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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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slide1
Becoming Immortal

*

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

Combining Cloning and Stem-Cell Therapy

slide2
Toward a Theory of Immortality

Shostak, S., 2004.

The Reallocation of Stem Cells

slide3
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.

slide4
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!

slide5
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.

slide7
Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens?

The already known

Increasing lifespan

Decreasing fecundity

slide8
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.

slide9
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.

slide10
PregnancyRates by Age of Mother in U.S. from 1980 to 1999

Revised for consistency with 2000 census.

slide11
Irvine, S., et al., Evidence of deteriorating semen quality in the United Kingdom. BMJ, 312:467–71; 1996.
slide12
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?

slide13
old adult

young adult

senescent

adolescent

juvenile

neonate

Life table begins

fetus

embryo

Life as a Chronic Disease

stage

death

age

slide14
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

slide16
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

slide17
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.

slide18
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

slide20
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?

slide21
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

slide22
Chiang, Chin Long, The Life Table and Its Applications. Malabar, FL: Robert E. Krieger; 1984.
slide23
Chiang, Chin Long, The Life Table and Its Applications. Malabar, FL: Robert E. Krieger; 1984.
slide24
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

slide28
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.

slide29
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?

slide30
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
slide31
Genetics: (polygenic) Mendelian control

Environment:Directly inducible

Epigenetics:NonMendelian heritability

How might a lifetime be juvenilized and a lifespan lengthened?

slide32
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
slide33
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”

slide34
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.

slide35
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.
slide36
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

slide37
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?
slide38
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

slide39
Toward a Theory of Immortality

Shostak, S., 2004.

The Reallocation of Stem Cells

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