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Interview with Leonid A. Gavrilov, Ph.D. - page 2 / 4





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findings could lead to the identification and confirmation of therapeutic and preventive strategies and health policies to combat aging. To make this a reality we have developed a research project called the Biodemography of Exceptional Longevity, which was recently awarded a grant from the U.S. National Institute on Aging (NIA). Some preliminary findings have already published.29–31 We continually update information about the progress of this research project on our scientific website entitled Unraveling the Secrets of Human Longevity’ (http:==longevity-science.org=). We also welcome comments and public discussion at our blog, Longevity Science (http:==longevity-science.blogspot.com=).

Second of value is traditional demography, which provi- des tools for making demographic projections for different scenarios of life extension. This is important because a common objection against starting a large-scale biomedi- cal war on aging is the fear of catastrophic population consequences—that is, overpopulation. This fear is only ex- acerbated by the fact that no detailed demographic projec- tions for a radical life extension scenario have yet been published. What would happen to population numbers if aging-related deaths were significantly postponed or even eliminated? Is it possible to have a sustainable population dynamic in a future, hypothetical nonaging society? These are important questions that could be answered through traditional demographic studies.

Recently, we have completed a new study that explores different demographic scenarios and population projections, with the goal of clarifying the demographic consequences of a successful biomedical war on aging. The results of this study, which was supported by the Methuselah Foundation and the SENS Foundation, were presented at the SENS4 conference in Cambridge, United Kingdom, this past Sep- tember, and will be published shortly.32 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 overpop- ulation. Amazingly, on our return trip to the United States from SENS4, the passport control officer asked us exactly this same question about overpopulation during the interview about the purpose of our international travel! This example indicates how deeply the fear of overpopulation penetrates the fabric of modern society, and hence the importance of demographic studies on this topic.

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?

It is true that predicting longevity trends remains a chal- lenging task. Moreover, our own analyses of Russian mor- tality data convinced us that a significant long-term drop in life expectancy can occur even in developed countries with- out any major wars.33–35 Thus, there is a significant uncer- tainty not only concerning the pace of further longevity increase, but even the direction of future changes in life ex- pectancy. 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 shift from traditional extrapolations of current mor- tality trends to deeper analyses of expert judgments on fu-


ture mortality risks as well as emerging opportunities in the biomedical sciences.

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 incor- porate significant in-built self-repair machinery. To what extent do you feel that this difference diminishes the appli- cability of reliability theory to living organisms?

Thank you for your kind use of the term ‘‘spearheading.’’ Yes, we first started to apply reliability theory to the problem of biological aging more than 30 years ago, as early as 1978,36,37 and since that time the reliability theory of aging and longevity has become well known in the scientific lit- erature.38–44 In answer to your question on the applicability of reliability theory to living organisms, it is useful to con- sider separately two different topics: (1) the applicability of reliability theory as a general concept; and (2) the applica- bility of our particular mathematical models that are based on reliability theory.

In 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 ki- netics for a system of given architecture (reliability struc- ture) and given reliability of its components. Although historically it was initially applied to describe the behavior of man-made machines, nothing in this general mathe- matical theory prevents us from taking into account the built-in self-repair machinery. Therefore, there is nothing fundamentally wrong with applying reliability theory to living organisms, or, more generally, applying mathemat- ics to living organisms.

With regard to the second topic, it was our initial intent to find the simplest explanation for the major facts about aging and mortality, including the very origin of aging, the Gom- pertz law of mortality, the compensation law of mortality, and late-life mortality deceleration. We were interested in understanding the first principles and fundamental expla- nations of aging before trying to create a comprehensive model that would take into account all the complexities of living organisms. Therefore, in our models we have focused on the accumulation of unrepaired damage as the final out- come of the damage versus repair process, which leads to an age-related decrease in systems redundancy (e.g., a decrease in numbers of functional cells). When these intentionally simplified models, based on a minimum number of as- sumptions, gave us some general understanding of the na- ture of the aging process and mortality laws, it opened the way to build upon this knowledge to create a more detailed and complex model of aging. This challenge is open to anyone with the time to pursue it.

Another interesting feature of biological systems is that they are formed in evolution during a severe struggle for survival—a biological arms race with numerous infectious agents and predators. As a result, these systems have many potentially harmful defense mechanisms that may be useful for short-term survival in hostile, wild environments, but are not conducive for longevity in a protected environment. An example of this would be the inflammatory response. So the analogy between living organisms and man-made machines is most appropriate for man-made military machines that are

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