Transcript Evolution and Biology II

Evolution, Biology and Aging
Chapter 2
Werner’s Syndrome and The
Curious Case of Benjamin Button
Evolution and Biology
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Biological Theories of Aging
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Evolutionary Perspectives on Aging
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Genetics and Aging
I. Biological Theories of Aging
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Rate-of-Living Theories
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Cellular Theories
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Programmed Cell Death Theories
Rate-of-Living Theories and
Research (Programmed Model)
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Animal variations in size and heart-rates, etc. seem
to be roughly associated with life spans – e.g., mice,
dogs, humans, tortoises = some sort of metabolic
limit?
Delaying reproduction in fruit flies leads to longer life,
hibernation can lengthen life, etc.
Recent work on caloric restriction suggests it may
lengthen life, perhaps in similar ways, by slowing
metabolism
Cellular Theories of Aging –
Programmed Telomere Shortening
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Body cells can only divide and reproduce a limited number of
times – varies by species – called the Hayflick limit, mice =
15, humans = 50, tortoise = 110
Telomeres at end of chromosomes are needed to reproduce
successfully, but get shorter each time until gone
Telomerase is an enzyme which will allow these to maintain
length, but is usually switched off in cells. Cancers turn on the
genes regulating telomerase, and thus cells keep replicating
Embryonic stem cells also do this, have potential to develop
in various ways and over long time – most specialized cells can’t
Chromosomes with Telomeres
Cellular Theories – Oxidation and
Free Radicals (Random Theories)
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Free radicals are molecules produced as part of cell’s metabolic
processes, when oxygen combines with cell products
Oxygen plays a critical role in metabolism, but free radicals
which are produced are bad…Like rust, they damage genes and
chromosomes, immune functions, increase susceptibility to
disease.
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Lowered production of free radicals may be pathway through
which some of the other factors, like caloric restriction, operate
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Various foods and chemicals may serve as antioxidants and
may somewhat lower free radical production
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+ Cross-linkage theory – glucose and protein stickiness
leading to stiffening of cells
Programmed Cell Death
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Cells at end of their life span limits go through
process called “apoptosis” which means
programmed death
Possible that there is a genetic program that
underlies this in some way, and which could explain
many of cellular effects
Implications of this might be the possibility of
reversal of this program in strategic way
Key point is that various theories are probably
linked together in some ways, each may capture a
part of larger mechanism of how aging takes place
II. Evolutionary Perspective
on Aging - Outline
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Darwin’s theory of evolution
Some general models of evolutionary
influences on adulthood and aging
Genetics and aging
Evolution on the Far Side
Darwin’s Theory of Evolution –
3 Principles
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Population variation in
body structure and
behavior
Method of reliable
inheritance – Mendel’s
genes
Natural selection for
fitness among variants
– too many offspring,
depends on
reproductive success
Some General Ideas of Evolutionary
Processes and Aging
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Lifespan = pre-reproductive + reproductive
periods vs. post-reproductive period
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Evolution operates most directly on genes that
regulate development til end of reproductive period
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Post-reproductive period not regulated as much by
evolution = many diseases: ALS, some cancers,
Huntington’s chorea, Alzheimer’s, that have not been
selected against because not expressed earlier on
Gene effects can be complex: good early, and then
bad later (antagonistic pleiotropy), May be
selected for – APO E4 gene linked to Alzheimer’s,
but also protects against diarrhea in kids
Average Lifespan over Human
History
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Only in last century
has living into
post-reproductive
period become
common
80
70
60
50
40
30
20
10
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Previously, many
diseases of late life
were usually not
expressed since
people died early
0
Prehistory
100
1900
2000
Implications of Aging in
Historical Context
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Control of infectious diseases of childhood and
death in childbirth have made big changes in
lifespan since 1900
We thus get to a lot of physical problems – immune
system, skeletal system, sensory problems – that
ancestors usually didn’t get to at all because they
died before they came along!
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Development is more heavily buffered in earlier part
of life span, much more variable with age in later life
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However, various genes can be expressed at any
point in life course
III. Genetics 001
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DNA – 20,000 or so genes on 23 pairs of
chromosomes in humans
Protein coding genes (2-3 %) vs. regulator genes
(?%) and non-coding “junk” (no longer active, ?%)
Genotypes vs. phenotypes – e.g., recessive gene
defects, such as Werner’s Syndrome – only
expressed when both parents have defect, parents
themselves are carriers only
Studying Genetic Influences
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Behavior genetics research – proportion of
variance (of 100%) in a trait due to genes
Twin studies – MZ versus DZ twins
Several major European studies involving
thousands of twins across lifespan
Werner’s Syndrome – An Inherited
Premature Aging Disorder
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Rare, recessive disorder
– need 2 copies to
express, on
Chromosome pair 8
Begins in adolescence,
aging emerges by 30,
twice normal rate
Major problem is
mutation in an enzyme
that is supposed to
repair DNA in cell –
consistent with free
radical theory
What is Evidence with Regard
to Longevity and Genetics?
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About 30% of variation in these samples in
life expectancy due solely to genes
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Good functioning (younger biological age)
in later life is also partly heritable
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Blood pressure, pulmonary function, diabetes,
bone loss, muscle strength, walking speed –
all these functions have substantial
heritability
Gene by Environment Interactions
(Genes Shape Environmental Effects)
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APOE gene on Chromosome 19 has 3 variants – e4 is
risk (15x) for earlier Alzheimer’s expression, e2 is
protective, e3 is neutral
This gene affects repair of neuronal damage, e4
variant is bad at this. Carriers do not benefit from
environmental factors like exercise, education in
preventing Alzheimer’s onset (Gene x Environment
interaction)
Another Alzheimer’s gene carried on X chromosome,
women more susceptible
Epigenetic View of Gotlieb
(Environment Shapes Genes)
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Genes don’t just rule, however, environment
influences processes of evolution and heredity
Ex., herding cultures in last 6,000 years and
lactose-tolerance gene; this gene remains
switched on after weaning in these populations
because they depended on milk
This gene has been selected for in the “switched on”
variant in several populations at higher rate, because
of environmental life style
Shows how evolutionary processes continue today,
shaped by culture – in this case, agriculture