*:shostak, s., albany: suny press; 2002

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

*

Shostak, S., 2004.

Is Homo sapiens evolving before our eyes, and can we analyze this evolution as it happens? 1) The already known

Increasing lifespanDecreasing fecundity

2) The chronic disease modelThe accordion: uniform expansionThe bagpipe: expansion at one stage

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

Is there a biological explanation?

3) Hypotheses for testing and a mechanism for theorizing

Neoteny

simulating change

1) The already known

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

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

No matter how you measure it:

or where you look for it!

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.

Tzintzuntzan Deaths: 1940–1949 and 1969–1978

years

0

5

10

15

20

25

40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78

total deaths

tota

l death

s

years

Tzintzuntzan population: 1940–1949 and 1969–1978

0

500

1000

1500

2000

2500

3000

40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78

total population size

popu

lati

on

no data available

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.

year

0

5

10

15

20

25

30

60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92

Intrinsic fertility rates for all races in US. From Table 1–6, pg. 7 National Center for Health Statistics, 1993

bir

th r

ate

s p

er

10

00

pop

ula

tion

0.00

50.00

100.00

150.00

200.00

250.00

300.00

60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92

15–19

20–24

25–29

30-34

35–39

40–44

45–49

5-year age groups ofmothers

Live b

irth

s p

er

1,0

00 w

om

en

in s

peci

fied

gro

ups Birth Rates by Age of Mother in U.S. from 1960 to 1993

yearsNational Center for Health Statistics. Vital Statistics of the United States, 1993, vol 1, natality. Hyattsville, Maryland. 1999.

Pregnancy Rates by Age of Mother in U.S. from

1980 to 1999Revised for consistency

with 2000 census.

donors born in the 1950s 1970s P

Median sperm concentration 98 78 (X one million / ml)10th to 90th centile 38.6–218.4 21.0–166.4 0.002

Total number 169.7 129sperm (X one million)10th to 90th centile 52.3–503.9 29–325.8 0.0065

Semen quality of birth cohorts

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



2) The chronic disease model


embryo

neonate

juvenile

adolescent

young adultold adult

senescent

age

stage

fetus

death

Vjuvenile(x)

embryo

fetus

neonate

juvenile

adolescent

young adult

old adult

senescent

death

Vembryo(x)

Vfetus(x)

Vneonate(x)

Vadolescent(x)

Vyoung adult(x)

Vold adult(x)

embryo(x)

senescent(x)

old adult(x)

young adult(x)

adolescent(x)

juvenile(x)

neonate(x)

fetus(x)

Stages

Static Model: t2Stage N

Pre-embryo Embryo Fetus Neonate Juvenile Adolescent Young Adult Old Adult Senescent Death100 0 0 0 0 0 0 0 0 0

ToPre-embryo Embryo Fetus Neonate Juvenile Adolescent Young Adult Old Adult Senescent Death

From Pre-embryo 0 0.8 0 0 0 0 0 0 0 0.2Embryo 0 0 0.9 0 0 0 0 0 0 0.1Fetus 0 0 0 0.98 0 0 0 0 0 0.02Neonate 0 0 0 0 0.99 0 0 0 0 0.01Juvenile 0 0 0 0 0 0.99 0 0 0 0.01Adolescent 0 0 0 0 0 0 0.92 0 0 0.08Young Adult 0 0 0 0 0 0 0 0.55 0 0.45Old Adult 0 0 0 0 0 0 0 0 0.04 0.96Senescent 0 0 0 0 0 0 0 0 0.08 0.92Death 0 0 0 0 0 0 0 0 0 1

Stage n+1Pre-embryo Embryo Fetus Neonate Juvenile Adolescent Young Adult Old Adult Senescent Death

0 80 0 0 0 0 0 0 0 20 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 80 0 0 0 0 0 0 0 20



2) The chronic disease modelThe accordionuniform expansion

expansion at one stageThe bagpipe

simulating changeThe chronic disease model



2) The chronic disease modelThe accordionuniform expansion

Each stage of a lifetime expands and contracts.

simulating change

embryo

fetus

neonate

juvenile

adolescent

young adultold adult

senescent

age

stage

expandedembryo

expandedfetus

expandedneonate

expandedjuvenile

expandedadolescent

expanded

young adult expanded

senescence

expanded

old adult

deathdeathdeathdeathdeath

AccordionStage N Pre-embryo Embryo Fetus Neonate Juvenile Adolescent Young Adult Old Adult Senescent Death

100 0 0 0 0 0 0 0 0 0


From Pre-embryo 0.4 0.4 0 0 0 0 0 0 0 0.2Embryo 0.2 0.3 0.4 0 0 0 0 0 0 0.1Fetus 0.1 0.15 0.2 0.53 0 0 0 0 0 0.02Neonate 0.05 0.075 0.1 0.265 0.5 0 0 0 0 0.01Juvenile 0 0.05 0.06 0.13 0.25 0.5 0 0 0 0.01Adolescent 0 0 0 0.06 0.125 0.25 0.485 0 0 0.08Young Adult 0 0 0 0 0.06 0.125 0.25 0.315 0 0.25Old Adult 0 0 0 0 0 0.06 0.12 0.16 0.04 0.62Senescent 0 0 0 0 0 0 0 0 0.08 0.92Death 0 0 0 0 0 0 0 0 0 1


40 40 0 0 0 0 0 0 0 20 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

40 40 0 0 0 0 0 0 0 20

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death



2) The chronic disease modelThe accordionThe bagpipe

uniform expansionexpansion at one stage

Which stage has the greatest potential for expanding longevity? has the lowest death rate?

simulating change

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

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

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.

Designation IntervalEarly fetal death Under 20 weeks of gestationIntermediate fetal death 20–27 weeks of gestationLate fetal death 28 or more weeks of gestationPerinatal death (1) 28 weeks of gestation to 7th day after birth

(2) 20 weeks of gestation to 28th day after birthNeonatal death Under 28 days after birthPost neonatal death 28 days to end of first year of lifeInfant death Under one year after birth

Fetal death and infant mortality

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

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

Number

of live Under Under Fetal Maternalbirths All ages 1 year 28 days deaths deaths

United States 3,326,632 1,899,597 46,975 32,860 33,053 373

fraction live births 0.0141209 0.0098779 0.0099359 0.0001121

Number of Deaths

Live births, total deaths, infant and neonatal deaths and fetal deaths

juvenile

age

neonate

senescent

old adultyoung adult

adolescent

embryo

fetus

stage

death

extension of the juvenile

stage to later stages of the

lifetime

Bagpipe: bStage N

Pre-embryo Embryo Fetus Neonate Juvenile Adolescent Young Adult Old Adult Senescent Death100 0 0 0 0 0 0 0 0 0


From Pre-embryo 0 0.8 0 0 0 0 0 0 0 0.2Embryo 0 0 0.8 0 0 0 0 0 0 0.1Fetus 0 0 0 0.98 0 0 0 0 0 0.02Neonate 0 0 0 0 0.99 0 0 0 0 0.01Juvenile 0 0 0 0 0.999 0 0 0 0 0.001Adolescent 0 0 0 0 0 0 0 0 0 0Young Adult 0 0 0 0 0 0 0 0 0 0Old Adult 0 0 0 0 0 0 0 0 0 0Senescent 0 0 0 0 0 0 0 0 0 0Death 0 0 0 0 0 0 0 0 0 0


0 80 0 0 0 0 0 0 0 20 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 80 0 0 0 0 0 0 0 20

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Pre-embryo

Embryo

Fetus

Neonate

Juvenile

Adolescent

Young Adult

Old Adult

Senescent

Death

Juvenilization: the expansion of youthful anatomy and physiology to the later stages of a lifetime, i.e., ‘forever young.’

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.

Paedogenesis: “sexual maturity occurs before the organism reaches the full size or relative proportions (shape) of closely related species.”*



2) The chronic disease modelThe accordionThe bagpipe


3) Hypotheses for testing

simulating changeThe accordion: uniform expansionThe bagpipe: expansion at one stage

neoteny the^



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

Genetics: (polygenic) Mendelian control

Epigenetics: NonMendelian heritability

Environment: Directly inducibleHow might a lifetime be juvenilized and a lifespan

lengthened?

Twin studies: Lifespan heritability

Maximum longevity possible or lifespan limits: the compensation effect of mortality


Experimental genetics of so-called model organisms

Pedigrees and familial correlations at the age of death

Juvenile phase spread by acquisition and accumulation of pro-juvenile mutations and elimination or dilution of anti-juvenile and aging Mendelian genes.



Environment: Directly inducibleJuvenile 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”

The stem cell “fountain of youth” or “antithesis of aging,”

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.

“redundant elements that function as backups in the event of failure”


Epigenetics: NonMendelian heritability

Environment: Directly inducible

Juvenile phase expanded by changes that increase robustness and diminution of frailty but are not inherited according to the rubric of Mendelian genetics.


Juvenile phase enhanced by hypothermia, nutritional deprivation and stress (not adversity).

Lamarckian^

Epigenetics:

DNA methylation

Delayed DNA methylation

DNA de-methylation

* Wikipedia, The Free Encyclopedia: http://en2.wikipedia.org/wiki/Main+Page

* 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.

* 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.

http://en2.wikipedia.org/wiki/Main+Page





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?

In sum:

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




Is there a biological explanation?neoteny the

^

Shostak, S., 2004.

*:shostak, s., albany: suny press; 2002

Documents

health statistics

vital statistics

agespecific birth rates

old age

age of mother

yearbirth rates

homo sapiens evolving

yearsnational center