8 replies to this topic

[gavrilov]

Greetings,

This is just to alert you about new interview on aging and longevity studies, which is published this week by the 'Rejuvenation Research' journal:

Rejuvenation Research, 2009, 12(5): 371-374.
http://www.lieberton...9/rej.2009.0979
and:
http://health-studie...iew-RR-2009.pdf

Any comments and suggestions are welcome! Please feel free to post your comments and suggestions here:
http://tinyurl.com/ydpnvhe


Thank you, and Happy Thanksgiving!


-- Leonid


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-- Leonid Gavrilov, Ph.D. , GSA Fellow
Center on Aging, NORC/University of Chicago
Website: http://longevity-science.org/
Blog: http://longevity-science.blogspot.com/
Our books: http://longevity-sci....org/Books.html

[gavrilov]

Greetings,

Also, here are some excerpts from this published interview (original non-edited text):

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Question:
1. How, in general, can demographers contribute to the effort to develop medical treatments to combat aging?


Answer:

There are several ways how human population studies could be very useful for efforts to extend healthy life span.

First, there is an area of biodemography - a science, which integrates biological knowledge with demographic approaches in attempt to understand the dynamics of vital events in human populations, including mortality and longevity [1-4]. Looking back at the history of science we can see that such important health findings as the discovery of long-term harmful effects of smoking, hypertension, high cholesterol levels and hyperglycemia all came from statistical (epidemiological) studies on human populations. These significant findings from population studies served as a guide and justification for subsequent development of specific medical treatments and health policies already saving many human lives now.

Looking forward at the future of biodemographic studies, we anticipate 'unraveling the secrets of human longevity' -- the discovery of determinants for exceptional human survival, which allow some individuals to delay dramatically many diseases of aging, and to live a remarkably healthy long life (sometimes beyond 100 years). When we find out why some people are so resilient to aging, these findings could serve as a guide and justification for development of new medical treatments and health policies to combat aging. To make this happen we developed a new research project 'Biodemography of Exceptional Longevity', which was recently awarded a grant from the U.S. National Institute on Aging, NIA. Information about the progress of this research project is continually updated at our scientific website 'Unraveling the secrets of human longevity' ( http://longevity-science.org/ ), and it is opened for comments and public discussion at our blog 'Longevity Science' ( http://longevity-science.blogspot.com/ ). Some preliminary findings on this topic are already published [5-7].

Second, there is an area of traditional demography, which has tools to make demographic projections for different scenarios of life extension. This is an important issue, because a common objection against starting a large-scale biomedical war on aging is the fear of catastrophic population consequences (overpopulation). This fear is only exacerbated by the fact that no detailed demographic projections for radical life extension scenario were published so far. What would happen with population numbers if aging-related deaths are significantly postponed or even eliminated? Is it possible to have a sustainable population dynamics in a future hypothetical non-aging society? These are important questions, which could be answered through traditional demographic studies.

Recently we made a new study, which explores different demographic scenarios and population projections, in order to clarify what could be the demographic consequences of a successful biomedical war on aging. The results of this study supported by the Methuselah and SENS foundations were presented at the SENS4 conference in Cambridge, UK, this September, and are expected to be published [8]. In brief, we found that defeating aging, the joy of parenting and sustainable population size are not mutually exclusive. This is an important point, because it can change the current public perception that life-extension necessarily leads to overpopulation. Amazingly, when we were returning back to the USA from the SENS4 conference in England, the passport control officer asked us exactly the same question about overpopulation during the interview about the purpose of our international travel! This example indicates how deep is the penetration of overpopulation scare in the fabrics of modern society, and hence how important are the demographic studies on this topic.

References

1. Curtsinger JW, Gavrilova NS, Gavrilov LA. Biodemography of Aging and Age-Specific Mortality in Drosophila melanogaster. In: Masoro E.J. & Austad S.N.. (eds.): Handbook of the Biology of Aging, Sixth Edition. Academic Press. San Diego, CA, USA, 2006, 261-288.

2. Gavrilov L.A., Gavrilova N.S., Olshansky S.J., Carnes B.A. Genealogical data and biodemography of human longevity. Social Biology, 2002, 49(3-4): 160-173.

3. Gavrilov, L.A., Gavrilova, N.S. Biodemographic study of familial determinants of human longevity. Population: An English Selection, 2001, 13(1): 197-222.

4. Gavrilova, N.S., Gavrilov, L.A. Data resources for biodemographic studies on familial clustering of human longevity. Demographic Research [Online], 1999, vol.1(4): 1-48. Available: http://www.demograph...Volumes/Vol1/4/

5. Gavrilova N.S., Gavrilov L.A. Can exceptional longevity be predicted? Contingencies [Journal of the American Academy of Actuaries], 2008, July/August issue, pp. 82-88.

6. Gavrilova N.S., Gavrilov L.A. Physical and Socioeconomic Characteristics at Young Age as Predictors of Survival to 100: A Study of a New Historical Data Resource (U.S. WWI Draft Cards). Living to 100 and Beyond: Survival at Advanced Ages [online monograph]. The Society of Actuaries, 2008, 23 pages.

7. Gavrilova N.S., Gavrilov L.A. Search for Predictors of Exceptional Human Longevity: Using Computerized Genealogies and Internet Resources for Human Longevity Studies. North American Actuarial Journal, 2007, 11(1): 49-67.

8. Gavrilov L.A., Gavrilova N.S. Demographic Consequences of Defeating Aging. [Meeting Abstract]. Rejuvenation Research, 2009, 12( Suppl. 1): 29-30.

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[gavrilov]

Greetings,

Here is Part 2 of excerpts from the published interview (original non-edited text):

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Question 2:

2. Predictions of future trends in longevity have always been notoriously incorrect. Is this because reliable indicators of future trends do not exist or because those indicators are not recognized as useful by those making the predictions?


Answer:

Yes, it is true that predicting longevity trends remains to be a challenging task. Moreover our own analyses of Russian mortality data convinced us that a significant long-term drop in life expectancy can occur even in developed countries without any major wars [1-3]. Thus, there is a significant uncertainty not only for the pace of further longevity increase, but even for the direction of future changes in life expectancy. This does not mean, in our opinion, that longevity predictions could not be improved further by finding more reliable indicators of future trends. Perhaps the emphasis should be shifted from traditional extrapolations of current mortality trends to a deeper analyses of expert judgements on future mortality risks as well as new emerging opportunities of biomedical sciences.


References

1. Gavrilova N.S., Semyonova V.G., Dubrovina E., Evdokushkina G.N., Ivanova A.E., Gavrilov L.A. Russian Mortality Crisis and the Quality of Vital Statistics. Population Research and Policy Review, 2008, 27: 551-574.

2. Gavrilova, N.S., Gavrilov, L.A., Semyonova, V.G., Evdokushkina, G.N., Ivanova, A.E. 2005. Patterns of violent crime in Russia. In: Pridemore, W.A. (ed.). Ruling Russia: Law, Crime, and Justice in a Changing Society. Boulder, CO: Rowman & Littlefield Publ., Inc, 117-145.

3. Gavrilova, N.S., Semyonova, V.G., Evdokushkina G.N., Gavrilov, L.A. The response of violent mortality to economic crisis in Russia. Population Research and Policy Review, 2000, 19: 397-419.

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[gavrilov]

Greetings,

Here is Part 3 of excerpts from the published interview (original non-edited text):

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Question 3:

3. You have spearheaded the application of reliability theory to the modeling of aging and mortality. Reliability theory is designed to describe the behavior of man-made machines, which differ from living organisms in that they do not incorporate significant in-built self-repair machinery. To what extent do you feel that this difference diminishes the applicability of reliability theory to living organisms?


Answer:

Thank you for your kind comment on our 'spearheading' . Yes, we first started to apply reliability theory to the problem of biological aging more than 30 years ago, as early as in 1978 [1, 2], and since that time the reliability theory of aging and longevity has become well known in scientific literature [3 - 9]. To answer your question on applicability of reliability theory to living organisms, it is useful to consider separately two different topics: (1) applicability of reliability theory as a general concept; and (2) applicability of our particular mathematical models based on reliability theory.

Discussing the first topic, it is important to note that reliability theory is a general theory about systems failure. It allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Although historically it was initially applied to describe the behavior of man-made machines, nothing in this general mathematical theory prevents us from taking into account the in-built self-repair machinery, if this is needed. Therefore, there are no fundamental problems with applicability of reliability theory to living organisms, as there are no problems in applicability of mathematics in general to living organisms.

Discussing the second topic, it was our initial intent to find the most simple explanation for the major facts about aging and mortality (the very origin of aging, the Gompertz law of mortality, the compensation law of mortality, and the late-life mortality deceleration). We were interested in understanding the first principles and fundamental explanations of aging, before trying to create a comprehensive model, which takes into account all the complexities of living organisms. Therefore, in our models we were focused on accumulation of un-repaired damage as the final outcome of the damage-vs-repair process, leading to age-related decrease in systems redundancy (e.g. decrease in numbers of functional cells).

Now, when these intentionally simplified models with minimum number of assumptions gave us some general understanding of the nature of aging process and mortality laws, the way is opened to build upon them a more detailed and complex model of aging. This work is opened to everyone who can find a protected time to do it.

Another interesting feature of biological systems is that they are formed in evolution during a severe struggle for survival, and biological arms race with numerous infections and predators. Therefore they have many potentially harmful defense mechanisms, which may be useful for short-term survival in hostile wild environment, but not conductive for longevity in a protected environment (like the inflammation response).

So the analogy between living organisms and man-made machines is more appropriate for a man-made military machines, overloaded by weaponry and ammunition at the expense of their durability. Such machines could last much longer in protected environment if many dangerous fighting devices are removed from them.

The same is true for living organisms -- loss of some functions through introduced mutations or other interventions often leads to increased species longevity in a protected environment. Sometimes this observation is interpreted as a proof that aging is a programmed process, while in fact it simply means that organisms were selected by Nature for survival in the wild hostile environment, rather than for longevity in protected laboratory conditions.


References

1. Gavrilov, L.A. A mathematical model of the aging of animals. Proc. Acad. Sci. USSR [Doklady Akademii Nauk SSSR], 1978, 238(2): 490-492. English translation by Plenum Publ Corp: pp.53-55. PMID 624242

2. Gavrilov, L.A., Gavrilova, N.S., Yaguzhinsky, L.S. The main regularities of animal aging and death viewed in terms of reliability theory. J. General Biology [Zhurnal Obschey Biologii], 1978, 39(5): 734-742. PMID 716614

3. Gavrilov LA, Gavrilova NS. Reliability Theory of Aging and Longevity. In: Masoro E.J. & Austad S.N.. (eds.): Handbook of the Biology of Aging, Sixth Edition. Academic Press. San Diego, CA, USA, 2006, 3-42. ISBN 0-12-088387-2

4. Gavrilov LA, Gavrilova NS. Models of Systems Failure in Aging. In: P Michael Conn (Editor): Handbook of Models for Human Aging, Burlington, MA : Elsevier Academic Press, 2006. 45-68. ISBN 0-12-369391-8.

5. Gavrilov LA, Gavrilova NS. Why We Fall Apart. Engineering's Reliability Theory Explains Human Aging. IEEE Spectrum, 2004, 41(9): 30-35.

6. Gavrilov LA, Gavrilova NS. The Reliability-Engineering Approach to the Problem of Biological Aging. Annals of the New York Academy of Sciences, 2004, 1019: 509-512. PMID 15247076

7. Gavrilov L.A., Gavrilova N.S. The quest for a general theory of aging and longevity. Science's SAGE KE (Science of Aging Knowledge Environment) for 16 July 2003; Vol. 2003, No. 28, 1-10. http://sageke.sciencemag.org , PMID 12867663

8. Gavrilov L.A., Gavrilova N.S. The reliability theory of aging and longevity. Journal of Theoretical Biology, 2001, 213(4): 527-545. PMID 11742523

9. Gavrilov L.A., Gavrilova N.S (1991), The Biology of Life Span: A Quantitative Approach. New York: Harwood Academic Publisher, ISBN 3-7186-4983-7

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[gavrilov]

Greetings,

Here is Part 4 of excerpts from the published interview (original non-edited text):

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Question 4:

4. Recently you developed novel software to describe the demographic consequences of therapies that genuinely reverse, rather than merely retard the advance of biological age (i.e., the life-long accumulation of the "damage" that causes age-related ill-health when it becomes sufficiently abundant). Were you surprised at the predictions that this scenario yielded?

Answer:

Yes, we were surprised by some of our own findings. For example, consider the 'worst' case scenario (for overpopulation) -- physical immortality (no deaths at all). What would happen with population numbers then? A common sense and intuition says that there should be a demographic catastrophe, if immortal people continue to reproduce. That is what we initially believed too.

However a deeper mathematical analysis leads to paradoxical results. If parents produce less than two children on average, so that each next generation is smaller by some common ratio (R < 1), then even if everybody is immortal, the final size of the population will not be infinite, but just 1/(1 - R) times larger than the initial population. For example, one-child practice (R = 0.5) will only double the total immortal population, because 1/(1 - 0.5) = 2. In other words, a population of immortal reproducing organisms can grow indefinitely in time, but not necessarily indefinitely in size, because asymptotic growth is possible [1].

The beauty of this finding is that it does not require any complex calculations and questionable assumptions, but follows directly from the calculus, and the property of infinite geometric series to converge when the absolute value of the common ratio R is less than one. So, the fears of overpopulation based on lay common sense and uneducated intuition are in fact grossly exaggerated. It was a great surprise to us that just a bit of clear thinking with simple mathematics can make such a difference in resolving a problem.


References

1. Gavrilov L.A., Gavrilova N.S. Demographic Consequences of Defeating Aging. [Meeting Abstract]. Rejuvenation Research, 2009, 12( Suppl. 1): 29-30.

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[gavrilov]

Greetings,

Here is Part 5 of excerpts from the published interview (original non-edited text):

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Question 5:

5. Demographic predictions are of immense importance in determining economic and social policy, in view of the impact of factors such as dependency ratio on the relative economic viability of different policies. Thus, it seems essential that policy-makers and other opinion-formers take demographers' work seriously. What can be done to encourage influential people to understand the importance of such predictions and to act on them?



Answer:

In order to increase the impact of demographic predictions on economic and social policy it is important to have very active and persistent strategic outreach program. In other words, we need to stimulate demographers to make more reader-friendly publications in high profile editions, to organize more joint conferences of demographers with policy-makers and other opinion-formers, and more public meetings and discussions of demographers with influential people. This strategic outreach program could become successful in the case of a strong support from foundations of wealthy visionaries, such as Peter Thiel, Bill Gates and Larry Ellison, for example.

Also it may be helpful to strengthen the demographic component in current anti-aging research programs, such as for example the 'Science Against Aging' program, which was developed recently by the International Foundation 'Science for Life Extension' [1].


References

1. 'Science Against Aging' program. 2009. International Foundation 'Science for Life Extension', Moscow, Russia, 125 pages
published online at: http://www.scienceag...6_2009_razv.pdf


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[AgeVivo]

We can only say bravo to all this great work: bravo!

[gavrilov]

We can only say bravo to all this great work: bravo!

Thank you for your kind comments!

Here is the last Part 6 of excerpts from the published interview (original non-edited text):

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Question 6:


6. What factors in the industrialized world, do you think most strongly influence the following: (a) the number of children women have; and (b) the average age at which women have their first child? How do you think these factors would be altered by the advent of therapies that combat aging, including menopause?


Answer:

We believe that the key variable most strongly influencing fertility in the industrialized world is the opportunity cost of having a child. This is the cost of childbearing in terms of time and resources, and, most important, the intensity of competition between this choice and other opportunities in life. For example, a demanding job could prevent some career oriented women from having a child before they established themselves. Risk of losing a partner could be another opportunity cost, particularly for unmarried partners, cohabitating without strong commitments. Desire to have a flexible life style (mostly at young ages), or concerns about health consequences of childbearing (particularly at older ages) represent some other examples of perceived opportunity costs for having a child.

With the advent of therapies that combat aging, including menopause, the pressure on women to have a child 'before it is too late' may decrease. However we have to make sure that with new therapies children born to older parents will be as healthy as those who are born to younger parents. Our own studies, as well as the abundant biomedical literature indicate that currently both the advanced paternal and maternal ages at person's birth have significant negative effects on person's health and longevity, therefore at this time it is better to avoid delayed parenting [1 - 4].


References

1. Gavrilova N.S., Gavrilov L.A. Search for Predictors of Exceptional Human Longevity: Using Computerized Genealogies and Internet Resources for Human Longevity Studies. North American Actuarial Journal, 2007, 11(1): 49-67.

2. Gavrilov LA, Gavrilova NS. Early-life programming of aging and longevity: The idea of high initial damage load (the HIDL hypothesis). Annals of the New York Academy of Sciences, 2004, 1019: 496-501.

3. Gavrilov, L.A., Gavrilova, N.S. Early-life factors modulating lifespan. In: Rattan, S.I.S. (Ed.).Modulating Aging and Longevity. Kluwer Academic Publishers, Dordrecht, The Netherlands, 2003, 27-50.

4. Gavrilov, L.A., Gavrilova, N.S. Human longevity and parental age at conception. In: J.-M.Robine et al. (eds.) Sex and Longevity: Sexuality, Gender, Reproduction, Parenthood, Berlin, Heidelberg: Springer-Verlag, 2000, 7-31.

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[gavrilov]

Greetings,

Russian translation of this interview is now available at:

http://www.scienceag...s/press_10.html

Hope it helps.

.