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

1

Becoming Immortal

Combining Cloning and Stem-Cell Therapy

• Shostak, S., Albany SUNY Press 2002.

2

Toward a Theory of Immortality
The Reallocation of Stem Cells

• Shostak, S., 2004.

3
Is Homo sapiens evolving before our eyes, and can
we analyze this evolution as it happens?

1. The already known

Increasing lifespan Decreasing fecundity

1. The chronic disease model

simulating change
The accordion uniform expansion The bagpipe
expansion at one stage

1. 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?

1. 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
or where you look for it!
5
no data available
Foster, George M., Old age in Tzintzuntzan,
Mexico, pp. 115137. 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?

1. 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
Pregnancy Rates 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,
31246771 1996.
12
Is Homo sapiens evolving before our eyes, and can
we analyze this evolution as it happens?

1. The already known

Increasing lifespan Decreasing fecundity

1. The chronic disease model

Is there a biological explanation?
13
Life as a Chronic Disease
stage
death
age
14
embryo

Vembryo(x)
?embryo(x)
fetus
Vfetus(x)
?fetus(x)
neonate
death
?neonate(x)
Stages
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
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16
Is Homo sapiens evolving before our eyes, and can
we analyze this evolution as it happens?

1. The already known

Increasing lifespan Decreasing fecundity

1. The chronic disease model

simulating change
The chronic disease model
17
Is Homo sapiens evolving before our eyes, and can
we analyze this evolution as it happens?

1. The already known

Increasing lifespan Decreasing fecundity

1. The chronic disease model

simulating change
Each stage of a lifetime expands and contracts.
18
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
19
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Is Homo sapiens evolving before our eyes, and can
we analyze this evolution as it happens?

1. The already known

Increasing lifespan Decreasing fecundity

1. 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?
21
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
22
Chiang, Chin Long, The Life Table and Its
Applications. Malabar, FL Robert E. Krieger
1984.
23
Chiang, Chin Long, The Life Table and Its
Applications. Malabar, FL Robert E. Krieger
1984.
24
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
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26
pg.
27
pg.
28
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.
29
Is Homo sapiens evolving before our eyes, and can
we analyze this evolution as it happens?

1. The already known

Increasing lifespan Decreasing fecundity
Increasing lifespan Decreasing fecundity

1. The chronic disease model

simulating change
The accordion uniform expansion The bagpipe
expansion at one stage
The accordion The bagpipe

1. Hypotheses for testing

Is there a biological explanation?
30

1. 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

31
How might a lifetime be juvenilized and a
lifespan lengthened?
32
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

33
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
34
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 to stress by
regenerating damaged tissue and renewing their
population.
35
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.
36
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/MainPage
37
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?

38
Is Homo sapiens evolving before our eyes, and can
we analyze this evolution as it happens?

1. The already known

Increasing lifespan Decreasing fecundity
Changes in lifespan and fecundity are due to
changes in the allocation of stem-cells.

1. Hypotheses for testing

39

Toward a Theory of Immortality
The Reallocation of Stem Cells

• Shostak, S., 2004.