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*:Shostak, S., Albany: SUNY Press; 2002.

Becoming Immortal. *. *:Shostak, S., Albany: SUNY Press; 2002. Combining Cloning and Stem-Cell Therapy. Toward a Theory of Immortality. Shostak, S., 2004. The Reallocation of Stem Cells. Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens?.

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*:Shostak, S., Albany: SUNY Press; 2002.

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  1. Becoming Immortal * *:Shostak, S., Albany: SUNY Press; 2002. Combining Cloning and Stem-Cell Therapy

  2. Toward a Theory of Immortality Shostak, S., 2004. The Reallocation of Stem Cells

  3. Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity The chronic disease model simulating change The accordion: uniform expansion The bagpipe: expansion at one stage Hypotheses for testing and a mechanism for theorizing Is there a biological explanation? Neoteny Changes in lifespan and fecundity are due to changes in the allocation of stem-cells.

  4. Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known No matter how you measure it: Increasing lifespan the absolute life span limit, maximum life-span potential, a practical life span limit, an age at which the force of mortality is close to unity, an age up to which a certain proportion of the population survives, or a theoretically maximal age orwhere you look for it!

  5. Tzintzuntzan Deaths: 1940–1949 and 1969–1978 Tzintzuntzan population: 1940–1949 and 1969–1978 totaldeaths population years years no data available Foster, George M., Old age in Tzintzuntzan, Mexico, pp. 115–137. inAging: Biology and Behavior, James L. McGaugh and Sara B. Kiesler, eds., New York: Academic Press; 1981.

  6. pg.

  7. Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity

  8. birth rates per 1000 population year Intrinsic fertility rates: rates that would eventually prevail if population were to experience the age-specific birth rates for a given year over a long period of time. Data from Table 1-6, pg. 7. National Center for Health Statistics. Vital Statistics of the United States, 1993, Vol 1, Natality. Hyattsville, Maryland. 1999.

  9. Birth Rates by Age of Mother in U.S. from 1960 to 1993 5-year age groups of mothers Live births per 1,000 women in specified groups years National Center for Health Statistics. Vital Statistics of the United States, 1993, vol 1, natality. Hyattsville, Maryland. 1999.

  10. PregnancyRates by Age of Mother in U.S. from 1980 to 1999 Revised for consistency with 2000 census.

  11. Irvine, S., et al., Evidence of deteriorating semen quality in the United Kingdom. BMJ, 312:467–71; 1996.

  12. Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity The chronic disease model Is there a biological explanation?

  13. old adult young adult senescent adolescent juvenile neonate Life table begins fetus embryo Life as a Chronic Disease stage death age

  14. Life tables begin here embryo Vembryo(x) embryo(x) fetus Vfetus(x) fetus(x) neonate death Stages neonate(x) Vneonate(x) juvenile(x) juvenile Vjuvenile(x) adolescent(x) adolescent Vadolescent(x) young adult(x) young adult old adult(x) Vyoung adult(x) senescent(x) old adult Vold adult(x) senescent

  15. uniform expansion The accordion expansion at one stage The bagpipe Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity The chronic disease model The chronic disease model simulating change

  16. uniform expansion The accordion Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity The chronic disease model simulating change Each stage of a lifetime expands and contracts.

  17. The Accordion Model expanded old adult expanded young adult old adult young adult expanded senescence senescent expanded adolescent stage adolescent death death death expanded juvenile death death juvenile expanded neonate neonate expanded fetus fetus expanded embryo embryo age

  18. Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity The chronic disease model simulating change uniform expansion The accordion The bagpipe expansion at one stage Which stage has the greatest potential for expanding longevity? has the lowest death rate?

  19. The actually observed graph of mortality against age. The dependence of the force of mortality on age for Swedish women in 1980. Source of the data: Befolkningsförändingar, 1980. Gavrilov, Leonid A. and Natalia S. Gavrilova, The Biology of Life San: A Quantitative Approach. Revised and updated English Edition; 1991, pg. 164. Used with permission

  20. Chiang, Chin Long, The Life Table and Its Applications. Malabar, FL: Robert E. Krieger; 1984.

  21. Chiang, Chin Long, The Life Table and Its Applications. Malabar, FL: Robert E. Krieger; 1984.

  22. The Bagpipe Model extension of the juvenile stage to later stages of the lifetime old adult young adult senescent stage adolescent juvenile death neonate fetus age embryo

  23. pg.

  24. pg.

  25. Juvenilization: the expansion of youthful anatomy and physiology to the later stages of a lifetime, i.e., ‘forever young.’ Paedogenesis:“sexual maturity occurs before the organism reaches the full size or relative proportions (shape) of closely related species.”* • Progenesis:“precocious sexual maturation with other somatic tissues at their usual state of immature development for that age • Neoteny or fetalization:“sexual maturation at the usual age, but with retarded development of the other somatic tissues.”* *: Finch, C.E., Longevity, Senescence, and the Genome. Chicago: The University of Chicago Press; 1990, pg. 629.

  26. neoteny the ^ Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity Increasing lifespan Decreasing fecundity The chronic disease model simulating change The accordion:uniform expansion The bagpipe:expansion at one stage The accordion The bagpipe Hypotheses for testing Is there a biological explanation?

  27. Hypotheses for testing • slope of adult mortality curve should be dropping in the direction of the juvenile mortality curve • morphological features of the juvenile should be preserved and extended. • juvenile state of growth and modulation of bone should not be brought to a halt • thymic involution, with all its consequences for the immune response should be retarded, delayed, or even suspended

  28. Genetics: (polygenic) Mendelian control Environment:Directly inducible Epigenetics:NonMendelian heritability How might a lifetime be juvenilized and a lifespan lengthened?

  29. Genetics: (polygenic) Mendelian control • Juvenile phase spread by acquisition and accumulation of pro-juvenile mutations and elimination or dilution of anti-juvenile and aging Mendelian genes. • Pedigrees and familial correlations at the age of death • Twin studies: Lifespan heritability • Maximum longevity possible or lifespan limits: the compensation effect of mortality • Experimental genetics of so-called model organisms

  30. Genetics: (polygenic) Mendelian control • Juvenile phase spread by acquisition and accumulation of pro-juvenile mutations and elimination or dilution of anti-juvenile and aging Mendelian genes. Environment:Directly inducible Juvenile phase enhanced by external conditions such as hypothermia, nutritional deprivation and stress (not adversity). Pressures and tensions on metabolic regulation, reproductive control, the inhibition of cellular proliferation, and the promotion of programmed cell death. “the transcriptional equivalent of the fountain of youth”

  31. The stem cell “fountain of youth” or “antithesis of aging,” “redundant elements that function as backups in the event of failure” Adult stem cells continuously restore vigor to tissues and organs by replacing effete cells while, at the same time, renewing the adult stem-cell population. Reserve stem cells respond tostressby regenerating damaged tissue and renewing their population.

  32. Genetics: (polygenic) Mendelian control Environment:Directly inducible Lamarckian ^ Epigenetics:NonMendelian heritability • Juvenile phase spread by acquisition and accumulation of pro-juvenile mutations and elimination or dilution of anti-juvenile and aging Mendelian genes. Juvenile phase enhanced by hypothermia, nutritional deprivation and stress (not adversity). • Juvenile phase expanded by changes that increase robustness and diminution of frailty but are not inherited according to the rubric of Mendelian genetics.

  33. Epigenetics: * The study of the processes involved in the unfolding development of an organism. This includes phenomena such as X chromosome inactivation in mammalian females, and gene silencing within an organism. • DNA methylation • Delayed DNA methylation • DNA de-methylation * The study of heritable changes in gene function that occur without a change in the sequence of nuclear DNA. This includes the study of how environmental factors affecting a parent can result in changes in the way genes are expressed in the offspring. * Wikipedia, The Free Encyclopedia: http://en2.wikipedia.org/wiki/Main+Page

  34. In sum: • Do adult and reserve stem cells share a common origin with embryonic germ cells in the embryonic stem cell population? • Are epigenetic influences nudging embryonic stem-cells away from the germ line? • Are longevity and fecundity functions of stem cell allocation in adults?

  35. neoteny the ^ Is there a biological explanation? Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? The already known Increasing lifespan Decreasing fecundity Changes in lifespan and fecundity are due to changes in the allocation of stem-cells. Hypotheses for testing

  36. Toward a Theory of Immortality Shostak, S., 2004. The Reallocation of Stem Cells

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