increase has increased at a slower pace than wages for the highest earners. With this trend it stands to reason that a smaller ratio of earnings is falling under the ceiling. Also with the highest earners least affected by the Great Recession this $219 billion estimate should be regarded as a minimum amount that could be acquired by eliminating the payroll tax ceiling. Finally from a fairness standpoint eliminating the ceiling is much more appropriate than increasing the payroll tax percentage.

Although it will be demonstrated later that a BI will not stimulate any significant disincentive to work, another possible change in the payroll tax that could aid workers is change the weight of the tax burden. For example it may help low wage jobs at large corporations if instead of a 50/50 split of the payroll tax the percentage was modified to approximate 33/67 split between the worker and the company (the worker pays 4.2% and the company pays 8.2% of the existing 12.4% tax). This strategy may also limit the illogically high wages and bonuses paid out to CEOs and upper management at higher value corporations. There are some who would portray this strategy as bad for business under the belief that all taxes are bad for business. However, in a consumer driven economy it stands to reason that most, if not all, negatives produced by this change in tax policy would be offset by the positives of increased spending by consumers due to increased revenue both from the BI and from a smaller payroll tax.

Another change to the tax code involves reverting the long-term capital gains tax back to its progressive mirror in the past where capital gains and income were treated identically. Note that a “capital gain” is defined as an increase in the price of a financial asset between when it is purchased and when it is sold where such assets include stock, real estate, collectibles, precious metals, etc, versus a dividend which is a portion of company profits that are paid to shareholders. There are two types capital gains based on the length of time the investment was held before sale: short-term and long-term. Currently short-term capital gains, investments held for a year or less, are taxed at a rate identical to the holder’s income rate whereas long-term capital gains were once similar before being reduced to 0% for the lower two brackets and 15% for all other brackets as part of the Economic Growth and Tax Relief Reconciliation Act of 2001 (popularly known as the Bush tax cuts). This rate remained constant until 2012-2013 when the rate for the highest bracket was raised to 20%.14 Note that there are certain exemptions on certain types of capital gains like collectables and some types of property that are calculated differently.

Some argue that increasing the capital gains tax is not appropriate because it discourages investment, thus reducing the growth probability of the overall economy. Basically a lower capital gains tax encourages investment and creates jobs leading to greater economic growth. However, this argument is old hat because no statistical significant correlation has been demonstrated between economic growth and capital gains tax rates between 1950 and 2011.15 In fact there is greater evidence of a negative correlation between capital gains tax rate reduction and rates of saving and investment than a positive one.16,17 Basically there appears to be no legitimate empirical evidence supporting an argument to maintain a low capital gains tax relative to associated income tax only soft theory and weak anecdotal evidence that does not hold up under empirical scrutiny. The sole point of keeping the long-term capital gains tax lower than income taxes is to provide a tax shelter for individuals who want to neglect their responsibilities as citizens.

Another problem with maintaining non-income equivalent capital gains tax rates is that a vast majority of rich people are able to use certain tax loophole tricks to portray income as capital gains, thus most of the highest 1% actually pay an effective tax rate that is typically 50% less than the rate they would pay if all of their earnings were income like most middle class and poor individuals. For example in 2007 the richest 400 U.S. taxpayers paid an effective rate of just 16.6 percent, far below the 35% rate (under the Bush tax cuts) that they should have paid if their earnings were income.18 In addition to increasing the long-term capital gains tax government must close the “stepped-up basis” rule governing property bequeathed to heirs, which is another common tax dodge by the rich that costs the government hundreds of millions to billions of dollars. Of course if this loophole is closed then there must be appropriate association with the estate tax to avoid any type of double taxation.

Another common argument against increasing the long-term capital gains tax is to encourage individuals to actually sell their assets, basically to avoid what some call the “lock-in” incentive. This argument is nonsensical because no rational individual will fail to sell an asset once it reaches the appropriate value relative to the psychological conditions of the owner and the environmental conditions of the economy that induce sale. If an individual never sells assets due to fear of getting taxed then said individual would never receive any actual benefit from the asset.

This logic suffers from the same flaw as those who claim that people avoid working hard and making lots of money because of high tax rates. So an individual would rather make a gross of $30,000 a year paying about $4,054 in taxes yielding a net of $25,946 a year than make a gross of $80,000 paying about $15,929 in taxes yielding a net of $64,071 a year? Such rationality is completely foolish and unsupported by basic human psychology, existing empirical evidence and general logic. The idea of “lock-in” is just a boogieman that people use to manipulate the situation to get their way, thus it should not be given any credence. There is also evidence that supports the non-existence of “lock-in” in long-term trading.19

Overall increasing the capital gains tax and closing all of the associated loopholes are important steps for increasing government revenue because as discussed above the more money an individual makes the higher likelihood that a higher percentage of that money comes from capital gains not from a wage. Therefore, a low long-term capital gains tax creates market inefficiencies by further enhancing the funneling of money to the wealthiest individuals while similarly removing money from the consumer marketplace. The CBO estimates that more than 90% of the benefits of reduced tax rates on capital gains and dividends will go to households in the highest income quintile with 70% of that going to households in the top percentile.20 Establishing a higher capital gains tax and using those funds to support a BI dramatically reduces those inefficiencies and should be supported by any legitimate capitalist. Overall changing the long-term capital gains tax to the fair and appropriate values reflecting income similarity would increase federal revenues between $134 and $161 billion per year.20

Another strategy to increase revenue is to simplify the tax code by eliminating all of the different filling methods sans single and head of household. The general reasoning behind other methods like joint and married filling separately have become outdated and merely complicate filling in addition to providing unnecessary benefits, especially in an environment with a BI. In addition the elimination of the standard deduction and personal exemption should also help streamline the tax code and increase revenue that can then be more efficiently transferred to the BI program. Finally as mentioned earlier establishing a BI would limit the usefulness of the Earned Income Tax Credit, thus allowing for its elimination. In the recent past it was estimated that making these changes could increase federal revenues by $304 billion ($60 billion from limiting filing options, $99 billion from eliminating the standard deduction and $145 billion from eliminating the personal exemption).13

While these above eliminations are straightforward and make sense, important study should be reserved to identify if eliminating other tax exemptions like “Interest on public-purpose State and local bonds”, “Step-up basis of capital gains at death”, “Capital gains on home sales” “Accelerated depreciation of machinery and equipment” “Employer contributions for medical insurance premiums and care” and/or “Interest on life insurance savings” would be appropriate. Depending on the conclusions reached the elimination of these tax deductions and others could increase federal revenues between $247.85 billion to $740.810 billion.13

Another means to increase revenue for a BI is apply a financial transaction tax (FTT) to stock purchase and/or sale. A stock-based FTT is easy to implement and adds no significant bureaucracy or cost structure to the existing tax system thereby maximizing the net revenue acquired from such a system. In addition to its general simplicity FTTs are currently administered without issue in 40 countries including 16 G20 nations as well as the U.S. itself. While the FTT was larger when it was initially administered between 1916 and 1966, the U.S. currently still incorporates a 0.0034% tax on stock transactions that funds the Security Exchange Commission.

There are two major types of FTT: those based on a flat rate per stock action and those based on a percentage of stock value. The first type involves incorporating a flat additional fee whenever a stock is sold. This fee is not influenced by the value of the stock at sale. For example if a 50 cent FTT existed and an individual purchased 1,000 shares of stock A at $50.00 and then later sold all of those shares at $57.00 that individual would make a gross of $7,000 and have to pay $500 in FTT fees.

Percentage of stock value is exactly as it sounds. Returning to the above example for a 0.05% FTT (a typically value) the individual would make a gross of $7,000 and have to pay $3.50 in FTT tax. Not surprisingly the higher the value and volume of stock the more tax is collected via the second type of FTT versus the first. Typically the second option is favored by a vast majority of individuals because it has the potential to raise significantly more revenue and primarily focuses on individuals that buy and sell stocks at large volume and value (i.e. focuses more on rich traders rather than middle class traders).

An FTT could be applied to other financial transactions as well like bonds, futures, options and swaps. While there is some hope that an FTT could also reduce high frequency trading, which is thought to have a negative influence on market stability, any reduction would be born from a general reduction in trading period because there is no time variance in the tax. Truly reducing high frequency trading would involve incorporating a FTT that was initially high and reduced in size depending on how long the stock is held; i.e. for stocks sold less than 24 hours after purchase the FTT would be 5% versus for stocks sold at least one week after purchase the FTT would be 0.05%. Overall a 2008 report conducted by the G20 concluded that a global FTT could result in an additional $176.9 to $353.8 billion in annual revenue for the U.S.21 This analysis should still be regarded as valid because the U.S. stock market has recovered the value lost from the Great Recession.

Some proponents of the BI would argue that creating an additional surcharge tax on the rich or increasing the highest bracket of the income tax rate should occur for further funding. While understandable this line of thinking may be inappropriate on the same prescript of fairness and morality that one would argue for the BI. A progressive tax system on both the income and capital gains level is appropriate and fair to ensure maintenance of market efficiency, but gouging the rich at rates that exceed 50% solely because they are rich in some name of “public welfare” is questionable. One could argue that the rich have been gaming the system for so long in their favor that applying a surcharge rate over a fixed period of time, not indefinitely, would be justified in correcting the imbalance created by the subversion of the progressive tax system. However, in this particular analysis no such surcharge will be included.

The overall changes in revenue and spending streams proposed above produce the following result shown in table 2 (note that when appropriate certain values were rounded).

Table 2 – Increases in Federal Revenue due to Changes in Revenue and Spending

Action

Eliminating Existing Welfare Programs = $410 billion to $450 billion
Decreasing Defense Budget = $300 billion
Ending SS Retirement and Disability Payments = $785 billion to $820 billion
Eliminating Payroll Ceiling = $219 billion
Increasing Capital Gains Tax to Mirror Income Tax = $134 billion to $161 billion
Eliminating various filing elements = $304 billion
Elimination of various tax loopholes = $248 billion to $741 billion
Addition of a Financial Transaction Tax = $177 billion to $354 billion

Total Monetary Gain = $2.57 trillion to $3.35 trillion

With the total cost of a restricted BI estimated above at approximately $2.33 trillion, the proposed changes cover this cost at minimum estimation clearing an additional 10%, which meets the secondary objective of a positive increase in the balance sheet versus a near equal substitution. The maximum estimation easily exceeds cost clearing an additional 50%. Note that these estimations attempted to be as conservative as possible relative to the real world, thus it is more likely that more money can be made/saved versus less if these elements were put into practice. Therefore, cost of the currently proposed BI should not be an issue.

Eligibility for the BI can be confirmed through filing an individual tax return. Some have argued that the BI should be electronically deposited into each individual’s bank account, but such a strategy seems naïve due to the threat of cyber crime and the questionable belief that everyone thinks that all individuals in society have a bank account and Internet access, which is obviously not the case. Therefore, a check similar to a tax refund sent by mail seems to be the most fair and all-encompassing strategy. Individuals without bank accounts could then use this check to create one with a stable foothold. Later if security concerns are managed the system could move from paper check to electronic deposit. For individuals without a permanent residence they could petition that the check to be delivered to certain federal buildings like post offices where identification would be confirmed through SSNs and/or valid photo identification. Note that this described proposal is not a negative tax that correlates with tax obligations, but is an additional payment based on the above eligibility restrictions. Negative tax methodologies are typically more difficult to administer because of more “moving” parts.

An additional question is whether to distribute the BI on a monthly basis or in one lump sum. A lump sum payment has the power of scale advantage allowing individuals to act immediately on their ideas. For example suppose an individual wants to become a chef, the purchase of a van for a catering service can be made immediately with a lump sum payment versus waiting four to six months if payments are made monthly. Homeless individuals could immediately search for and acquire places of residence with a lump sum payment (deal with security deposits and first month rent) versus waiting multiple months. Also one check over multiple checks will limit overhead costs before any type of transfer to an electrical system, if one even occurs.

However, the disadvantage of a lump sum payment is that it can result in a greater chance of a negative impulse purchase that could result in a financial setback for the individual. Some individuals, especially those living paycheck to paycheck, may not know how to manage “large” sums of money at one time. Overall one could argue that the important question on this issue is does government have a responsibility to place individuals in low risk decision-making environments? Perhaps it would be in the best interest of all parties for government to provide instruction (maybe via pamphlet) regarding budgeting and proper money management with each check.

Outside of cost, the only significant detraction that can be brought against a BI is that it will create a disincentive for poorer individuals receiving the BI to seek work. Not surprisingly this is the same criticism that is used of current welfare programs that created the “force” people to seek work mindset that largely drove welfare reform in 1996 as well as some strange concerns about the ACA; work disincentive arguments involving the ACA are strange because one cannot feed, cloth and shelter oneself on healthcare subsidies. Unfortunately for opponents of a BI this criticism is unfounded on at least two levels.

In the late 1960s and 70s both the United States and Canada embarked on various small-scale experiments with negative income taxes (a program very similar to the BI proposed here). Hum and Simpson along with Levine and Widerquist have conducted analyses of the conclusions drawn from these experiments and overall very little statistically significant disincentive to work was seen in any of the experiments.22-24 In addition none of the disincentive resulted from individuals simply staying at home and eating bon-bons on the couch while watching television.

Some of the change in work response involved individuals taking more time to look for work; basically instead of taking the first job available due to financial necessity individuals looked for a job that better fit their educational background and general interest. Other changes involved reducing work hours from generally larger than average amounts like 60 hours to 50 hours because the additional money from those hours was no longer worth the opportunity costs, clearly something no rational person would find inappropriate. Even if this behavior was problematic in the past in the current economy workers are fighting for every paid hour they can get, thus the environment eliminates this result as a potential problem.

The demographics that had the greatest influence on the “disincentive” were young individuals who normally expanded their education versus working and secondary earners (mostly females with young children). Note that while female reentered the workforce less quickly one could take it as a sign of the times in that in the late 60s early 70s it was more difficult for females to acquire work, thus frequently requiring numerous attempts to get a job. Also one could argue that these changes actually helped the economy by increasing the quality of available human capital, i.e. better rested and educated work candidates.

An important distinction that must be made in the disincentive to work discussion is with regards to the definition of what exactly is a job? One could argue that a job is a task/role that an individual engages in to produce a positive benefit for society. If that is the case then income derived from the task is not relevant to its validity as a job; or is it that if one does not receive some form of monetary capital from performing an action then it is not a job? If the latter is the case then what is the difference between an individual who works with disadvantaged children helping them gain the skills to better interact with society and gets paid $20,000 versus one who does the exact same thing and gets paid nothing? As stated above almost all individuals want to engage in positive tasks both to enhance the meaning of their existence and to avoid boredom, thus individuals will not simply sit on the couch in a BI program. In fact because the BI only covers need it is unlikely that individuals who do not have another means of income will have the funds to partake in leisure activities even the mundane ones like watching television.

One important limitation of the past studies is that the participants were aware that the BI payments were part of a temporary experiment. Therefore, acknowledgement of this short-term viability may have influenced behavior. One possible negative outcome is that these individuals did not permanently leave work because they knew that the BI payments would end after a set period of time and they did not want to lose their means of financial support after that point. However, while such a mindset is possible for the reasons stated above it probably was not a significant influencing factor in their employment behavior.

Realistically one could expect some disincentive to work from a BI only in the low-income (minimum wage) jobs; for example it is incredibly unlikely that an individual leaves a $50,000 a year job simply because they are now receiving $15,000 a year from the government. Also from a logical perspective general human behavior and ambition reduces the viability of any disincentive to work because of the new growth potential created by the BI. The reason for this rationality is that the BI will supplement the low wage allowing individuals in these positions to save creating what could be regarded as a “dream” fund. After an intermediate time using both the low wage and parts of the BI to build the “dream” fund the individual could leave the low-wage job using those saved funds to drive their change of career.

Ironically this departure is not a bad thing because when the departing individual seeks to advance their career in some form it will create a job opening giving a younger individual, more than likely a teenager who is not eligible for the BI, an opportunity to start his/her “dream” fund. With the advancement of technology and the overzealous attitude of business to outsource certain jobs, the number of qualified job openings is the limiting factor for the general occupational marketplace versus available labor as the limiting factor like it was in the 50-80s; therefore, this behavior would actually drive the economy in a positive fashion versus the current environment.

To expand on the above point, in the past (50s and 60s) the qualified laborer was the limiting factor for most occupations. Basically if an individual had the proper qualifications he could get almost any job that fit those qualifications. However, in the current environment the number of available job openings is the limiting factor, thus numerous people even though they have the proper qualifications to work in field x their probability of doing so is low because of fewer openings in the field. Looking at this concept numerically in the past there would be 500 job openings and 473 people available to fill them. In such an environment disincentive to work could be a problem because the labor pool is the limiting factor. Now there are 400 job openings and 1,187 people available to fill them. In this environment disincentive to work is not a problem because not enough of these candidates will remove themselves from the job market to create a labor pool shortage. Overall there is no logical or empirical backing to oppose a BI on the grounds of it producing societal significant disincentive to work.

Another possible question is what are the moral obligations of society regarding how the BI money is utilized and the outcome of that utilization. Basically some would object to the BI because it would be handing over money to individuals who would use it for various vices like alcohol and inappropriate drugs. However, it would be hypocritical to morally judge the decision-making of these individuals for few people judge the moral choices made by various corporations regarding how they spend money allocated from government tax breaks. Overall it stands to reason that some individuals would spend BI money to feed certain negative habits, but most would not and to invalidate the morality of a program based on the actions of a very small percentage of the affected population would be inappropriate. Or do objectors on these limited moral grounds believe that gun ownership should be heavily restricted on all U.S. citizens because of the poor choices made by a select few?

The other question regarding utilization is how to manage those individuals who squander their BI and are left without capital? Are these individuals left to their own devices or should another strategy be incorporated? It is difficult to argue in favor of secondary assistance when the purpose of the BI is clear and its funding will require the elimination of the existing federal safety nets. Therefore, there are two options: one have individuals accept responsibility for their actions in how they spend their BI and if spent improperly deny any additional governmental assistance or two have states provide some level of temporary support for residents. The chief problem with the second option is that individuals may be unjustifiably risky with their BI if they realize that there is a secondary safety net that can protect them. Therefore, unfortunately those individuals who squander the BI should have no general secondary safety net.

Some would ask what would society do about the lost jobs stemming from the proposed cuts to the military, the welfare system and some other government. Of course jobs would be lost because that is how a consumer based economic system operates, when spending and/or need in a particular field decreases the size and structure of organizations providing goods and services to that particular field decreases. It is completely irrational to continue spending money on elements in an environment that are either unnecessary or redundant. Jobs that exist in such an environment based on this irrational spending can be regarded as purely inefficient government subsidized jobs because the defense contractor or government agency that employs person A in that particular job is creating inefficiency in the transaction by siphoning off a portion of the money for itself which then leaves the economy versus that money going directly to the employee.

Any free-market capitalist should be in favor of eliminating such inefficient transactions. For any argument of sympathy for these individuals losing their jobs, why is it that these individuals, most who have had significant yearly salaries and should have large savings accounts, receive sympathy yet there is no sympathy towards thousands of lower paid, but more essential teachers and/or police officers when they are fired? Yes, it will be problematic for those who lose their jobs, but is it better to provide an anti-poverty subsidy for the country or to subsidize a very small number of individuals? The correct answer is rather obvious.

One of the unforeseen concerns from the experiments in the 60s and 70s was that families receiving the BI seemed to have higher dissolution (separation and divorce) rates. The initial analysis of the results showed that black families had a 57% higher divorce rate and white families had a 53% higher rate.25,26 Interestingly enough this outcome may have been the principle reason that a BI was not incorporated in some manner during the Carter administration as strong previous backers, like Senator Moynihan, ended their support because of these supposed increases in marriage instability.

Interestingly further more stringent analysis of this dissolution data in 1990 identified statistical errors that hurt the credibility of these dissolution conclusions.27 Other studies have reported no increase in dissolution rates in separate studies.2 Overall there is still some question regarding the validity of this increase, thus it should not be viewed as an obstacle for incorporating a BI. One thing to note is that some of the increase may have been a positive thing because the BI would increase the probability for abused spouses to leave the relationship, an action that would commonly result in a divorce, but a divorce that no rational individual should oppose.

A secondary side issue is how will charitable giving change in a BI environment? There appear to be two principle motives behind charitable giving: a compassionate action for helping individuals who need assistance (with some having an ulterior motive of demonstrating their superiority to those individuals through that assistance) and a tax write-off. When a BI is administered it stands to reason that there will be less giving inspired by the first motivation because the need to help individuals who have been dealt a negative hand in life will be significantly reduced. Giving inspired by the second motivation will depend on how the tax code changes to encompass the BI; it makes sense to expect the elimination of most of the charitable deductions, thus significantly reducing tax write-off motivations for charitable giving.

Overall it is important to note that the BI will more than likely shift charitable giving from domestic action to international action for as the less fortunate in the U.S. will have a new BI to help them become more productive members of society, individuals in other countries will not have this benefit and some will still require aid because of their circumstance. Therefore, most domestic-based general need charities will see a loss in donations damaging their infrastructure while international-based general need charities should see an increase in donations. It is unclear what will happen to specific target charities like the “Make a Wish” foundation, which does not support general needs, but specific single events.

One concern opponents might have against a BI is there could be a dramatic “rush to citizenship” by legal residents. Some critics may view this behavior as disingenuous because these individuals did not care to become citizens until the BI was administered. It is difficult to argue against this attitude because such action would characterize an individual as someone who only cares about the money provided by a BI. Such a rush of new eligible individuals in the initial stage of the BI could also create a destabilizing influence because of estimations made on the BI receiving population. Therefore, one option to address this behavior would be to initiate a waiting period of two years before one was eligible to receive the BI for any legal resident becoming a citizen after official passage of any legislation that establishes a BI.

Another advantage to establishing a BI is a slight spin-off of the ability of the individual to establish their own business in that groups of middle-income individuals can start their own businesses together instead of relying on venture capitalists and other investors. While most high value investors do bring useful tools and experience, especially connections, to certain investments they also demand an understandable higher return on their investment, which directs more money away from the standard consumer economy creating market inefficiencies. Middle-class investment groups supported by the BI will keep more of this money in the consumer marketplace, which should accelerate economic growth. These groups would also increase credit flow from lending institutions due to increased confidence in repayment. Finally a federal BI can further support economic growth by allowing states to reduce their welfare programs allowing diversion of those funds to build new or reconstruct existing infrastructure or increase salaries for state employees.

One of the lingering issues is what role children should have in the BI. Earlier one of the restrictions for the proposed BI was an age limit eliminating children from receiving any funds, a condition that is in contrast to most BI proposals which award children some funds. The chief concern with giving funds directly to children is that their parents or primary caregivers will have to manage the money and could misappropriate those funds. Another concern would be individuals having children for the purpose of collecting additional capital from government for those children and in order to maximize those returns these “parents” would neglect those children. However, this is only a minor concern because the number of individuals undertaking this strategy should be small.

Realistically if one wanted to include children one strategy would be to pay each child $2,000 per year until the age of 18 when he/she becomes eligible for the BI. This $2,000 would not be given in direct cash form, but instead be placed in a trust for the child so that upon turning the age of 18 that individual would receive a check equal to the given amount (i.e. for anyone born after the incorporation of such a system within the BI would receive $34,000; upon turning 18 they would receive the full BI). If this strategy were incorporated it would add an additional $153 billion per year to the total cost (76.5 million * $2,000).

Overall there are numerous potential advantages provided by a BI, elimination of hunger and poverty, increased economic mobility/freedom, increased economic efficiency, increased economic growth, increased societal creativity, increased societal physical, mental and emotional well-being, reduce criminal activity, etc,. Against all of these advantages there are only three arguments that can be made against the BI. The first opposition is the overall cost of the program and is far and away the most relevant. While the cost of the BI is substantial it has been demonstrated above that if the government is willing to make intelligent and appropriate changes in its spending and revenue streams the costs can be managed rather easily. Even the proposed increases in revenue do not involve unfair and unreasonable tax increases for the wealthy. In fact one could successfully argue that the increases are fair and should be administered with or without a BI.

The second opposition is the belief that establishing a BI will provide a significant disincentive for individuals to work, so much so that gaps will appear in the workforce due to labor shortages creating economic inefficiency and reducing economic growth. However, as demonstrated above this belief is misinformed based more on the blind hope of individuals who do not want a BI versus valid empirical evidence and logic. Maintaining this opposition is foolish for a BI is not a policy that involves “paying people not to work” despite the lies its opponents wish to continually repeat.

The final opposition is the most unfortunate one, based on the belief of unfairness. Basically there are individuals who believe that individuals who would benefit from a BI do not deserve it because they are poor due to their own choices, thus it is not fair for society to “punish” the successful to help the unsuccessful. The moral problem with this belief is obvious and the logical problem is that it assumes that every individual is born under similar circumstance and success is entirely dependent on the choices and actions of an individual. Of course no rational person would agree with this assumption; people are born into radically different circumstances for example some may have poor parents, some rich parents, some one parent, some soon after birth no parents, so in one vein is society to say that the current generation is to bear the mistakes of their past generations? If so, then how is it fair that the “meritocracy” these individuals envision in the U.S. is defined not by the skills of the current individual, but that of their lineage? The simple reality is that anyone who opposes a BI on the notion that in general poor people deserve to be poor then that individual is a selfish, delusional, irrational fool.

The BI should been supported across political spectrums in that Democrats should support it because it addresses poverty in an effective and decisive manner, Republicans should support it because it significantly limits existing market and government operating inefficiencies making the general system more fair and more in line with objectives of capitalism and Libertarians should support a BI because it shrinks the overall size of government and it greatly enhances individual freedom and opportunity. All parties should support a BI because it reduces the influence of past generations on the present limiting the importance of uneven resource distribution created by predecessors, thus creating a more fair playing field where an individual’s success is more dependent on his/her actions not on the actions made by their parents and other parties of the past.

Finally the administration of a BI should not be taken as the first step to entirely privatized world where government stops providing medical, educational, research funding, etc. services. Once again the point of the BI is two-fold: eliminate poverty and increase economic growth by reducing market inefficiency by increasing the spending ratio of existing capital. No one should take it as an invitation to strip government of any power on the notion of “the private market does it better” because despite what some want to believe the private sector and public/government sector need each other to ensure their optimal function and efficiency.

Overall there is little reason to object to a BI as long as it is operated transparently and is cost effective for a BI benefits everyone in society even if some individuals may not immediately realize it.



Citations –

1. “Information on Poverty and Income Statistics: A Summary of 2012 Current Population Survey Data.” ASPE Human Services Policy Staff. September 12, 2012. http://aspe.hhs.gov/hsp/12/povertyandincomeest/ib.shtml

2. Forget, E. “The town with no poverty: using health administration data to revisit outcomes of a Canadian guaranteed annual income field experiment.” 2011. http://public.econ.duke.edu/~erw/197/forget-cea%20(2).pdf

3. Take the Challenge: Living on a Food Stamp Budget. A Toolkit for Members of Congress. 2007. http://frac.org/wp-content/uploads/2009/09/fsc_toolkit.pdf

4. Annual Heating and Cooling Cost Comparison Worksheet. Calculated by Jasper County Rural Electric Membership Corporation. http://www.jasperremc.com/downloads/energyadvisor/GEOTHERMAL%20&%20ASHP/7%2008%20%20h&c%20fuel%20cost%20comp.pdf

5. U.S. Census Bureau: 2006-2008 American Community Survey.

6. “A nation of immigrants: a portrait of the 40 million, including 11 million unauthorized.” Pew Hispanic Center. January 29, 2013. http://www.pewhispanic.org/files/2013/01/statistical_portrait_final_jan_29.pdf

7. Wikipedia Entry - Incarceration in the United States.

8. FY13 Federal Budget Spending Estimates for Fiscal Years 2012 – 2017. http://www.usgovernmentspending.com/federal_budget_detail_fy13bs12014n_807060500010203040#usgs302

9. Policy Basics: Where do our federal tax dollars go? Center on Budget and Policy Priorities. April 12, 2013. http://www.cbpp.org/cms/?fa=view&id=1258

10. Wikipedia Entry – Social Security (United States).

11. Whitman, K, and Shoffner, D. “Evolution of social security’s taxable maximum.” No. 2011-02 September 2011. www.socialsecurity.gov/policy

12. Mulvey, J. Social Security: Raising or Elimi­nating the Taxable Earnings Base. Report for Congress No. RL32896. 2010. Washington, DC: Congressional Research Service. http://aging.senate.gov/crs/ss9.pdf.

13. Sheahen, A. “It’s time to thing BIG! How to simplify the tax code and provide every American with a basic income guarantee.” USBIG Discussion Paper #144. 2006.

14. Agresti, J. “Tax Facts.” Just Facts, October 15, 2012. Revised 04/05/2013. http://www.justfacts.com/taxes.asp

15. Greelye, B. “Low capital gains taxes may not help the economy.” Business week. October 03, 2012. http://www.businessweek.com/articles/2012-10-03/low-capital-gains-taxes-may-not-help-the-economy

16. Huang, C, and Marr, C. “Raising today’s low capital gains tax rates could promote economic efficiency and fairness, while helping reduce deficits.” Center on Budget and Policy Priorities. 2012.

17. Hungerford, T. “Taxes and the economy: an economic analysis of the top tax rates since 1945 (updated).” Congressional Research Service: Report for Congress. December 12, 2012. R42729

18. Internal Revenue Service, The 400 Individual Income Tax Returns Reporting the Highest Adjusted Gross Incomes Each Year, 1992-2007 (Department of the Treasury, 2007), available at http://www.irs.gov/pub/irs-soi/07intop400.pdf.

19. Burman, L, and Randolph, W. “Measuring Permanent Responses to Capital Gains Tax Changes in Panel Data.” American Economic Review. 1994. September:794-809.

20. “The distribution of major tax expenditures in the individual income tax system.” Congressional Budget Office. May 2013. http://www.cbo.gov/sites/default/files/cbofiles/attachments/43768_DistributionTaxExpenditures.pdf

21. Baker, D, et Al. “The potential revenue from financial transactions taxes.” Political Economy Research Institute and Center for Economic and Policy Research. December 2009. http://www.peri.umass.edu/fileadmin/pdf/working_papers/working_papers_201-250/WP212.pdf

22. Hum, D, and Simpson, W. “Economic response to a guaranteed annual income: experience from Canada and the United States.” Journal of Labor Economics. 1993. 11(1):S263-S296.

23. Robert A. Levine et al., “Looking Back at the Negative Income Tax Experiments from 30 Years on,” in The Ethics and Economics of the Basic Income Guarantee, ed. Michael Anthony Lewis, Steven Pressman and Karl Widerquist (New York: Ashgate, 2004), 95-109.

24. Emery, J, Fleisch, V, and McIntyre, L. “How a guaranteed annual income could put food banks out of business.” The School of Public Policy University of Calgary. 2013. 6(37):1-20.

25. Hannan, M, Tuma, N, and Groenveld, L. “Income and Marital Events: Evidence from an Income-Maintenance Experiment.” American Journal of Sociology. 1977. 82:1186-1211.

26. Hannan, M, Tuma, N and Groenveld, L. “Income and Independence Effects on Marital Dissolution: Results from the Seattle and Denver Income-Maintenance Experiments.” American Journal of Sociology. 1978. 84: 611-33.

27. Cain, G, and Wissoker, D. “A Reanalysis of Marital Stability in the Seattle-Denver Income-Maintenance Experiment.” American Journal of Sociology. 1990. 95:1235-69.

Putting the Breaks on Aging

The idea of finding a means to extend and improve the quality of existing life has captured the human consciousness for as long as humans have had societal stability. Early attempts focused on the short-term like surviving the elements, wildlife or even each other whereas modern times have given rise to tackling biological and biochemical obstacles. The process of aging is evident in almost all living organisms and is characterized by an increased probability of disease acquisition, decline in fertility, loss of physiological integrity, increased physical impairment and obviously increased probability of death.

Aging is not principally viewed as a genetically programmed process, but instead an entropic process; it is also typically categorized into either primary or secondary categories where primary aging is the reduced ability to maintain tissue homeostasis without external assistance and secondary aging involves the symptoms derived from this reduction in homeostasis that have an increased probability of occurrence as an individual ages.1 The term “senescence” is frequently used to refer to primary aging. Primary aging is the focus of most research on life extension because it entails the potential ceiling/maximum lifespan for a given organism. The principle challenge of this research is differentiating between causes of cellular aging and the associated effects of that aging.

Numerous elements have been characterized as keys to aging and critical to developing therapies to reduce or even halt aging: telomere length, reactive oxidative species (ROS), mitochondrial dysfunction, macromolecule accumulation, stem cell depletion, inflammatory cascades, calorie restriction, etc.2,3 Unfortunately it is unlikely that focusing only on one of these elements will result in a treatment that will arrest aging in humans; therefore, an important question is how are these different systems interconnected and how do they contribute to aging in a way that can be addressed through pharmaceutical and/or dietary changes with few detrimental side effects?

One of the most discussed issues in aging is the role of ROS damage. The general idea behind the influence of ROS damage in aging, commonly regarded as the free radical theory of aging (FRTA), is that during the course of metabolism and general function cells accumulate free radical damage from oxidative species like superoxides (O2--), hydrogen peroxide (H2O2-) and hydroxyl radicals (OH-), which lead to accelerated breakdown in cellular communication and mitochondrial dysfunction.4-7 Simply stated FRTA suggests that under normal physiological conditions the majority of the time there is a slight imbalance between prooxidants (elements like free radicals) and antioxidants (elements that can be oxidized without biological detriment) that leads to the accumulation of oxidative damage in various cells and pathway essential molecules that increase the rate of function loss seen in aging.

Free radicals create damage by stripping an electron off another nearby molecule in order to pair its lone electron; however, this process has a high probability of creating a substitute free radical in the molecule that lost the electron. This catalytic-like behavior increases the probability that an important molecule loses an electron changing its characteristics and eliminating its functionality. If enough of these molecules are damaged then the biological pathway they are associated with is also damaged. In addition free radical damage can also lead to cross-linking DNA inducing inaccurate replication producing another avenue for cellular damage.8

Some evidence suggests that the central nervous system is most acutely vulnerable to oxidative stress due to increases in lipfuscin and bcl-2 concentrations, reductions in redox active iron and glutamine synthetase expression and increases in oxidized glutathione to total glutathione ratios.9-13 In addition increased oxidative stress is thought to increase glial fibrillary acidic protein expression as an individual ages along with increased probability for the initiation of the inflammatory response without an initial stimulus trigger.14-16

The origins of FRTA stem from Max Rubner’s work on how oxygen consumption within metabolism correlated with longevity in eutherian mammals.17,18 However, overall interest in the validity of the theory was limited due to the belief that even if oxygen free radicals were produced their existence was transient enough that they could not react with other elements. Later though it was discovered that oxygen free radicals were formed endogenously through standard metabolic processes and their resultant activity induced cellular damage and disrupted various pathways.17,19 Denham Harman modified FRTA later to include a central role for the mitochondria due to their production of the vast majority of ROS in cells, especially because as mentioned above ROS damage can induce mutations to create a positive feedback effect that can fosters even greater concentrations of ROS from the mitochondria.20

Further modifications have been made to include other ROS like aldehydes or peroxides despite not being free radicals because they can damage cells through oxidative reactions.21 In fact some now bifurcate FRTA into “strong” and “weak” versions where the strong version associates oxidative damage to lifespan and the weak version associated oxidative damage to age-related diseases, similar to the categorical split in aging itself.6 Very few individuals dispute the “weak” version of FRTA because numerous studies exist showing a correlation between oxidative damage and age-related disease.17,22

Among various model organisms strong FRTA is supported by work with Podospora anserine (P. anserine), Drosophila melanogaster and various transgenic mice, is questionable in Caenorhabditis elegans (C. elegans) and does not appear important in Saccharomyces cerevisiae (yeast).17,23-27 Other research has demonstrated increased aging and age-related symptoms when superoxides are overproduced in humans.28,29

It has been demonstrated in yeast that blocking mitochondrial free radical production at Complex III, overexpression of methionine oxidation repair enzyme (MsrB) and retaining CuZnSOD or MnSOD versus knocking either one out all increase life span.27-30 However, the biggest problem with accepting strong FRTA in yeast is that research has also demonstrated that growing it under complete anaerobic conditions (which would heavily limit oxygen availability and thus reduce the concentration of available ROS) results in a decreased clonal life span.28 The reasoning behind this apparent contradiction may be due to the role of glycolysis. Most yeast require a significant level of glycolysis for energy to drive growth, especially in anaerobic environments, which produce reactive aldehydes and protein carbonyls.31 These metabolic elements may be the chief cause of lifespan shortening in yeast versus oxygen derived ROS agents, especially because the accumulation of protein carbonyls is a strong indicator of age.17,32

C. elegans are probably the most perplexing organisms when trying to draw support for FRTA. One of the more controversial pieces of support for FRTA in C. elegans is a study by Lithgow demonstrating that superoxide dismutase/catalase mimetics increased life spans, but this result has been difficult to replicate instead sometimes demonstrating toxicity depending on the level of expression.33-35 However, even if the Lithgow work is excluded oxygen tension still modulates life span36 and RNAi screens demonstrate that knocking out most of the proteins in the electron transfer chain increase lifespan by approximately 30%,37,38 and decreased mitochondrial superoxide production also increases lifespan.39

Despite the results of the above studies most opponents of FRTA also find evidence for their opposition in C. elegans studies.40,41 However, there are two important separate issues to consider when studying FRTA in C. elegans. First, there is a significant difference between C. elegans and mammals regarding energy metabolism and oxidative stress mechanisms. Obviously mammals rely largely on aerobic mechanisms to produce energy (most notably through the mitochondrial electron transport chain) for any study of glycolysis reveals the paltry amount of ATP it produces. For C. elegans glycolysis and the glyoxylate cycle are more efficient producing more ATP allowing for multiple day survival in anaerobic conditions.42 More than likely this difference stems from evolution as most C. elegans reside in topsoil, which can have low-oxygen content over certain periods of time. Second, the living environment is important for C. elegans for lifespan is directly associated with ambient temperature, thus living temperature must be controlled across comparative studies. Both of these issue can influence the amount of ROS created over a given time period and create replication problems with the results.17

The chief enzymatic defense utilized by the body against free radicals, especially superoxides, is super oxide dismutase (SOD) augmented by catalase, glutathione peroxidase, peroxiredoxins, glutathione (GSH), thioredoxin, ascorbate, uric acid and alpha-tocopherol.43 There are three major family classifications for SOD characterized by the associated metal cofactor: Cu/Zn (binds copper and zinc), Fe/Mn (iron or manganese) and Ni (nickel). Humans possess three different versions of SOD: SOD1 that contains copper and zinc (family 1), SOD2 that resides in the mitochondria and uses manganese and SOD3 that also contains copper and zinc.

The role of SOD in aging has been somewhat controversial because some studies have demonstrated that increasing SOD activity increases longevity while other studies have demonstrated that increasing SOD activity does not increase longevity. There are two explanations for this apparent contradiction. First, there are numerous types of SOD in both model organisms and humans and these different types interact with ROS in different ways. Also because most ROS cannot freely cross cellular membranes they create three distinct extracellular, cytosolic and mitochondrial pools of free radicals and SOD activity is also typically relegated to these pools.44

Therefore, not only do studies need to factor in the type of SOD they need to focus on the compartmentalization of that particular SOD or the other oxidant/antioxidant being studied as well as the concentrations of other ROS. For example two different studies involving the over-expression of catalase produced contradictory results until it was determined that one study over-expressed catalase in the mitochondria showing lifespan extension in transgenic mice versus the other study that over-expressed catalase in peroxisomes showing no lifespan extension.45,46

Second, there may be an element of avoided detriment due to lifespan restrictions. In some organisms free radical damage may have a greater effect on the maximum lifespan than the average lifespan, but in most experiments the studied organisms die before reaching their maximum lifespan. Therefore, if a model organism never lives long enough to reach the point where the damage significantly increases the probability of death then neutralizing free radicals is irrelevant. It would be similar to developing a cure for Alzheimer’s and then giving it to a population that does not live past the age of 40. Realistically to determine whether or not free radical damage significantly influences aging in humans, studies must be performed on humans or other long-lived primates rather than model organisms like C. elegans and mice.

Another one of the issues with testing the role of free radicals in aging is that there is no standard measure for assessing oxidative damage. For example some measure protein oxidation from ROS by observing carbonyl groups in serum47 while others measure the amount of lipid peroxidation or the number of isoprostanes in plasma and urine.48,49 Clearly the best method would be to directly measure ROS, but many molecules within the ROS “family” are unstable, thus difficult to accurately measure directly. Without a standardized measurement to determine ROS induced damage, experimental replication will have an inherent issue for concern.

Another common evidentiary citation by opponents of FRTA focuses on studies that conclude antioxidant therapies have no significant positive effect in reducing mortality or reducing most detrimental outcomes (symptoms) that are derived from aging and in some cases can even increase rates of mortality.50-53 These studies can lead to the seemingly understandable conclusion that if increasing antioxidant concentrations does not significantly retard aging or the symptoms of aging ROS must not have a significant influence on aging.

One explanation for this outcome that could salvage FRTA is the belief that due to basic biological operations and signaling humans will have a certain level of oxidative stress from metabolism and other triggers and produce a certain amount of antioxidants to manage that stress.54 However, based on these concentrations, generated through expression and signaling, cells may not have sufficient receptors to interact with large concentrations of external antioxidants from either diet or supplements. Therefore, it is not that free radicals fail to significantly impact aging or that antioxidants fail to neutralize those free radicals, but due to certain levels of receptor expression cells are not able to internalize these additional concentrations of antioxidants to retard aging, which is why anti-aging therapies using large concentrations of antioxidants do not appear to be effective. Basically compartmentalization is reducing the effectiveness of the treatment.

Another key element to the utilization of antioxidants in the body may be the involvement of iron and other chelators.43,55 Some believe that transitional metal ions like iron and copper aid in the formation of O2-- and H2O2-. Furthermore these metal ions can also produce OH- through additional reactions with O2-- and H2O2 increasing damage probability.56 The most notable reaction born from this possibility is the Haber-Weiss reaction coupled to Fenton chemistry.56

Some compounds contribute to antioxidant defense by chelating these transition metals and preventing them from catalyzing the production of free radicals in the cell. Metal chelating antioxidants such as transferrin, albumin, and ceruloplasmin avoid radical production by inhibiting the Fenton reaction.56,57

The natural low biological iron concentration is supported by a functional metal redox cycling mechanism where antioxidants can actually become detrimental. For example O2-- or various specific antioxidants (like ascorbate) act as the reducing agent in the Haber-Weiss reaction converting Fe(III) to Fe(II), which can then reenter the Fenton reaction, and convert free O2 to OH-.58 Therefore, increases in O2--, H2O2-, redox active metal ions or certain antioxidants can create a positive feedback environment that can create more OH- leading to further cellular damage. Unfortunately the cellular pools of low-molecular weight iron are not characterized well leaving questions to the prominence of this effect.59

It has also been reported that the iron content of cells increases as the cells age normally, which can enhance the above effect.60 Some excessive iron can be removed from the body by regular blood transfusions like in the case of haemochromatosis.58 Additionally, certain polyphenols inhibit the absorption of iron with flavonoids acting as antioxidant agents through free radical scavenging and metal chelation.61 Therefore, if FRTA is a valid driver of aging one promising treatment strategy could be increasing the concentration of metal chelating elements with smaller increases in antioxidants like vitamin C and E.

One of the most important molecules affecting the aging process appears to be NF-kB (quick reminder NF-kB = nuclear factor kappa beta). In a recent meta-analysis comparing age-related genetic expression profiles of mice, rats and humans the most common signature involved the over-expression of inflammation and immune response genes and those tied to lysosomal system function.62 NF-kB is an essential element in the inflammation and immune response; therefore it stands to reason that even without additional evidence supporting its role in aging, NF-kB would be viewed as an important element in the aging process.

Five different molecules make up the NF-kB transcription factor family: NF-kB1 (p105/p50), NF-kB2 (p100/p52), Rel A (p65), c-Rel, and Rel B.63,64 These different molecules commonly associate with one another to form various heterodimeric and homodimeric elements. The formation of these hetero and homodimeric elements is normally required to induce receptor activation as the NF-kb molecules typically remain inactive in the cytoplasm before compound formation through additional interaction of ankyrin-containing inhibitor-kBs (I-kB).63 The I-kB inhibition complex for NF-kB members is typically made up of three different inhibitor elements (IKKa, IKKb, and IKKg).64 Also note that only the Rel members of the family (Rel A, Rel B and c-Rel) have transactivation domains which can activate transcription.64,65

The most common compound element among the NF-kB family is NF-kB1/REL A or (p50/p65), which is commonly regarded as the “classic pathway” and is activated by tumor necrosis factor alpha (TNFa).65,66 This classic pathway has also been identified in having a role in the promotion and pathogenesis of cancer where activation is largely induced by cytotoxic agents and maintained by oncogenic activation of various tyrosine kinases. An alternative to the classic pathway is induced by binding of other TNF family members and processes p100/RelB to p52/RelB.65,66 The alternative pathway components, which includes IKKa/IKKa homodimers, largely regulate survival of premature B lymphocytes and development of peripheral lymphoid tissues.64,67 Both pathways are complex with various cofactors such as CK2 or Akt influencing whether NF-kB compounds will have a gene inducing or gene suppressing effect including multiple overlaps.64 This complexity makes a straight application of “agent that inhibits element x in the NF-kB pathway” as a therapy difficult because in some pathways it will promote survival and in others it will promote death.

Of the five members of the NF-kB family, fully processed NF-kB1 (p50) seems to be the most important. Not only can it form a heterodimer with p65 which can then activate the classic pathway it appears that its formation of a homodimer (p50/p50) can actually inhibit classic pathway activation.68 While the formation of homodimer (p50/p50) can still bind at the kB binding sites, only those Rel family members have the necessary transactivation domains to begin gene transcription. Therefore, homodimer (p50/p50) binding instead of heterodimer (p65/p50) prevents gene transcription and the activation of the classic pathway.68,69

The influence of NF-kB on aging has been studied most often in skin cells where it is cell autonomous because visible signs of aging in various skin cell cultures can be neutralized or even reversed after exposure to NF-kB inhibitors like 4-OHT.70 NF-kB binding activity increases with age in mice in various tissues including the skin, heart, kidney, liver, spleen and possibly even stem cells.70-72 This increased binding is thought to regulate senescence, but only replicative and oncogene induced senescence have been observed.73,74 In addition SIRT1 and FOXO, which are widely regarded as strong longevity signals, seem to inhibit NF-kB.75 Interestingly because of the increased binding, the effect of NF-kB on aging acts as an age-dependent positive feedback effect.70

Although aging is not perceived as genetic the closest thing to an “aging trigger” at the moment could be NF-kB. It has been hypothesized that aging is not actually the natural state of cells instead the aging phenotype is achieved through the continuous presence of sufficient concentrations of NF-kB and expansion of its influence through its positive feedback effect.70 The elimination of NF-kB through inhibitors removed markers of cell senescence like cell-cycle inhibitor protein p16 and enhanced proliferation of progenitor cells in skin. Overall, at least relative to skin, NF-kB activity appears to be continuously required to facilitate aging.

One of the most telling issues regarding NF-kB and general aging is that p52 and p65 expression increases significantly in older organisms versus young ones, yet p50 expression along with IkB inhibitors IKKa and IKKb remain at similar levels regardless of age.76,77 Also while p52 and p65 expression increase, their mRNA expression levels demonstrate no significant increases.77 The most probable explanation for this result is that NF-kB protein retention in the nuclei increases with age. This additional NF-kB also increases DNA-binding activity, especially in major lymphoid tissue including constitutive activation of NF-kB within T and B-lymphocytes and macrophages.78

There also appears to be a relationship between ROS and NF-kB in that ROS can induce NF-kB signaling after their production by pro-inflammatory cytokines like IL-1beta and TNFa and lipopolysaccharide stimulation.79 However, not surprisingly this interaction is complicated by timing where early ROS production can act as important messengers for NF-kB activation ROS produced after TNFR1 engagement only facilitates cross-talk between NF-kB and JNK with respects to inducing pro or anti-apoptotic pathway activation.80 Of course because JNK acts as a pro-apoptotic trigger, depending on the situation it can be a pro-aging or an anti-aging trigger meaning the relationship of ROS and NF-kB is even more complicated. This complication could be why there is some evidence that demonstrates dietary therapies with antioxidants down-regulating the age-related increase DNA-binding activity of NF-kB in addition to neutralizing the increased IL-6 and IL-12 expression.78

As alluded to above NF-kB also plays a role with various important aging-related genetic elements including SIRT (mammalian homolog family for silent information regulator (SIR)) and FOXO.81 SIRT1 physically interacts with p65/RelA protein complex to deacetylate lysine-310 on p65 inducing an inhibitor effect on NF-kB transcription.81 It appears that SIRT6 can also inhibit NF-kB activity by modifying the chromatin structure of promoters that interact with various NF-kB genes, which appears to reduce speed of aging.82,83 This SIRT interaction with NF-kB is one of the explanations to why calorie restricted diets could reduce aging and the expression of pro-inflammatory elements or reducing calories appear to increase expression of SIRT1 and NAD+, which is required to activate SIRT1.84,85

Forkhead transcription factors (FOXO) are the mammalian homolog to the famous DAF-16 protein in C. elegans. FOXO3a seems to induce inhibition of NF-kB by limiting the length of activation for unnecessary inflammation, which reduces cellular damage thereby decelerating aging.86 Whether or not this inhibitory effect is driven by direct inhibition of the NF-kB complex or indirect inhibition of elements that activate the NF-kB complex like TNFa or even both is not completely clear.86,87

One of the unclear issues regarding NF-kB inhibition is whether or not it actually affects the overall lifespan of a cell. Intuitively it would stand to reason that if inhibiting NF-kB causes cells to revert to a younger biochemistry and behavior then their lifespan would increase as well; however, this may not be the case. There could be other age-related signals that correspond to senescence that NF-kB has no effect on, thus NF-kB inhibition may not change cell lifespan, but simply create younger cell activity over the course of that lifespan. It would be akin to individual A living 80 years and aging normally versus individual B living 80 years, but remaining as a 30 year-old biologically for the last 50 years, but still dying at a chronological age of 80.

Another question is how would inhibiting NF-kB affect the immune system because NF-kB has an important role in influencing immune response, especially c-Rel and its initiation of IL-12 production. Among other things kappa light chains are critical components to immunoglobulins.70 One interesting experiment would be to vaccinate a mouse then apply a NF-kB inhibitor and then determine whether or not the vaccination is still effective against the target infection.

In the last five years rapamycin and the mTOR pathway [mechanistic (formally mammalian) target of rapamycin] has become a promising candidate for life extension and recapturing youth. Rapamycin is an anti-fungal agent utilized by various soil bacteria that was used as a possible tumor suppressor and immunosuppressor. The TOR pathway (note that in invertebrates it is normally referred to as TOR not mTOR) plays a large role in nutrient sensing and growth through lipid biosynthesis and storage and is highly conserved among various different species. TOR is activated by glucose, insulin, free radicals and growth factors.88 TOR first gained significant recognition as a potential factor in aging when it was reported that inhibition of TOR complex 1 (TORC1) in invertebrates increased lifespans in yeast, C. elegans and Drasophila.88 Overall mTOR interacts with numerous proteins to form mTOR complex 1 and 2, which have different upstream and downstream activation pathways. Note that rapamycin only legitimately inhibits mTORC1 and not mTORC2, although it can disrupt the structure of mTORC2 after long-term high concentration treatments.88

The two major pathways that TORC1 interacts with that influence aging are first global up-regulation of mRNA translation, including ribosome synthesis by direct phosphorylation of S6 kinase and eukaryotic initiation factor 4E binding proteins.89 Second the down-regulation of autophagy, although this regulation is complicated by compartmental segregation between elements of the TOR pathway and autophagy initiating factors like ULK-1.89-91 Also there is some belief that TORC1 interacts with other dietary/nutrition pathways like insulin signaling pathway, hypoxic response transcription factor Gcn4 in yeast and Sirtuins (SIRT family).92,93 Note that autophagy involves the degradation of proteins and organelles via the lysosomal pathway and has been shown to decline during aging, which may lead to the increase of misfolded proteins and ROS in older cells. These effects have also been tied to the anti-aging results seen from calorie restriction.94,95

Due to an initial belief that rapamycin might have a therapeutic effect against some forms of cancer the National Institute on Aging Interventions Testing Program (NIAITP) conducted studies in cancer susceptible genetically modified mice. The result of these studies identified that the addition of rapamycin treatment in 600-day (approximately 20 months) old mice significantly increased the lifespan of both male and female mice, noting that the increase in females was significantly larger than the increase in males.96 Another unassociated study also produced similar findings of 16% and 13% maximum lifespan extensions in 9-month old male and female mice respectively.97

Another important initial study with rapamycin observed its influence on S6K1 (mice equivalent of S6) knockout mice and concluded that these knockout mice had significantly increased lifespans.98 This study indirectly increased the viability of mTOR as a pathway for aging because it demonstrated a longevity increase in a second genetically distinct mouse class versus the NIAITP study. The supposed pathway of operation was not identified, but the activation of adenosine monophosphate (AMP) activated protein kinase (AMPK) was thought to be an important element. While the importance of its activation is still unclear some believe that AMPK negatively regulates TORC1 through phosphorylation of Tsc2, a TORC1 inhibitor.99

However, it must be noted that the increase in lifespan was only commonly significant in female mice not males similar to the NIAITP study and in contrast to the Miller study.98 Also the knockout mice were significantly smaller in body mass than the non-knockouts, which is understandable due to the growth elements controlled by S6K1. Finally the activation of AMPK may not be a requirement for life extension as rapamycin application to wild type flies resulted in life extension without AMPK activation,100 thus raising questions about the role of AMPK.

One possibility is that the activation of AMPK may simply be a secondary effect of rapamycin with the primary lifespan expanding effect being its interaction with stem cells in aged animals as it enhanced the in vivo replicatory capacity of hematopoietic stem cells in aged animals.101,102 In addition there is some question to whether or not rapamycin is immuno-active or immunosuppressive. If it has a positive effect on the immune system then this interaction may be how rapamycin affects longevity. For example TORC1 inhibition prevents the secretion of “pro-aging” cytokines IL-6 and IL-8 by Ras-transduced cells.94 Another possibility could be that the enhanced autophagy allows the body to eliminate damaged cells before they can secrete negative feedback molecules that would create a damage cascade negatively affecting other healthy cells in the local area including inducing aggregating proteins that could result in misfolded proteins.

Overall it appears that TOR dependent changes with regards to aging at a cellular or tissue level are hypertrophic in contrast to the atrophic degeneration that is thought to occur through ROS driven damage. These changes also support the idea that rapamycin is able to increase lifespan beyond its apparent tumor suppression effect because aging is the result of multiple pathways activating under certain boundary conditions and cannot be significantly prevented by only stopping a single disease or pathology. It must be noted though that rapamycin influence on stem cells is not entirely positive as it can impair pluripotency through a reduction of proliferation and promotion of differentiation of human, and to a lesser extent mouse, embryonic stem cells.103,104

As mentioned above while rapamycin has demonstrated an empirically valid potential as an anti-aging element due to its interaction with mTOR, the biggest concern surrounding its application is its influence on the immune system. Originally rapamycin was viewed as an immunosuppressive element and used thusly,105,106 at times in attempted treatment of cancer, generating the conclusion that giving it to aged individuals, especially in the era of antibiotic resistant pathogens, would be inappropriate because it would increase the probability of infection and the probability of death from infection. However, rapamycin supporters have attempted to counter this claim stating that rapamycin may bolster immune system activity.101,107,108 So which side is correct on this important issue?

Unfortunately the role of mTOR and rapamycin in immune system functionality is quite complicated and time dependent. mTOR is a part of the phosphoinositide 3-hydroxy kinase (PI3K) related kinase family and the PI3K-Akt-mTORC1 complex can be co-stimulated, which leads to activation by molecules like the Cluster of Differentiation 28 (CD28) in addition to various interleukins (IL-x).109-111 One of the initial results from mTOR activation is an increased activation time for CD8+ cells and developmental enhancement of T-helper 17 (Th17) cells.112-114 Therefore, one would expect that inhibiting mTOR via an agent like rapamycin will reduce these effects.

Recall that there are two distinct types of immune responses: innate and adaptive. The innate immune system is the older of the two, much less specific in its assault and activates upon the entry of almost any foreign pathogen. Elements of the innate system include epithelial and mucosal membrane obstructions that aid phagocytosis and lysis, various phagocytes, natural killer cells along with other leukocytes, dendritic cells to begin recruitment of more specialized cells and the eventual release of cytokines, and the beginning of the inflammation response.108,115 If it is determined, through signaling, that the innate response will not be sufficient to neutralize the pathogenic threat dendritic cells can act as antigen presenting cells (APC) to activate naïve T cells to initiate an adaptive immune response.

The role of these dendritic cells in relation to the adaptive immune response is critical to the influence of mTOR on the immune system as a whole. mTOR appears to measure the standing of the immune environment and influences antigen recognition similar to its nutrient-sensing ability.110,111 This influence affects how the dendritic cells act as APC, thus determining their interaction with naïve T cells.116,117 However, this influence is affected by the types of dendritic cells activated and the length of time that mTOR is activated (i.e. the amount of rapamycin utilized).118,119 Short-term treatment of rapamycin increases the concentration of cytokines IL-12 and IL-1beta and reduces Toll-like receptor induction of IFN alpha and beta, which act as one of the first defenses against viral infections.118

Long-term treatment decreases the innate immunity of monocyte-derived dendritic cells both via the conventional method and the plasmacyoidal method utilizing cytokine Flt3 as well as reducing the up-regulation of dendritic co-stimulatory molecules, thus suppressing mature dendritic function.120-125 Also knocking out the raptor component of mTORC1, which generally mimics inhibition, leads to a change in the ability to initiate anti-inflammation through the production of additional phenotypes of splenic CD8+ and intestinal CD11+ cells.126 Finally long-term rapamycin treatment reduced allogeneic T-cell response while increasing regulatory T-antigen specific Foxp3+ response.127

The adaptive immune response is highly specific and is dependent on the type of pathogen present and its characteristics. The principle agents involved in the adaptive response are B cells, which govern the humoral (antibodies) response and T lymphocytes, which govern the cell (white blood) response. The adaptive response is so named because it changes, normally increasing effectiveness, each time a pathogen triggers it. The best example of the adaptive response is the specific antibiotic response to a specific pathogen, primed through vaccination.

In vitro it has been demonstrated that rapamycin reduces B lymphocyte proliferation and plasma cell differentiation, which would also reduce antibody production reducing adaptive immune response efficiency.128-130 Also a hypomorphic mouse model with a disrupted mTOR transcript demonstrated reduced B-cell development, reduced cell proliferation and reduce B-cell and T-cell antibody formation.131 mTOR also appears to be required for B-cell differentiation to plasma cells as well as LPS-induced B-cell proliferation and differentiation.131,132 However, interestingly enough only one part of the mTOR pathway, mTORC2, may be principally responsible for B-cell development due to the activation of AKT through phosphorylation and progressive inhibition of FOXO1.133 Therefore, it could be that mTORC1 governs dendritic cell maturation and development and mTORC2 governs B-cell maturation and development, thus short-term rapamycin treatment only disrupts dendritic cells, but long-term treatment could disrupt both dendritic and B-cells.

With regards to T-cells mTOR plays a critical role in the differentiation of certain T-helper cells, most notably 1 and 17.134,135 Also mTORC2 activates PKC theta which helps promote T-helper 2 differentiation, although it does not appear necessary.136 Also mTORC1 regulates hypoxia inducible factor 1 (HIF1) and is required for glycolysis, related enzyme activity and glucose homeostasis in activated CD8+ cytolytic cells.137,138

While some evidence exists that rapamycin treatment can induce immunostimulation of CD8+ T-cells,139-141 the effect may be derived from enhanced cytokine production by macrophages and may not be induced directly by mTOR inhibition.142 Also in most studies rapamycin treatments have been low dose and short-term, thus there is no evidence that any “enhancement” effect will persist over the long-term.140-141 Additionally most rapamycin experiments are conducted in environments that do not tend to have pathogens, thus eliminating real-world examination of how the immune system may be augmented or compromised. Finally there is some evidence that increased used of rapamycin fosters various inflammatory events like lymphocytic alveolitis, glomerulonephritis and interstitial pneumonitis.143-145 Surprisingly the best feature associated rapamycin may be its CD8+ anti-tumor training ability versus its potential anti-aging effects or other immunosuppressive effects.146-148 However, that anti-tumor effect may come from the reduction in IL-10 concentration born from mTOR inhibition for the IL-10 cytokine is thought to have an immuno-masking effect.

Currently existing results support the position that short-term rapamycin treatment has an overall negative effect on the innate immune system with some positive attributes and more than likely a negative effect on the adaptive immune system; long-term rapamycin treatment has negative effects on both the innate and adaptive immune system. Most rapamycin proponents seem to focus on the niche enhancement of the innate system from short-term treatments; however, clearly short-term treatments will do very little to ward off the negative outcomes of aging, thus as it stands the use of rapamycin as an anti-aging tool comes with an immunosuppressive trade-off.

One of the more interesting factors of the mTOR pathway is its dependency on other signaling factors, which appear to make it a general feedback catalyst. For example mTOR increases the secretion of aging elements from damaged and/or senescent cells, but also increases the secretion of anti-aging elements from younger undamaged/unstressed cells. This feature is most notable in muscle tissue where mTOR promotes secretion of trophic factors like IGF-1 from young cells and cytokines like IL-6 from old cells.149 Also rapamycin may have a negative effect on wound healing as it interferes with the ability of p38alpha to activate mTOR to balance the synthesis of IL-12 and IL-10 to properly regulate CD4+ Th1 response to wounds and tissue damage.150 Specifically inhibition of mTOR promotes IL-12 production and reduces IL-10 more than likely through its cross interaction with PI3K, which is a IL-10 enhancing signal.145

mTOR is not the only major element that can both influence aging and the immune system. As mentioned above NF-kB also plays a significant role in activating immune system elements to initiate an appropriate response.151,152 The major signaling pathway that is utilized to connect NF-kB to the immune system is the toll-like receptors (TLRs) along with IKKb kinase and various cytokines, which influences inflammatory signaling.151-153 As most know inflammation can be a useful element in combating infection and other anomalies, but chronic inflammation can increase the damage probability for various cells through increasing oxidative stress and lipid peroxidation, increasing unnecessary cytokines and inducing matrix degradation through the production of metalloproteases.154,155 Cytokinese play an important role in creating a balanced and appropriate immune and inflammatory response. IL-10 and IL-12 have been previously discussed due to their association with mTOR; however, other cytokines appear to influence aging outside of the mTOR pathway including IL-2, IL-4 and most importantly IL-6 all of which are influenced by NF-kB. The most important of the three is IL-6, which is a pro-inflammatory cytokine that has enhanced expression as an organism ages and is thought to contribute to numerous pathophysiologic conditions.156,157

One of the major reasons suspected for the success of rapamycin in reducing aging and its effects is increased autophagy potential positively affecting cellular senescence. NF-kB influences cellular senescence through changes in apoptotic resistance and autophagy augmentation. The chief role of NF-kB signaling relative to apoptosis is to increase the expression of apoptosis inhibitors like Bcl-xL, and the IAPs along with repressing expression of apoptosis activators like JNK and elements in the Fas pathway.158,159 NF-kB elements IKKa and IKKb activate the mTOR complex to inhibit autophagy.160 So NF-kB and rapamycin actually compete in their influence of mTOR and its associated elements like cellular autophagy. With respects to NF-kB mTOR interaction appears to have negative feedback structure where continued activation decreases NF-kB concentrations and increases STAT3 concentrations to reduce the rate of inflammation and increase autophagy at least in younger individuals.

With the principal causes of aging born from environmental and genetic factors there is great interest in producing various biomarkers to detect and track aging in response to treatments. Officially biomarkers are defined by the National Institute of Health as “features objectively measured and evaluated as an indicator of normal biologic, pathogenic or pharmacologic responses to a therapeutic intervention.”161 The chief problem with developing biomarkers for aging is that the deterioration associated with aging occurs over multiple systems with unknown levels of interdependency. This problem is magnified when considering biomarkers that can be compared across different species. Despite these problems researchers have attempted to define biomarkers among elements associated with oxidative stress, inflammatory markers, telomere shortening and hormones, but these markers have not been supported by longitudinal studies.161,162

In addition none of these biomarkers can be viewed as genuine biomarkers to describe aging, but instead are related to disease where age is the biggest risk factor for their appearance. Also interesting is that these biomarkers tend to be expressed in primary elderly populations (65-80 years old), but not secondary elderly populations (80+ years old).163.164 Basically when individuals exceed 80 years old standard age-related “biomarkers” like blood pressure and various metabolic syndromes do not associated significantly with mortality, which of course is unexpected.163-165 The only “biomarker” that seems to retain its predictability at some level is telomere length.166

This important aging element was discovered in the 1930s when both Barbara McClintock and Hermann Muller identified specialized repeating structures at the end of chromosomes.167,168 These structures were later labeled telomeres and were implicated as critically important for cell division preventing chromosome fusion and an incomplete chromosomal copy. Telomeres are important because of how DNA polymerase operates during DNA replication due to the opposing leading and lagging strands of replication. The lagging strand requires a RNA primer to attach a short distance ahead of the initiation site. However, the genetic material behind that new starting point is not replicated; this is fine if the fragment consists of the telomere, but can damage the cell if there critical information is left behind.

A possible role for telomeres in aging was not identified until the 1960s when Leonard Hayflict famously observed that human cells could only undergo a limited number of cell divisions before death, a behavior now referred to as replicative senescence.169,170 Soon after the identification of replicative senescence Alexei Olovnikov proposed that telomeres acted as a buffer of sorts that “sacrificed” itself during replication so the whole chromosome could remain intact.171 This process was also viewed as irreversible because of the one-directional nature of DNA replication. In the late 70s Elizabeth Blackburn and Joseph Gall formally identified telomeres confirming both McClintock/Muller’s and Olovnikov’s theories.

It was eventually determined that somatic cells were unable to maintain telomere length after a specific number of cell divisions leading to cell death. While somatic cells are unable to maintain telomere length, stem cells are able to replicate at various levels of frequency due to the expression of telomerase, an enzyme derived from the telomerase reverse transcriptase (hTERT) gene172,173 that is responsible for “rebuilding” telomeres so the telomere is never completely lost eliminating any inherent ceiling to cellular lifespan through replicative senescence.

Telomerase expression is high during embryonic development, but is down-regulated almost entirely soon after birth in almost all differentiated adult tissues with the exception of specialized stem cell compartments and down-regulated significantly, but not entirely in cell types that have rapid division frequencies like lymphocytes or skin keratinocytes.174

It is somewhat difficult to draw conclusions from telomere research in vivo because of the differences in fidelity of DNA repair and replication pathways between humans and various model organisms. In most model organisms like mice, yeast and C. elegans the elimination of telomerase is irrelevant for several generations of cellular replication whereas in humans after cutting telomerase concentration in half numerous negative symptoms arise like aplastic anemia, immune system deficiencies and pulmonary fibrosis after a few generations.175-177 Also genetic linkage analysis is rather muddled due to difficult to identify relationships between clinical phenotypes and telomere-related genes.

The belief that telomeres are important in aging is supported by short telomere association with numerous premature aging syndromes such as Werner syndrome, Ataxia telangiectasia, Bloom syndrome, Nijmegen breakage syndrome, Fanconi anemia, bone marrow failure, dyskeratosis congenita, aplastic anemia, pulmonary fibrosis, etc, due to cross-sectional and longitudinal cohort studies.178-181 There was some question regarding the role of telomeres and aging in that some research supports an inverse relationship between telomere length and lifespan,182 but this relationship did not seem to exclude tumor/cancer related deaths and most of the differentiation between telomere length and lifespan occurs between life forms with > 1 kg mass and < 1 kg mass. Also clearly aging is a more complicated process than simply looking at telomeres especially when considering average lifespan, not maximum lifespan the element that telomere influence, in normal functioning creatures is studied more in laboratory tests.

Also in vitro studies have tied telomere length to oxidative stress and damage, which has some compelling anecdotal evidence in that the estimated telomere loss per cell division is 50-100 base pairs, but lagging end-replication only seems to account for a loss of 20 base pairs.183 Therefore, it is reasonable to suggest that the additional loss is derived from oxidative damage.183 If this association between telomere length and oxidative stress is accurate then one may be able to better manage telomere length through anti-oxidative stress strategies. However, as mentioned above these strategies must be more specific and rational than consuming a large quantity of Vitamin C and E.

Previously some argued that the role telomeres play in aging could be neutralized by simply activating telomerase in somatic cells. However, this strategy is complicated because the deactivation of telomerase in somatic cells acts as a form of tumor suppression limiting clonal proliferation and dominance. This reality is demonstrated in actual cancer cells where one general aspect of their enhanced ability to replicate is dictated by the reactivation of dedicated telomerase gene expression. Also there is some question to whether the activation of telomerase can create a dysfunctional telomere, which can lead to a malfunction in the DNA damage response for a cell creating a pseudo-tumor cell.175

Telomerase deactivation is not necessarily a bad thing as restrictions in the proliferation of somatic cells pose a barrier for the growth of aspiring tumor cells. Unfortunately, the telomere mechanism that limits the growth of pre-malignant cells also provides strong selection for cells that no longer respond to the DNA damage signals originating from short telomeres. Such cells are genetically unstable and have greatly increased ability to acquire genetic rearrangements that provide further growth advantages. The intricate involvement of telomeres in both aging and cancer ensures that pathways involving telomeres and telomerase will remain subject to intensive studies for many years to come.

Interestingly it appears that after reaching adulthood telomere length changes very little between different cells with different frequencies of replication (leukocytes, muscle, skin and fat) due solely to the influence of time passage.184 The difference in telomere length between these cells seems to occur during the first two decades of life creating an intra-individual synchrony among telomere length and cell types.185-188 For leukocytes it is thought that this two tiered telomere length behavior is born from the expansion of hematopoietic stem and hematopoietic progenitor cell pools.189

While it can be difficult to extrapolate it stands to reason that early symmetric stem cell divisions from the progenitor pool versus asymmetric divisions also define telomere length for the other cell types. Therefore, it seems that stem cell division among somatic tissues for maintenance purposes proceeds at similar rates in adults despite their inherent proliferation status. This information could prove useful because if there is a similar reduction of telomere length in various cell types for adults any treatment that increases telomerase concentrations and thereby increase telomeres will not have an imbalanced influence among various cell types. Basically there should not be a higher probability of developing cancer born from a specific cell type over another cell type.

In the age of genomic research a holy grail of sorts for aging would be to identify a single gene that has significant control over the aging process. In the pursuit of this goal along with a better understanding of aging in general numerous potential candidates have been researched among various model organisms and humans. As previously mentioned the Sir2 family of NAD+-dependent lysine deacetylases are viewed as a high quality genetic candidate for regulating aging due to its influence in extending the lifespan of numerous model organisms including C. elegans, yeast and Drosophila. In humans there are seven different Sir2 homologues (Sirtuins) most of which appear to also have influential roles in governing aging with SIRT1, SIRT2 and SIRT6 playing the most prominent roles. The reason for this prominence is that SIRT1 plays a role in metabolism and inflammation, SIRT2 plays a role in cell cycle and tumor development and SIRT6 plays a role in DNA repair, metabolism and TNFa secretion.190-192

SIRT1 is somewhat unique because it tends to become mobile in response to stress relocating to sites of DNA damage where it helps initiate DNA repair.193 However, this movement may increase the probability of gene expression that are enhanced during aging; basically increased stress can indirectly trigger changes in chromatin state due to SIRT1 influence.193 SIRT6 is an important positive element in promoting replicative capacity through maintaining telomeric chromatin.194 It also interacts with NF-kB subunit RelA as a form of negative feedback through the deacetylation of H3K9Ac to reduce NF-kB signaling.195-197 SIRT6 influence on aging may also involve reducing levels of insulin-like growth factor 1 (IGF-1).195 Finally note that because Sirtuins are dependent on NAD+, insufficient concentrations will result in reduced influence and increase aging potential.

Another popular area of aging study focuses on the relationship between aging and insulin interaction. Numerous studies in model organisms have demonstrated that increasing insulin sensitivity results in a significant increase in longevity.198-201 Not surprisingly though while the insulin receptor substrate (IRS)/PI3 kinase pathway influences aging in C. elegans and Drosophila in a rather straightforward manner, insulin pathways are more complicated in mammals with many more receptors thus elimination of insulin-like growth factor (IGF) and its respective receptors (IGFR) can result in perinatal lethality, diabetes, hyperlipidemia, obesity and liver dysfunction.198,201 Also the insulin/IGF-1 signaling (IIS) pathway in mammals has a strong interaction with growth hormones (GH), an element not utilized in non-mammalian model organisms, further complicating conclusions. Despite this increased complexity there is strong evidence that the IIS pathway does play a role in aging in mammals in that significant increases in average and maximal lifespan occur in mice with reduced plasma levels of IGF-1 and insulin.199-202

A study using Fat Insulin Receptor Knockout (FIRKO) mice further supported the idea that insulin signaling was important for longevity where despite having a normal appearance, appetite and fertility the knockouts had higher insulin sensitivity and less fat and outlived controls by 18%.203 This type of research also produced greater understanding behind a potential influencing mechanisms within the insulin pathway demonstrating that increased mitochondrial oxidative metabolism and white adipose tissue (WAT) metabolism play a role in FIRKO increased longevity.204 Unfortunately there is no specific understanding to how this increased metabolism influences inflammatory adipolines beyond the suspicion that there is a positive (increased anti-inflammatory) effect. Some point to adiponectin as a highly influential insulin sensitivity element that is derived from adiopocytes, but there is no definite evidence for the appropriate mechanism.205,206

The influence of IIS in aging is further supported by the detrimental effects of increased insulin resistance on lifespan and the positive effects of increased insulin sensitivity on lifespan. One of the more interesting real-world studies identified lower insulin resistance and more preserved beta cell function in centenarians versus other individuals who were only seventy to ninety years old.207 Some also link the increased life expectancy seen in calorie restricted diets to reduced plasma insulin levels and increased insulin sensitivity.208

While the influence of IIS in aging appears well supported,209,210 the currently understood involvement of GH is more controversial. Mice deficient in growth hormone like Ames dwarf, which do not secrete GH, prolactin or TSH, outlive controls by 35-70% dependant on other environmental factors.202,211 In addition GH receptor (GHR) knockout mice also demonstrated increased longevity.212,213 However, when GH antagonists are used to reduce GH signaling without a corresponding change in insulin levels there is no significant change in lifespan.213

Such a contradiction seems strange in that if GH signaling is eliminated through lack of substrate or lack of receptor then life is significantly extended, but if receptor activation is eliminated through antagonist binding life is not significantly extended. It stands to reason that despite the antagonist some GH does bind to the appropriate receptor initiating the GH pathway. This result seems to imply a very high initial sensitivity to GH binding that reaches activation saturation rather quickly. Think a Michaelis-Menten graph with a sharp initial slope. If this is true then it is difficult to conclude that increased longevity can be acquired through interaction with GH due to some of the negative effects associated with GH knockouts in humans.

The body types produced by GH or GHR knockout mice are somewhat interesting because they appear to have a lean body type whereas humans who suffer from Laron syndrome (the lack of GHRs) develop an obese body type due to increased fat and significant losses in bone density and muscle mass. While some studies have reported a loss of bone density in GHR knockouts this result does not explain the difference in fat content.214,215 From an evolutionary standpoint GH may be required to differentiate pre-adipocytes into adipocytes, a majority of which form white adipose tissue.216,217 Therefore, the loss of the GH pathway eliminates a principle formation pathway for white adipose tissue. However, GH has also been reported to be an important element in suppressing fat accumulation and increase muscle mass, a seemingly contradictory behavior.213

The explanation for this dual behavior is that during development GH is important in initiating the fat storage pathway and after maturity is used to regulate this pathway in a negative manner.213 This behavior is similar to the neurotransmitter GABA, which is excitatory during development and later becomes inhibitory in mature brains. Thus without white adipose tissue, more than likely the lean body type in Ames and GHR knockout mice is born from the development of brown fat and the increased use of lipids as a source of energy over carbohydrates reducing glucose production leading to suppression of gluconeogenesis and increasing insulin sensitivity.218-220 The reason that GH concentrations appear negative to aging is that aging is not advantageous from an evolutionary standpoint in that reproductive success is favored over longevity so rapid growth, early sexual maturation and strong levels of fertility, characteristics directly related to GH pathway activation, would be supported by evolution.

Another element that may support a role for insulin is that the development of hyperglycemia from high levels of insulin resistance appear to increase the synthesis rate of advanced glycation end products (AGEs) and glycation of proteins.198 AGEs typically form when reducing sugars react with carbohydrates and free amino groups and accumulate in structural proteins like elastin and collagen.221 However, there is no clear evidence that increased insulin resistance leads to increased synthesis of AGEs.

For those who have accepted the cause of aging to involve nutrient sensitive signaling elements like IGF-1 and mTOR the effect of these signaling mechanism induce aging through the facilitation of excessive macromolecule build-up within cells. The chief cause of this build-up is largely regarded as the decline in effectiveness and frequency of cellular autophagy removing damaged and unnecessary molecules and the continued expression of these nutrient sensitivity systems after their usefulness has ended.

Not surprisingly one analogy used to encapsulate this aging methodology, largely because it is used for numerous other things as well like global warming, is that of a bathtub with a running faucet. Think of IGF-1 and mTOR as the agents that control the faucet, autophagy as the drain and the amount of water in the tub being the biological age where too much water leads to flooding (i.e. death). If IGF-1 and mTOR expression exceed autophagy then an individual will experience biological aging as water fills the tub. Therefore, to accelerate aging one must either reduce autophagy or increase IGF-1 and/or mTOR expression; to decelerate aging one must increase autophagy or decrease IGF and/or mTOR expression. Proponents of this mindset believe that while ROS may induce genetic damage, cells die from an unbalanced growth/damage correction mechanism long before the genetic damage is sufficient to induce death.

If one is to believe this series of events then between the two treatment avenues enhancing or maintaining autophagy appears to be the superior one due to the negative side effects and quality of life elements associated with inhibiting mTOR or IGF-1/insulin interactions. Therefore, it may be a better strategy for individuals seeking an anti-aging therapy to focus on autophagy enhancement rather than further evaluating rapamycin or similar agents.

Finally one of the most robust and reproducible methods for positively altering lifespan is calorie restriction (CR) that excludes malnutrition or nutrient deprivation. CR is usually studied with non-control animals receiving a diet that is about 10-40% (normally 30% is standard) less caloric intake than control animals. CR-derived life expansion has been demonstrated in a variety of species including C. elegans, Drosophila and mice.222-225 Numerous rationalities have been hypothesized for why calorie restriction is able to achieve such success.

Supporters of ROS argue that reduced calorie consumption results in reduced metabolism and a reduced probability of synthesizing greater concentrations of ROS thereby extending life and youth due to less DNA damage, especially 8-OHdG damage.226-228 Supporters of insulin dependent aging argue that reduced calorie consumption results in a reduced concentration of circulating insulin and a reduced activation of the IIS pathway through IGF-1 binding thereby extending life and youth, although a reduction of protein is also required to achieve this particular effect.225,228-230 Supporters of NF-kB aging argue that CR down-regulates PI3K and AKT transcription which reduces NF-kB activation removing consistent activation of the “aging” phenotype.231 Others still think that CR influences mitochondrial biogenesis and recycling methods like autophagy to increase longevity.222,232 One of the chief benefits of CR is that there appears to be no age floor in which the methodology must start. Basically a 60-year old individual can begin a CR diet and still develop similar positive biological outcomes similar to that of a 40-year old on a CR diet for decades.

While there is significant evidence to suggest that CR plays an important role in influencing aging in various life forms there are some outstanding issues. First, CR has never definitely demonstrated lifespan extension in humans or non-human primates. In fact the one major concluded study that focused on non-human primates, the 1987 National Institute on Aging (NIA) study using rhesus monkeys reported improved health benefits and possible lower mortality rates, but no ceiling life extension.233 A University of Wisconsin study that started in 1989 that is also utilizing rhesus monkeys is still ongoing and has not released final conclusions, but has released studies in 2009 that concluded 13% of the CR group died from age-related causes versus 37% from the control group, which is in contrast to the NIA study.234 However, there are concerns that the diet fed to the controls in the Wisconsin study is too unhealthy (28.5% sucrose versus 3.9% for the NIA study) creating an inappropriate environment for comparison because the monkeys in the Wisconsin study were healthier simply from not eating the unhealthy diet not from the calorie restriction.235

Second, there are some significant drawbacks associated with CR in humans including reduced sex hormone production, reduced immune response, reduced muscle mass and lower bone mineral density.236-238 Whether or not the decrease in bone mineral density will increase the probability of fractures is unknown because bone quality appears retained despite this reduced mineral density.239 Note that all of these results are short-term, thus these issues could exacerbate with time or self-correct at a new type of homeostasis.

Third, the extension of ceiling lifespan in yeast utilizing a CR protocol relies on enhanced respiratory rates.240,241 This result may help support mitochondrial hormesis as an important element in the life extension effects of CR.242,243 However, hormesis is a somewhat controversial concept in biology, thus there is significant skepticism regarding its validity. This methodology could also tie into the reduction of ROS damage, but not on a reduced production level, but increased neutralization efficiency. This hormesis “priming” has some level of support in that induction of endogenous ROS production can extend life in some organisms.243-245 The change in methodology is unknown, but it may have some influence in increasing antioxidant efficiency.

Fourth, there are no good studies where CR is compared against a healthy Mediterranean type diet. Thus, the benefits from CR may be derived not from excluding calories, but from excluding “bad” calories. For example when one consumes additional calories those calories, to a point obviously, would not be negative if the appropriate vitamins and minerals are contained within maintaining a “nutrient/calorie” ratio relative to exercise level versus smaller calorie consumption strategies. This mindset also coincides with the idea that controls isolated solely to a laboratory are not effective wild-type mimics, thus the lifespan increases seen in CR organisms cannot be genuinely regarded as an increase versus wild-type organisms. Overall there is a lot of promise that CR restriction can be utilized as a means to reduce most of the negative age-related conditions, but whether or not CR is an effective means to extend ceiling lifespan is currently unknown because of these concerns.

With respects to anti-aging treatment, despite the positive results seen from treatments with rapamycin, the biggest problem with focusing on rapamycin as an anti-aging therapeutic is there are numerous side effects not simply those associated with immune system disruption. Not surprisingly rapamycin also induces metabolic alterations like hyperlipidemia, decreased insulin sensitivity (which should increase the probability for developing diabetes and may conflict with IGF-1 anti-aging) and glucose intolerance.246,247. Also there are questions regarding how it influences the gastrointestinal tract due to frequent diarrhea events in patients.248 While individuals suffering from illnesses like cancer and transplant recovery could look past these side effects, would it be responsible to expose healthy individuals to them?

Also most of the rapalogs (chemical agents that are derivatives of rapamycin) that have been developed to avoid or limit rapamycin side effects and/or increase pharmacokinetics for treatment like ridaforolimus, 32-deoxo-rapamycin, temsirolimus, etc. have significantly underpreformed relative to expectations both as anti-cancer agents and anti-aging agents.248 Some believe that these rapalogs focus too much on interacting with mTOR and have a lack of interaction with either PI3K or AKT, which facilitates the failure to properly mimic the biological effects of rapamycin.248

Of the numerous studies performed to investigate the causes of aging, a large amount of support has been developed for numerous different pathways. One of the key elements to developing a therapy is to define what is plausible and what is not. For example the expectation should not be to repair all damage incurred through aging because there will always be elements like epigenomic drift. While major players have been identified developing strategies to take advantage of this knowledge must be taken with caution, as shown above with rapalogs, because of the complexity and interactivity of the pathways involved and the natural aging aspect of organized life, which generates a progression towards random patterns of gene expression that may supercede pharmacological intervention.

Some of the key questions with establishing a lifespan extending methodology are as followed:

1) As discussed above there are numerous elements that are responsible for advancing biological age and it stands to reason that none of these elements as a standalone therapy will produce significant results. One might object to this statement citing significant life extension in various model organisms, but it is important to acknowledge that these gains are exclusive to these respective model organisms and as organisms increase in biological complexity the influence of these life extending changes wane as seen in studies of humans and non-human primates. For example genetic dampening of IIS in C. elegans increase average lifespan by 100%, in Drosophila by 25-30%, in mice by 20% and in non-human primates and humans <5%.249-252

2) There is significant overlap and relationship between cancer and various aging mechanisms where most of the mechanisms that appear to retard cancer formation induce aging; how will anti-aging therapies be reconciled with the possibility of higher rates of cancer?

3) There is a difference between extending ceiling/maximum lifespan and extending average lifespan. It can be rationalized that almost all life extension achieved by society throughout human history, the development of antibiotics, surgical procedures, better and balanced diets, etc., has been of the latter category; does human plasticity even allow for the extension of maximum lifespan and how could such a possibility be tested?

4) If maximum lifespan extension is achieved how will society manage the increased population, especially when most of the members of this population will consume more resources than they produce? Or will lifespan extension simply be a commercial industry that only the rich are able to utilize?

5) Clearly there are complexity issues that must be addressed for just because increasing the concentration of Compound A increases lifespan in C. elegans does not mean that increasing it in all situations will induce the same result. For example for the IIS pathway invertebrates have a single receptor that binds molecules that biologically represent insulin or IGF-1 and reducing binding efficiency leads to life extension. However, mammals have distinct specific receptor for binding both insulin and IGF-1 with different and overlapping function (IGF-1 controls growth and insulin controls metabolism). In addition mouse average lifespan is only increased when IIS is influenced in the right tissue with the right signaling elements because of coinciding requirements for an increase in insulin sensitivity. Similar complexity increases are seen in important longevity genes – FOXO and SIR(SIRT) where mammals have multiple genes per family that have a variety of influences.

Overall there are some key molecules that have an important role in aging. Of these molecules mTOR and NF-kB seem to govern youthfulness more than maximum lifespan while telomeres and ROS seem to have a greater influence on maximum lifespan. Therefore, society must develop a strategy to address both of these influencing categories otherwise life extension will either not be plausible or will be a rather torturous experience of extended old age. Also the balance between these categories must be considered in their interaction and consequence. For example with the rise of antibiotic resistant pathogens the loss of immune system functionality to increase youthful lifespan of cells does not appear to be a beneficial tradeoff for individuals or society, thus both mTOR and NF-kB strategies must be carefully studied and applied. However, between the two a pursuit of a NF-kB neutralizing treatment appears to be the better strategy.




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