Interview
with Dr. Leonid A. Gavrilov, Ph. D.

This is an original transcript of the interview with Dr. Leonid A. Gavrilov, Ph. D.  The edited and abridged version of this interview is published in the scientific peer-reviewed Journal of Anti-Aging Medicine:

"PIECES OF THE PUZZLE. An Interview with Leonid A. Gavrilov, Ph.D."
Journal of Anti-Aging Medicine, 2002, 5(3): 255-263. 
Interview (pdf file)
http://www.catchword.com/titles/10945458.htm
 

Question 1:
Dr. Gavrilov, what is your background and how did you become interested in studying aging and longevity?

I have Master degree in chemistry (chemical kinetics and enzymology) and a Ph.D. in biology (genetics), both from Moscow State  University, Russia.

Then I spent a decade of  intensive research and self-education, writing a book "The Biology of Life Span", which was published in the United States in 1991.

While working on this book I really tried to understand what is aging, and why are we aging and dying.

So, I had to make an extensive and critical review of an abundant scientific literature on aging and longevity, trying to reconcile different findings and theories.

I also collected and analyzed thousands of life tables (lifespan survival data) for different human populations and other biological species. It was a tremendous amount of work that has been done in collaboration with Dr. Natalia Gavrilova (my wife).  We were fortunate to make a number of new findings, which are cited now in scientific literature.

Writing a book was a good way of self-education in aging studies. How do I know that this self-education was correct?  Well, there are some indicators. For example our book is selected and cited by the "Encyclopaedia Britannica" as recommended reference on longevity topic. This book also received positive reviews published in a dozen of scientific journals, including Nature, British Medical Journal, BioEssays etc, and over a hundred of citations in scientific literature. So, perhaps our research and self-education efforts were not in vain.

Five years ago we immigrated in the United States from Russia, and it was another very good test for our scientific credentials, when we applied for research funding in this new and highly competitive environment. We were lucky to be awarded with research grants from the National Institute on Aging, NIH, to study a familial transmission of human longevity, and the parental age effects (effects of parental age at person's conception on person's lifespan).

So,  we managed to continue our research work and professional publications on human longevity in this new,  highly competitive environment. Perhaps it is somewhat ironic that my scientific background is now featured  in "Who's Who in America", Marquis Who's Who edition, despite I am still a citizen of Russia.

More information on my scientific background is available at our website "Unraveling the Secrets of Human Longevity" at:
http://longevity-science.org/

Well, this is the answer to the first part of your question regarding my scientific background. The answer to the second part of your question how I became interested in studying aging and longevity research will be much shorter and perhaps more funny.

The decision to study aging was made early in my life, when the school years were coming to the end, and the question has become urgent what should I do next.  I had an idealistic mind at that time and  I have read a lot of science fiction. So, I thought that perhaps the only way to succeed in really worthwhile projects (such as understanding of how human brain thinks, or  deep exploration of space) is to have enough time to accomplish them. Thus I decided to start with aging problem in order to overcome the time constrains, just as a prelude for more interesting stuff...   I also thought that in order to be able to understand the aging chemistry and to make an anti-aging drug, I should  first start as an university student at the department of Chemistry.

 Is not this funny?  May be, but I do not regret of my decisions.

I received a free but rather good initial education at the Department of Chemical Kinetics, founded by the Nobel laureate Nicolai Semyonov  - a famous discoverer of free radical chain reactions. So, the free-radical theory of aging and the mechanisms of damage protection by antioxidants became familiar to me in the very beginning of my scientific career.

I was also very much impressed by the power of quantitative approach in science -- it is really amazing that it is possible to discriminate between intricate competing mechanisms (hypotheses) of chemical reactions, just analyzing quantitatively the exact time trajectories (kinetics) for concentrations of reaction components and the products.  My immediate thought was that perhaps a similar quantitative approach could be applied to the biological aging problem -- to uncover the mechanisms of aging through quantitative analysis of age-related mortality kinetics.

It was this scientific idea of quantitative analysis, which shaped all my further research efforts. An appreciation of a great power of quantitative approach was reinforced by my further education and research work for Ph.D. in genetics.   It is really amazing that the very idea of genes, their existence in pairs (alleles), their random and independent segregation in offspring, and the idea of dominance -- all this came to Gregor Mendel as a result of his thoughtful quantitative analysis of  simple observations on trait frequencies in parents and offspring. Later this purely quantitative approach to the analysis of trait frequencies also allowed the Nobel laureate  Thomas Hunt Morgan to find out that genes are organized in groups in a linear fashion ( in chromosomes), to make the gene maps and to discover the crossing-over  phenomenon. Finally another Nobel laureate, Barbara McClintock discovered the phenomenon of genetic instability and "jumping genes" (transposons), just through a quantitative analysis of simple observations on color variation among kernels of maize !

I find a special charm in these elegant studies, where great scientific discoveries are made just through a clever quantitative analysis of  very simple observations, rather then fancy and expensive cutting-edge techniques. These historical examples convinced me in the very beginning of my scientific carrier that the most powerful scientific instrument is still a human brain.

So, all my further research work was made in this tradition of placing the main emphasis on human scientific intelligence. This quantitative approach can be summarized by the following motto: "think, measure and count; count, measure and think."  This is why the full title of our book is not just "The Biology of Life Span", but rather "The Biology of Life Span: A Quantitative Approach."  The quantitative approach became a cornerstone of all our scientific studies.
 

Question 2:
Please describe your current position and your scientific responsibilities

I am a fortunate recipient (Principal Investigator) of the Independent Scientist Award from the National Institute on Aging, NIH, which provides me with 5 years of protected time for research on aging and longevity.

My scientific responsibility (as I understand it) is to do a good science and to publish new relevant findings in good scientific peer-reviewed journals.  For example, recently we have developed and published a new unifying theory of aging and longevity based on reliability approach. This new theory provides a general explanation of aging for organisms as well as for  technical devices. It was published by the Journal of Theoretical Biology and received media attention, including "The Scientist" journal.

I also developed a course  "Biodemography of Human Mortality and Longevity,"  which I teach at the University of Chicago. Teaching activities are very useful for scientific research, because they stimulate to clarify scientific issues for students to the extent, when you begin to understand them yourself.  For example, our recent scientific article "Evolutionary Theories of Aging and Longevity" was written and published largely thanks to teaching activities.

I am fortunate to work at the Center on Aging, NORC/ University of Chicago with so stimulating working environment that I usually forget about time until it is really too late ( usually 1-2 a.m. including weekends).

In other words, I am really happy with my work except that the first year of my 5-year grant has already gone...
 

Question 3:
In your view, what is aging, how does it occur, and how does it express itself in human clinical disease?

Aging is a summary term for a set of processes, which contribute to health deterioration and ultimately to death with the passage of time (calendar age).

In other words any process, which contributes to age-related decline in performance, productivity and health is a component of the aging process that deserves our attention and intervention.

You can think of aging as a group of processes responsible for such manifestations as increasing risk of  frailty, disability, morbidity (for age-related degenerative diseases in particular)  and ultimately increasing mortality rates.

This interpretation of aging is consistent with general definition of aging system in mathematical reliability theory and reliability engineering as a system demonstrating age-dependent increase in failure rates.  Failure is such an outcome when the system deviates from optimistically anticipated and desired behavior ("fails").

The main problem with studying aging is that it is the many-headed monster, with many types of failures and often with multiple failures. Therefore an attempt to describe this complex multidimensional phenomenon through the change of just one index  -- dubbed as "biological age", or "physiological age", or "real age" may be a misleading and even a deceptive oversimplification. More adequate scientific language to describe the aging phenomenon could be found in general system theory and in reliability theory in particular.

Interestingly, the reliability theory predicts that a system may deteriorate with age even if it is built from non-aging elements with constant failure rate. The key issue here is the system's redundancy for irreplaceable elements, which is responsible for the aging phenomenon. In other words, each particular step of system destruction/deterioration may seem to be apparently random (no aging, just occasional failure by chance), but if a system failure requires a sequence of several such steps (not just a single step of destruction), then system as a whole may have an aging behavior.

Why is this important?  Because the significance of beneficial anti-aging interventions is often undermined by claims that these interventions are not proven to delay the process of aging itself, but instead that they simply delay or "cover-up" some particular manifestations of aging.

In contrast to these pessimistic views, the reliability theory says that there may be no specific underlying elementary "aging process itself" -- instead aging may be largely a property of  redundant system as a whole, because it has a network of destruction pathways each being associated with particular manifestations of aging (types of failure). Therefore, we should not be discouraged by only partial success of each particular anti-aging intervention, but instead we can appreciate an idea that we do have so many opportunities to oppose aging in numerous different ways.

Thus, the efforts to understand the routes and the early stages of age-related degenerative diseases should not be discarded as irrelevant to understanding of the "true biological aging".   On the contrary, the attempts to build a Berlin wall between biogerontology and clinical medicine are counterproductive. After all, the main reason why people are really concerned about aging is because it is related to health deterioration and increased morbidity. The most important pathways of age changes are those that make older people sick.
 

Question 4:
How has the scientific community's view of aging in general evolved in recent years?
Is there a consensus on what aging is and how it occurs?
What are the most important controversies in the field at present?

The views on aging have changed dramatically. They also have become more diverse and polarized in recent years.

Just a decade ago there was almost a consensus to consider aging as irreversible, universal and intrinsic process. Also aging was often considered as an immutable fundamental process, so that little could be done about it.  For example, there was a belief that mutations can only shorten the lifespan, not to increase it.  And even if some mutants lived longer lives, the suggestion was that this comes with the cost of crippled life.  Aging was considered as generalized deterioration, and, therefore, the search for specific interventions with very large positive effects on lifespan was considered a completely futile task, destined for failure for fundamental  reasons (see below). There was also a belief that each biological species has a specific maximal lifespan, which is immutable within a given species.

We remember well the 1980s, when we first challenged the concept of species-specific maximal lifespan, argued that there is no  fixed limit to longevity, and even suggested a reliability theory of aging predicting late-life mortality deceleration and levelling-off. The debates were hot, and only after publication of our book in 1991 our arguments were taken seriously.

Now we are pleased to observe that the idea of fixed maximal lifespan limit is rejected by many other researches, and that there is a real fuss now over late-life mortality deceleration, which was described and explained in our book. The idea of immutability of aging is also challenged now in professional scientific journals.

Aging studies are now in the state of paradigm shift, or frankly speaking,  a scientific revolution. Controversies are inevitable in such transition periods and they do indeed exist.

The most important current controversy is related to evolutionary explanation of aging. Evolutionary biologists were always very generous with gerontologists in providing advice and guidance on how to do aging research “in directions that are likely to be fruitful”. Surprisingly, this generous intellectual assistance proved to be extremely injurious for aging studies. This happened because evolutionary theory was interpreted in such a way that the search for single-gene mutations (or life-extending interventions) with very large positive effects on lifespan was considered a completely futile task, destined for failure for fundamental evolutionary reasons. Researchers were convinced by the forceful evolutionary arguments of George Williams that “…natural selection will always be in greatest opposition to the decline of the most senescence-prone system” and, therefore:

“Senescence should always be a generalized deterioration, and never due largely to changes in a single system.…This conclusion banishes the 'fountain of youth' to the limbo of scientific impossibilities where other human aspirations, like the perpetual motion machine and Laplace's 'superman' have already been placed by other theoretical considerations. Such conclusions are always disappointing, but they have the desirable consequence of channeling research in directions that are likely to be fruitful.” [Williams, G.C. (1957) Pleiotropy, natural selection and the evolution of senescence. Evolution 11, 398­411].

As a result of this triumphant evolutionary indoctrination, many exciting research opportunities for lifespan extension were squandered for half a century until the recent and astonishing discovery of single-gene mutants with profoundly extended longevity was ultimately made, despite all discouraging predictions and warnings based on evolutionary arguments.

Recent discoveries of lifespan-extending mutations are spectacular. A single-gene mutation (daf-2) more than doubles the lifespan of nematodes, keeping them active, fully fertile (contrary to predictions of some evolutionary theories), and having normal metabolic rates. Another single-gene mutation, called methuselah, extends the average lifespan of fruitflies by about 35%, enhancing also their resistance to various forms of stress, including starvation, high temperature, and toxic chemicals. Finally, a single-gene mutation was found in mice extending their lifespans by about 30% and also increasing their resistance to toxic chemicals.

Researchers involved in these studies came to the following conclusion: “The field of ageing research has been completely transformed in the past decade.…When single genes are changed, animals that should be old stay young. In humans, these mutants would be analogous to a ninety year old who looks and feels forty-five. On this basis we begin to think of ageing as a disease that can be cured, or at least postponed.…The field of ageing is beginning to explode, because so many are so excited about the prospect of searching for — and finding — the causes of ageing, and maybe even the fountain of youth itself.” [Guarente, L. and Kenyon, C. (2000) Genetic pathways that regulate ageing in model organisms. Nature 408, 255­262].

Now, when the single-gene life-extending mutations have been found, evolutionary biologists are presented with the task of reconciling these new discoveries with their theories.  However, gerontologists will also have to learn a lesson from the damage caused by decades of misguided research, when the search for major life-extending mutations and other life-extension interventions was equated by evolutionary biologists to a construction of perpetual motion machine.

Thus, we do really live in an interesting time, when new ideas about aging are coming!
 

Question 5:
Can aging be altered, and if so, how might we intervene?

Well, my answer to this question may be rather unusual and therefore it may require a detailed justification.

Human aging seems to be already altered dramatically in developed countries over the last 50 years, although these significant changes are not yet completely understood and appreciated both by the scientific community and by the public.

This remarkable shift in human aging schedule is largely overlooked by researchers and society, because these historical changes were  too slow and gradual for human perception (like historical  changes in human development schedule known in anthropology as 'acceleration' phenomenon), and we still do not understand exactly why and how it happens.

Now, let me provide some justification, why should we question and perhaps reconsider the conventional idea of immutability of human aging.

The idea of aging immutability was supported in the past by demographic observations that increase in human life expectancy was caused mainly by preventing deaths at young ages, while death rates at older ages (say, above age 80) remained surprisingly stable. This concept is known in demography as 'rectangularization of the survival curve'  -- because the survival curve (numbers of survivors as a function of age) evolved in history towards more rectangular shape.  According to this concept we were evolving to the society with very few deaths at younger ages, and 'compression of mortality'  at older ages, as more people survive to the maximal possible human lifespan. This fixed biological limit to human longevity was believed to be determined by the immutable aging process.

In 1985, we challenged this conventional concept in our study "A new trend in human mortality decline: Derectangularization of the survival curve" published by the Journal of American Aging Association (Age, 1985, v. 8, p.93). Specifically, we discovered a new trend in mortality decline in developed countries like Sweden after 1950s -- preferential and accelerating decrease in death rates among particularly old people. This paradoxical observation was later published in a more elaborated form in our book in 1991.

These findings challenged the existing scientific paradigm of aging immutability, and therefore they experienced several steps of denial. First,  these findings were just ignored as if they did not exist, then the doubts were cast over the data quality for the oldest-old mortality. Finally, when the unprecedented historical decline in the oldest-old mortality rates could be no longer ignored or disputed,  the claims were made that it is not related to changes in human aging, but instead represents the undesired consequences of medical success in sustaining life, as more and more people are kept alive by artificial means in greatly debilitated and degraded conditions.

The key issue here is that not only the death rates start to decline preferentially among the oldest-age groups, but that their health status (within the same age group) has been improved significantly over time.  Thus, the time schedule for aging manifestations has been dramatically altered over the last 50 years in developed countries, and this fortunate trend seems to accelerate over time.

If human aging is already altered, then next question is - why does it happen?   I wish I know the answer to this question, however there are some plausible working hypotheses to explore.

Aging retardation may be partially related to a better nutrition among later historical birth cohorts -- early-life nutrition history is in fact a very serious matter because a trivial deficiency in micronutrients (i.e. vitamins etc) has the same devastating impact on DNA integrity as ionizing radiation (findings of Professor Bruce Ames at Berkeley). People are terrified by the threads of radioactive pollution, yet they receive much more damage to their  DNA from a trivial micronutrient deficiencies. There was a remarkable improvement in vitamin consumption over the last century, and this might contribute to the observed postponing of aging manifestations. For example, the United States had started adding vitamin D to milk and some other dairy products since the 1930s because of the high prevalence of rickets and osteomalacia in northern climates at that time. We know now that vitamin D supplementation, along with calcium in milk, also reduces the risk of bone fractures in elderly women through amelioration of osteoporosis.

Another possible contributing factor to remarkable postponing of aging  may be a historical decline in disease load in early life. Facts are accumulating that many diseases and disabilities of older age have their roots in previous exposures to infection agents in early life. For example, chronic inflammation, which is common for many infectious diseases, is also related to later onsets of arthritis, atherosclerosis, diabetes, Alzheimer's disease and cancer.  Perhaps with improved sanitation, antibiotics, improved immune response through better nutrition and vaccination, the late-life debilitating effects of early-life infections were partially ameliorated.

In other words, many people expected that a cure for aging may come in the form of a magic pill (anti-aging drug). Instead, we largely overlooked the real and continuing progress in aging retardation, because it was so unanticipated and gradual (too slow for human perception).

For how long this historical trend of aging amelioration will continue? How far will it go?  Can this beneficial process be accelerated? These are good questions to study,  in addition to traditional search for anti-aging drugs.

My personal view is that future generations may be puzzled why we have overlooked some simple and readily available interventions, while  spending so much efforts on expensive and complex projects with dead ends.  This is like making the entire DNA sequence for scurvy patients instead of simply giving them a lemon...

Of course, aging is not that simple as scurvy is, and the most likely scenario for the future is a set of partial successes instead of one breakthrough.   We need to understand the current trends of historical amelioration of aging and to try to accelerate it.

Perhaps we need to pay more attention to latent infections in early life, prevention of pro-inflammatory conditions and to change radically the whole culture of human nutrition. For example, an encouraging accomplishments in smoking prevention in USA give some hope that perhaps similar efforts could be applied to control the obesity epidemic in this country. Food, which is high in vitamins, important minerals and other micronutrients, high in fiber content, while low in calories and animal fat may have a profound effect on further postponement of age-related degenerative diseases in later life.

To summarize, we can now speak about significant plasticity of aging as opposed to the previous concept of aging immutability. By acknowledging the aging plasticity, I do not wish to undermine the importance of future possible pharmacological interventions into the aging process and other potentially promising approaches including the cell therapy. On the contrary, these new experimental approaches may have a bright future, because even a much simpler approaches do work!
 

Question 6:
What is the current state of aging research?
How could we improve on ongoing research efforts to understand and intervene in human aging?

The current state of aging research can be described as a paradoxical one. On the one hand, almost every month we hear in the mass media about new exciting discoveries in aging studies. This creates an impression that aging studies are flourishing now.

What we do not hear in the news is how many interesting research opportunities are lost because of insufficient funding and how desperate are the scientists in their attempts to get research funding for aging studies.  Currently only 10-20% of research projects on aging are funded, so most of the promising research projects do not have even a chance to be started.

Much more generous funding of aging research is a key issue now, if we really wish to improve on ongoing research efforts to understand and intervene in human aging.

Consider for example our research team. Currently we have to spend more than a half of our professional time on paperwork just to get a research funding -- submission of the research proposals, their revision in response to review comments, re-submission of the revised proposals, and all this futile circle is repeated all over again and again !  What a wastage of precious professional time, which could be used much more productively for research work itself !  Our contacts with other colleagues confirm that our situation is not unique, so the wastage of professional time and effort on paperwork (projects writings, revisions and resubmitting) is really alarming.

By now we have three promising research projects on aging and longevity studies, which belong to the "high risk - high gain" category, and therefore have no chances to be funded in a regular way. We would be delighted to pass these projects for consideration of private philanthropists like Bill Gates or George Soros, if they ever choose to support aging studies. Also with the support of private foundations like for example the MacArthur Foundation, so many interesting projects on aging could be accomplished!

A radical improvement of the aging research funding is urgently needed, if we really wish to use the creative potential of researchers in its full capacity, instead of wasting it on a paperwork.
 

Question 7:
What are the most promising avenues of research and why?

Well, the answer to this question depends on the scientific goals you have in mind.

If we are really interested in extension of healthy lifespan in humans, not just in fruit flies, then perhaps we need to pay more attention to human studies.

Next, if we wish to study humans and their lifespan,  then we have to overcome two methodological obstacles. First, the opportunities for experiments with humans are limited.  Second, the studies on human lifespan may take too long time to wait.

 Both problems could be resolved through epidemiological and biodemographic studies of human longevity, when we analyze the experiments, which Mother Nature  has already performed with humans.  In other words the quantitative analysis of retrospective data on human longevity, including genealogical data, seems to be an extremely promising approach. This kind of studies may provide us with new important knowledge in a very short period of time.

These are not just words -- we have already developed a detailed research project for particularly promising avenues of research and even published it in this journal as an article "Epidemiology of human longevity: The search for appropriate methodology."  (JAAM, 2001, 4(1): 13-30). This project could provide us with a decisive knowledge on the mechanisms of human longevity just in 5 years.

Guess, what is the major obstacle in starting the work?  Yes, the lack of research funding...

How do we know that these avenues of research are really promising?  Well, we already made some amazing preliminary findings. For example, we found a very unusual pattern of  human lifespan inheritance.  Traditionally it was assumed that familial transmission of human lifespan from parents to children should follow a linear relationship, which is common to all other quantitative traits. In other words, for each additional year of  parental lifespan, the children were expected to have some fixed gain in their average lifespan too. Contrary to these conventional expectations, we discovered a very different, threshold pattern of lifespan inheritance -- there is no lifespan heritability if parental lifespan is below a threshold age of 75-85 years, and a very strong  heritability of human lifespan if parents live longer lives. These amazing preliminary findings are published as an article "When does human longevity start?: Demarcation of the boundaries for human longevity" in this journal (JAAM, 2001, 4(2): 115-124).

We also found that such an early circumstance of human life as the month of birth may have a profound effect 30 years later on the chances of human survival, which is also quite remarkable. This finding indicates that there may be critical periods early in human development particularly sensitive to seasonal  variation in living conditions in the past (e.g., seasonal vitamin deficiencies or seasonal exposure to pathogens, etc.). We published an article "Season of Birth and Human Longevity" in this journal (JAAM, 1999, 2(4): 365-366) on this exciting topic and recently reconfirmed our initial findings on larger datasets.

Another promising avenue of research is related to our finding that paternal age at person's conception may be an important predictor of person's lifespan. This finding suggests that the mutation load in paternal sperm cells may play a significant role in determining the length of human life.

Thus, there are so many exciting and promising  avenues for future research and the only problem is get a sufficient funding to accomplish them !
 

Question 8:
What are the most significant obstacles to anti-aging medicine?
How can they best be overcome?

The most important obstacle to anti-aging medicine now is a public confusion on the exact meaning and scientific credibility of anti-aging medicine. This confusion is reflected even in the title of the recent scientific article "Is There an Antiaging Medicine?" published by the Journal of Gerontology (2002, volume 57A, number 9, pp. B333-B338).

The term "anti-aging medicine" is currently used by three disparate groups of people in three completely different ways, which is the cause of a confusion.

First, there is a large group of scientists who publish their research findings in the Journal of Anti-Aging Medicine and other related peer-reviewed scientific journals. For them the anti-aging medicine is the ultimate goal of their research work (the medicine of the future)  aimed to control the aging process, postpone, delay, prevent and even to reverse the deleterious effects of aging. By now, over a hundred of important research articles has been published in the Journal of Anti-Aging Medicine, and these articles are now actively cited and used by the international scientific community.

If you make a search of the scientific literature for the term "anti-aging" you will find that this term is routinely used now in scientific literature (like the terms "anti-oxidant" or "antibiotic", for example), including the texts of scientific articles, their abstracts, key words selected by the authors, and even the titles of the scientific articles. I have recently performed such an analysis of the scientific literature and published these findings in the form of an article with self-explanatory title: "Scientific Legitimacy of the Term "Anti-Aging."  (Journal of Anti-Aging Medicine, 2002, 5(2): 239-240.). This article contains the list of legitimate anti-aging studies published in reputable journals by established researchers, which have the term "anti-aging" even in the title of these publications.

The second group of people, which  use  the term "anti-aging medicine"  is a group of medical practitioners. They are confronted with real and often urgent health needs of their aged patients.

For these physicians the anti-aging medicine is their everyday practice,  often by trial and error, aimed to alleviate, postpone, and hopefully even to prevent or reverse some detrimental manifestations of aging.

This is a rather diverse group. Some of their activities are in fact very useful, such as early detection and treatment of conditions , contributing to accelerated progress of age-related degenerative diseases. For example early detection and treatment of diabetes, hypertension, hypercholesterolemia, latent chronic infections,  chronic inflammation, obesity, vitamin and micronutrient deficiencies may postpone the onset of many detrimental manifestations of aging.

However, because of commercialization of the anti-aging industry, the advertisement hype and spam are not uncommon, and in some cases there is even a distinct smell of quackery and fraud. Unfortunately these marginal "anti-aging" groups are particularly noisy in excessive advertisements, thereby discrediting the very notion of anti-aging medicine.

Finally, there is a third group of people who believe that anti-aging interventions are neither possible nor desirable. They consider anti-aging medicine as an attempt of  "tampering with aging," which is both immoral and futile in their opinion. For them, "if it's "anti-aging" it's quackery by definition" (Science, 2002, 295, page 1033). They select the most ridiculous
and marginal cases of "anti-aging" quackery and expose them to the public, as if these cases are representative to anti-aging studies and the anti-aging medicine.

How these obstacles to anti-aging medicine could be best to overcome ?
Well, we need to spread a word in any place possible in order to educate the public and even some researchers on the existence of legitimate anti-aging science with its legitimate goal of developing the foundations for the future anti-aging medicine.

This educational work is already in progress. For example, recently the journal "Science" has published our consensus letter  "Antiaging technology and pseudoscience", signed by Dr. Michael Fossel, the Editor-in-Chief for the Journal of  Anti-Aging Medicine and by some other Editorial Board members of this journal, including myself. This publication did receive significant attention and initiated an interesting discussion published in Science online <http://www.sciencemag.org/cgi/eletters/296/5568/656a>
In this letter we did clearly spelled out the difference between the scientific, peer-reviewed Journal of Anti-Aging Medicine, and the popular magazines, serving for advertisements in anti-aging industry.

Still, a lot more need to be done to get more support and recognition for anti-aging medicine as a legitimate goal of scientific research. To address this issue, a year ago we have established a scientific and educational website entitled "Unraveling the Secrets of Human Longevity" <http://longevity-science.org/>. This information resource contains over a hundred of scientific documents supporting the ideas of anti-aging studies, and it has received about 23,000 visitors so far.

 I would urge other researchers to join our efforts and to contribute into further development of anti-aging medicine by spreading a word of support for it!
 

Question 9:
What advice would you give those starting their careers in this field?

First, I would like to welcome new researchers and congratulate them for the choice they have made.

Aging and longevity studies are so obviously important, that they will provide a sense of purpose to your life and inspiration for further research.

My advice could be summarized in a following way:

1.  Keep a sight of a big picture and a broad encyclopedic vision of the problem.
 In aging studies there is always a risk to be overwhelmed and distracted by details. There is also a temptation to be driven by new fancy techniques, so that the initial goals of research could be forgotten. Finally you may find yourself in a situation  like trying to read a newspaper through the electronic microscope. For example, there is a great interest now to the studies on differential gene expression during aging. However, aging may be also related to a simple decrease in cell numbers over time (loss of redundancy), and you can overlook this important possibility with too detailed fancy techniques.

2. Be persistent in your research efforts and be prepared to occasional failures.
Scientific research is always at risk of failure, because it is an exploration of unknown areas, often by trial and error. Therefore,  consider a failure not as an indicator of your research performance, but rather as a signal for choosing the alternative research tactics. Think how important are aging studies and this will protect you from too long periods of frustration, when your scientific project fails. If you have a sense of importance of your research work, this will give you a strength to start it again.
Be also prepared to the failure of funding of your research proposals. Here again, be responsive to criticism and change the tactics, but be persistent in strategic matters.

3. Use the data-driven approach, instead of following a doctrine.
Theories of aging are very important for organizing the accumulated facts into a comprehensive body of knowledge and for planning further research. Yet too often the researchers are becoming hostages of their own theories, when they try to "adapt" the facts to their concepts. I would advise not to treat the aging theories literally as "theories" to follow, but rather as a set of ideas that themselves require further elaboration and validation. Keep an open mind and a critical vision. For any statement, claim or reported finding try to seek for alternative opinion and listen their arguments carefully. Make final conclusions yourself, based on substance of the matter (facts), rather than apparent credibility of the sources. Famed authors and their publications in prestigious scientific journals at glossy paper may still be wrong. Be aware of conflicts of interests (follow the money that may produce deceptive claims). In difficult situations rely on your common sense and choose those outcomes where you can keep your peace of mind.
 

Question 10:
Do you have any other observations, insights, or suggestions regarding the field of aging and anti-aging medicine?

Yes, I believe that it is extremely important for researchers to understand that the prospects for future life extension revolution depend on their own behavior by the mechanism of self-fulfilling prophecy.

For example, if we convince ourselves and the public that nothing could be done and/or should be done with aging ("tampering with aging"), the outcome is clear.

On the other hand, the commitment of this nation already made possible several fantastic projects in the past (like the flight to the Moon), so why should we consider this generation less capable to great achievements?

The main challenge for accomplishing the life extension revolution is the mobilization of the nation and public support for relevant research projects. From this perspective, the recent attempts to discredit anti-aging research efforts and to present them as a kind of scientific porn should be taken very seriously and, in my opinion, these attempts should not to be endorsed. Moreover, it would be very useful to establish a prestigious Anti-Aging Science Award in order to stimulate legitimate anti-aging scientific studies and public support for them.

Anti-aging research project will require large-scale and long-term intervention trials with human subjects, which is very expensive and will require careful governmental supervision to minimize research health risks. In other words, this ambitious anti-aging project requires mobilization of the nation and a public support for it -- just like it was with the flight to the Moon, for example. You just can not move forward alone, by collecting gasoline in your apartment for future flight to the Moon. The same is true with the anti-aging project.

The anti-aging project may even require joint efforts of many nations, and this ambitious collaborative project may help to bring many nations together. The mankind already has some previous positive experience of scientific collaboration (exploration of space, for example), and the anti-aging project may help to strengthen further the cooperation between nations.

It is important therefore to put the issue of aging prevention in the center of public debates now, so that by the next presidential elections it become the key political issue. We should not lose any opportunity to express publicly our opinion on anti-aging studies and the supporting arguments we may have. We will have the future that we deserve.


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