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I. The Importance of Aging Research
II. Pitfalls and the Current State of Life Extension Research
III. Moving Forward with Life Extension Research

I. The Importance of Aging Research

The Cost of Aging
Aging is expensive, both emotionally and socioeconomically. It is the leading cause of disability and death in developed countries, and age-associated diseases are estimated to be the cause of 85% of deaths (Cutler, 2006; CDC, National Vital Statistic Reports, 2006). The elderly relatedly consume the majority of healthcare costs, and the world population of those over 80 years old is expected to increase over 400% between now and 2050. This translates into a much greater demand for healthcare that will put significant stress on worldwide healthcare systems in developed countries. This will undoubtedly be compounded with existing healthcare problems, where some elderly forgo meals to pay for expensive medications they consider more basic necessities.

In addition to the predicted vast expansion of the elderly population, most of the treatments for age-associated diseases that this population will increasingly seek will be palliative at best. Age-associated conditions such as metastasized cancer, metabolic syndromes, multiple neuropathologies, and advanced cardiovascular disease cannot be reversed by any present-day technology. Instead, existing treatments for these diseases strive to attenuate the pathologies' effects in order to give the afflicted a bit more healthy life. Therefore, with no cure for these diseases, a significant segment of the population undergoes continual, expensive, and often merely palliative treatments for the duration of their lifespans.

If there existed methods to effectively treat or seriously attenuate these age-associated pathologies, manifest in the extension of healthy longevity and the offsetting and reduction of time that older individuals spend in degenerative states before death (compression of age-associated morbidity; squaring of the population's mortality curve), it would greatly reduce the impending socioeconomic burden upon society (Fries, 2003). Additionally, even if morbidity were not compressed, it would be more financially prudent to spend money currently allocated to the many palliative treatments for age-associated diseases on efficacious treatments that could more likely result from investment in attenuating the mechanisms of aging.

Disease Research vs. Aging Research
The Vitae Institute believes that basic research into how to extend health and longevity in humans is the most promising vehicle for bringing about positive changes in the treatment of age-associated pathologies. Despite the millions of dollars spent on attempting to find cures for specific age-associated diseases, the majority of this funding does not significantly improve quality of life nor significantly alter survival data. One might ask "we're already spending billions on ways to cure various age-associated pathologies, why spend money on 'aging research'?" Curing cancer, for example, tomorrow would only increase average longevity by a few years; partially curing a class of diseases, such as cardiovascular diseases, would similarly yield only a small increase in average life expectancy (Tsai, 1978). But clinically addressing the underlying mechanisms of aging has the potential of extending average and maximum longevity by much more. Because as people age their probability of becoming afflicted with many possible age-associated pathologies steadily increases, if you cure one or a few of their most pressing ailments you are only delaying their development of another age-associated pathology that will soon thereafter claim their life (Cutler, 2006). On the other hand, if you are able to attenuate physiologic processes that give rise to many of the pathologies associated with aging, then you can in theory bring about a much more beneficial clinical result of both increased lifespan and quality of life. Obviously, this is no simple task and is predicated on the hypothesis that multiple age-associated diseases have common causes, but we have the technological potential to address the former and evidence supporting the latter, as is subsequently discussed. The only way to approach this hypothesis and intelligently attempt developing efficacious therapies for age-ass! ociated pathologies, is to form a better understanding of the fundamental mechanisms of aging (Holliday, 1997).

The public's awareness of and relation to specific age-associated diseases is extremely amenable to the establishment of research centers, non-profit initiatives, and fundraising in general. Aging research, in contrast, does not possess this same impetus. Taking into account the possible benefits that it could afford, the amount of money and effort put into it seems comparatively highly askew. One does not have to look to far to see why this is not surprising though; families see their elder members with "Alzheimer's", "cancer" and "heart disease" instead of manifestations of underlying age-associated changes, and vote and donate money accordingly. Only through intelligent basic research and cogent public education on the relationship between age-associated diseases and the putative mechanisms of aging that underlie them will these age-associated diseases be aptly treated and cured (Holliday, 1997).

Urgency of Getting Basic Aging Research Done
The Vitae Institute approaches aging research with a great sense of urgency to advance our understanding of the mechanisms of aging. This is because we see aging research not as an end in itself, but merely as a means of advancing an understanding of aging to clinical utility in the form of life-extension technology and the associated amelioration of suffering from age-associated pathologies. We accept that the goal of significant life-extension technology is arduous and ambitious, but that only extreme dedication to it and adherence to scientific principles will lead to its realization, no matter how long this may take. Put in this perspective, more dilly-dallying now, with regard to the pace and efficiency of aging research, will entail more lives lost to lack of adequate technology. If there is any chance that technology could be implemented in our lifetime to increase our longevity, then spending resources developing this technology now could also have a massive impact on the duration and quality of our lives. The success of this technology would lead to: 1) lessening the socioeconomic impact of an increasingly aged global society, 2) the saving, essentially, of multitudes of lives, and 3) realizing the long-standing aspiration of significantly extending human longevity. The Vitae Institute feels the same urgency for carrying out aging research that many individuals and companies express with regard to finding cures for many age-associated diseases like certain forms of cancer and various neuropathologies, except that this urgency is all that more poignant due to the fact that far less money is being spent on basic aging research, and the rewards could translate into effective treatments for a much wider host of presently incurable conditions. While it is impossible to predict when breakthroughs will occur in aging research, it is certain that the more money and effort we efficiently spend on it now, the sooner life-extension technology will be developed.

Scientific Rigor in an Endeavor where Snakeoil is the Predominant Precedent
Our historical roots are replete with tales of the aging process being capable of being tamed: from the Epic of Gilgamesh, Ponce de Leon's fountain of youth, biblical supercentenarians, and Osiris's reanimation in Egyptian mythology, to contemporary representations of immortality in vampirism and movies such as Highlander. While entertaining as well as philosophically and historically interesting, such examples most often do little to help the public view the aging process as something to be reasonably addressed in the scientific sphere. This tainted image of aging research being overly fanciful in the eyes of the public and scientists is compounded with the populace's gullibility with regard to the same old snakeoil products being rebranded as contemporary "anti-aging" supplements. None of these supplements or related therapies have proven efficacy with regard to attenuating the aging process. (Olshansky et al., 2002) There is therefore an understandable apprehension towards anyone purporting to indulge in research aimed at attenuating the aging process because, historically, such claims dwelled exclusively within the domains of mysticism and quackery. Even today, many scientists occupy the shoes of their snake-oil predecessors in exaggerating the importance of research findings while failing to pursue the questions most worth answering--those leading to a practical understanding of the aging process.

Aspirations to Life-Extension: Neither a Pipe Dream nor that Radical
Not only does basic aging research hold much promise for addressing the multitude of age-associated pathologies, but it also constitutes an approach to eventually realizing the long-standing dream of reversing the aging process and significantly extending human longevity. Although still regarded widely as a pipe dream, the difference between contemporary medicine and significant life-extension technology is simply a matter of scale. When the latter is put in the proper context it is not a radical notion, but rather a rational outgrowth of mainstream medicine. Progressive biogerontologists aspire simply to accomplish what mainstream medicine does today: keep people healthy and alive longer. And today scientists are much better equipped technically to methodically investigate life-extension and the underlying etiology of aging compared to our ancestors possessing similar ambitions.

It is impossible, given our present ignorance with regard to the mechanisms of aging, to predict the breakthroughs that will lead to life-extension technology, or when they will occur. But this in no way implies that such breakthroughs are impossible! On the contrary, there is a significant amount of evidence supporting the possibility of life-extension. Many genetic mutations in model organisms exhibit replicable extensions in both mean and maximum longevity (Yang and Wilson, 1999; Guarente and Kenyon, 2000). Using artificial selection, scientists have similarly extended the lifespan of model organisms in the creation of long-lived strains. (Arking, 1987) Additionally, caloric restriction extends longevity and retards age-associated diseases in many species (Heilbronn and Ravussin, 2003; Weindruch and Sohal, 1997), and seems to have beneficial physiologic effects in some small human studies (Heilbronn et al., 2006; Meyer et al., 2006; Fontana, 2004). All of these data are in harmony with evolutionary biology and suggest that healthy lifespan, as well as both the mean and maximum longevity in a population, is mutable. The question is not whether life-extension technologies are attainable, but rather how can we today make progress in their development and subsequent application to other age-associated pathologies that we strive so hard to treat today.

II. Pitfalls and the Current State of Life Extension Research

Aging is Not Programmed: It's what Genetics Doesn't Do
Aging is in absolutely no way programmed. There are no such things as "aging genes" or "aging pathways" (Kirkwood, 2002). It is not what genetics does, but rather what genetics fails to do that manifests aging.

Confusion regarding the idea that genes in no way regulate aging arises primarily from the following: 1) the genes of an organism obviously influence their longevity (eg. humans live longer than mice, extreme longevity can be hereditary) and 2) mutations in genes involved in various homeostatic mechanisms can extend or attenuate lifespan in model organisms (Yang and Wilson, 1999; Guarente and Kenyon, 2000). However, it is extraordinarily fallacious to assume, simply because genetics can influence longevity and the rate of aging, that these genetic elements represent facets of programmed aging (resulting in them being called "aging genes" or "aging pathways" by some) and that the mechanisms of aging are in some way evolutionarily adaptive. Evidence from the field of evolutionary biology precludes the latter, as has been aptly summarized elsewhere. (Kirkwood, 2002).

This distinction between influencing and programming aging is crucial when determining the fruitfulness of different pathways for aging research. This distinction can be confused by scientists stating that certain genes or pathways regulate aging, sometimes implying influence and other times implying programming. Subscription to this fallacy that aging is genetically programmed is still quite pervasive in both the general population and the sciences. When scientists, investors, and policy-makers believe this archaic idea, it leads to significant amounts of time and money being spent on experiments that will contribute nothing to a cohesive understanding of aging or to ways to combat it. This time and money could be better spent on more scientifically valid research, and therefore this errant belief in programmed aging constitutes a significant obstacle in forwarding legitimate basic aging research.

Limitations of Modulating Endogenous Pathways
Many scientists are today studying the genes that, when modified, increase average and maximum longevity (influencing aging) of the model organisms that contain them. These experiments are useful in demonstrating the mutability of the aging process, but do little to elucidate the mechanisms of aging or to benefit the health of humans. For the sake of example, let it be said that a gene is discovered that, when mutated extends the lifespan of the mouse by 30%; its human allele equivalent is known to be associated with long life, and that basic research has established that possession of the gene leads to increased longevity via attenuating free radical damage associated with normal mitochondrial metabolism. What could be done with this information to benefit the aging patient? Gene therapy or pharmacological targeting of the gene pathway, if possible, would likely not benefit an aging patient if the damage has already been done.

How much benefit does slowing down the aging process have if the mechanisms of aging have already unfolded their inadvertent payload of damage? The primary utility of any such studies is that they better characterize processes involved with the mechanisms of aging and age-associated damage. But does this characterization warrant the millions of dollars that are spent on the aforementioned identification and characterization of so-called "gerontogenes" that extend longevity? If there are ways to directly measure age-associated damage and hypothetical mechanisms of aging, and this could lead to the attenuation of these processes, why not cut to the chase?

Very Dubious that a Magic Pill Will Make You Live Forever
All of the little that is known about the mechanism of aging indicates that no simple pharmacological intervention will be effective in reversing them. Even if the effects of caloric restriction could be emulated by a drug in humans, this pathway of life-extension research has drawbacks: 1) it doesn't necessarily elucidate the mechanisms of aging or damage associated with them (which would be useful for developing further life-extension therapies), 2) although there are promising reports for CR improving health in small human experiments, it is uncertain whether it will significantly extend longevity, 3) there will be a definite limit to the ability of CR to extend life because at best it is slowing down the mechanisms of aging rather than reversing them. These criticisms apply equally to other so-called "anti-aging" drugs. Despite these drawbacks to such research, it appears often easier to get grants for research that will allow you to identify pharmaceutical targets even if those pharmaceutical targets do nothing for the pathologies one is investigating! It is likely that significant life extension will only be accomplished with a series of therapies that take into account the currently unknown mechanisms of aging and the damage associated with them. Although this research pathway may be arduous, it is definitely easier than rummaging in the dark for non-existent "aging pathways."

Current State of Federal Life-Extension Research in USA
The National Institute on Aging had an estimated budget for 2006 of 1.06 billion dollars. Most of this research is directed towards geriatric research and developing treatment for specific diseases. A part of the funding is devoted to the "biology of aging" and a subdivision of that to "extending the lifespan." However, the prime focus of this latter portion is directed towards the genetics of longevity, and to some extent the pharmacological emulation of CR, which via previous descriptions, are not efficient and reasonable means of developing a cohesive understanding of the aging process or means to attenuate it.

Specifically, under the heading "life extension" the NIA lists three activities: studying genes associated with extreme longevity in humans, developing assays with the fruit fly for evaluating the effect of genetic mutations and pharmacological agents on longevity, and the ability of a class of compounds called sirtuins to putatively emulate the effects of caloric restriction. Reiterating points made previously, performing the following: 1) studying the genetics of longevity, 2) trying to find simple pharmaceutical targets related to aging, and 3) attempting to use pathways associated with caloric restriction; all of these endeavors do not necessarily forward any understanding of the damage constituting the mechanisms of aging, nor how to slow or reverse aging.

The government can obviously not abandon geriatric patients, and whether or not basic aging research will ever help them is irrelevant to their need for basic medical care now. However, while funding for basic geriatric medical care is blatantly warranted, funding the three previously described research projects with the purported purpose of lengthening the lives of a populace increasingly dependent upon geriatric medicine is insultingly misleading to all tax-paying citizens. The extraordinarily limited and ungrounded scope of this research for life-extension purposes will only benefit the aged out of pure accident, and it is serving as a substitute for more legitimate aging research that could, if more adequately funded, expedite a better understanding of the aging process and the development of life-extension therapies.

Current State of Private Life-Extension Research
Compared with public sector research, the private sector unfortunately does not have much more to offer with regard to quality aging research. Aside from a few enterprises, private endeavors actually allow much more leeway for scam artists, archaic or nonsensical theories, and in general scientifically invalid profiteering substituting for legitimate research.

Multiple private organizations suggest that the mechanisms and damage associated with aging, as well as means to reverse them are known. They request funding to simply carry out these means to have their investors and the world reap their rewards. On one hand this could lead to legitimate research that serves to validate or invalidate the various hypotheses, presented falsely as facts, that they employ in such endeavors. On the other hand, the false assertion that the damage associated with aging and the means to fix it are known is inarguably damaging to efficiently developing a cohesive and practical understanding of the aging process.

More less-specialized organizations spend great sums of money searching for cures for specific age-related diseases. As mentioned before, such cures, if found, might benefit those suffering the symptoms of those specific diseases, but the relief from such cures would only serve as a brief reprieve before cured individuals would be assailed by another uncured age-associated ailment.

Aside from the Vitae Institute there are very few non-profit organizations that employ both skepticism and open-mindedness for the scientific investigation of the mechanisms of aging.

III. Moving Forward with Life Extension Research

Contemporary Understandings of the Aging Process
At present scientists have many hypotheses regarding the underlying mechanisms of aging, some with significant experimental support. Many support the idea that the mechanisms of aging are very multi-faceted, and that many fundamental aspects of physiology break down to manifest the propensity for developing age-associated pathologies (Holliday, 1997). However, the relative contribution of the various hypotheses of aging to actual unfolding of the mechanisms of aging, whatever they may be, is at present unknown. Of many hypotheses regarding the mechanisms of aging, including: telomere shortening, cellular aggregate accumulation, DNA damage, free radical damage, etc.; not one of these phenomena has experimental support enough to substantiate it as causal in the etiology of aging. Despite this, many authors present hypothetical catalysts of aging as sole causal agents of aging, based upon indirect and insufficient experimental evidence. These related hypotheses are extraordinarily useful as theoretical models for exploring the still-uncharted territory of the aging process, but presented as established fact also often give laypeople a false sense that scientists know more about the aging process than they actually do.

Interdisciplinary Nature of Life-Extension Research
The breadth of sciences necessitated in a comprehensive investigation of the mechanisms of aging and development of life-extension technology is extraordinary. In addition to many distinct subfields of biology, many different fields are useful for forwarding such an investigation. Examples include: chemistry (eg. understanding what types of intracellular metabolic side reactions occur with senescence), engineering (eg. development of devices and vectors to ameliorate age-associated damage), and medicine (eg. characterization of age-associated pathologies, evaluation of putative interventions' efficacies). These are just a few among many examples of disciplines and associated topics of investigation. To formulate and carry out a reasonable approach to understanding aging mechanisms and developing life-extension technology, a much more interdisciplinary approach than what is currently being endorsed by most public and much private funding will be utterly requisite.

Open-Minded About Progressive Research Avenues
Given the consideration of illuminating the mechanisms of aging as a pragmatic clinically-relevant enterprise with a great sense of urgency, rather than as an abstract and un-pressured academic endeavor, as well as the utter lack of knowledge concerning the specific mechanisms of aging, the Vitae Institute is prepared to entertain creative and novel approaches to bettering an understanding of the aging process and ways to attenuate it. We believe that thorough consideration of such progressive research approaches, so long as they maintain the aforementioned scientific validity and methodological stringency, will lend to more efficiently realizing the eventual development of life-extension technology.

Objections to Life-Extension and the Status Quo
While many scientists have properly addressed objections to attenuating the aging process elsewhere, it is useful to state that most of these objections are as applicable to contemporary medical practices as they are to life-extension technologies. Arguments against life-extension technologies (eg. they are unnatural or unholy, they will contribute to class disparities, they will lead to overpopulation) apply just as well to facets of modern medicine, such as the use of antibiotics, defibrillation, and organ transplantation. As has been stated, the fundamental logic of pursuing the development of life-extension technologies is indistinct from that which sustains the contemporary medical status quo: keep people healthy, alive and happy for longer. Therefore, we believe that no ethical concessions need be made in pursuing the development of life-extension technology.

What Type of Research Should Be Done?
Though it is unknown how the specific mechanisms of aging unfold, many theories have accumulated significant supporting evidence over the past few decades as being implicated in the etiology of aging and multiple age-associated pathologies. Examples of these include mitochondrial dysfunction, DNA damage, and cellular aggregate accumulation. Further experimentation in elucidating their role in the aging process and into methods of attenuating their progression could expedite translational research for the treatment of age-associated pathologies far more efficiently than disease-specific research, for reasons mentioned previously. The most convincing experiments that could be performed in evaluating whether or not these processes are causal in the aging process would be establishing that their reversal results in increased lifespan and the attenuation or reversal of the few existing biomarkers for aging. To date, few labs are performing this type of research and few, if any, government grants are sponsoring it. This is the type of research that the Vitae Institute was formed to endorse.

The Vitae Institute
The Vitae Institute was formed in order to stimulate research into ascertaining how the mechanisms of aging unfold and to exploit any promising results of these experiments to attenuate or reverse these mechanisms in humans to extend healthy lifespan. Please see the goals and projects section of this website to learn more about how the Vitae Institute will it will accomplish this. Also, note that this page will be periodically updated with revisions and new information.