1. Evolution, Biology and Aging
Chapter 2

2. Werner’s Syndrome and The Curious Case of Benjamin Button

3. Evolution and Biology Biological Theories of Aging
Evolutionary Perspectives on Aging
Genetics and Aging

4. I. Biological Theories of Aging
Rate-of-Living Theories
Cellular Theories
Programmed Cell Death Theories

5. Rate-of-Living Theories and Research (Programmed Model)
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

6. Cellular Theories of Aging – Programmed Telomere Shortening
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

7. Chromosomes with Telomeres

8. Cellular Theories – Oxidation and Free Radicals (Random Theories)
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.
Lowered production of free radicals may be pathway through which some of the other factors, like caloric restriction, operate
Various foods and chemicals may serve as antioxidants and may somewhat lower free radical production
+ Cross-linkage theory – glucose and protein stickiness leading to stiffening of cells

9. Programmed Cell Death
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

10. II. Evolutionary Perspective on Aging - Outline
Darwin’s theory of evolution
Some general models of evolutionary influences on adulthood and aging
Genetics and aging

11. Evolution on the Far Side

12. Darwin’s Theory of Evolution – 3 Principles
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

13. Some General Ideas of Evolutionary Processes and Aging
Lifespan = pre-reproductive + reproductive periods vs. post-reproductive period
Evolution operates most directly on genes that regulate development til end of reproductive period
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

14. Average Lifespan over Human History
Only in last century has living into post-reproductive period become common
Previously, many diseases of late life were usually not expressed since people died early

15. Implications of Aging in Historical Context
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!
Development is more heavily buffered in earlier part of life span, much more variable with age in later life
However, various genes can be expressed at any point in life course

16. III. Genetics 001
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

17. Studying Genetic Influences
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

18. Werner’s Syndrome – An Inherited Premature Aging Disorder
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

19. What is Evidence with Regard to Longevity and Genetics?
About 30% of variation in these samples in life expectancy due solely to genes
Good functioning (younger biological age) in later life is also partly heritable
Blood pressure, pulmonary function, diabetes, bone loss, muscle strength, walking speed – all these functions have substantial heritability

20. Gene by Environment Interactions (Genes Shape Environmental Effects)
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

21. Epigenetic View of Gotlieb (Environment Shapes Genes)
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