Biology of Aging

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Biology of Aging
Mike Gustin Alumni College 2005

• Grandmother effect
• Aging Brain
• Caloric restriction
• Aging in animals
• Red wine effect
• Young blood

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Mammalian life histories
Maturation is delayed Reproduction is slow Adults
grow old
Maturation is quick Fertility is high Adults die
young
Small rodents
Humans
Other primates
Dogs cats
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The Grandmother Effect
Care flows from old to young, increasing fitness
of young.
Lahdenpera et al, Nature 428, p 178-181, 2004
Analyzed multiple generations Slow-growing
community in Finland 537 women born
in period 1702-1823 6,002
grandchildren Fast-growing community in Canada
3,290 women born in period 1850-1879
100,074 grandchildren
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Lahdenpera et al, Nature 428, p 178-181, 2004
Mother Dead Or Alive?
Offspring (M,F)
grandchildren
Measurements
Fecundity grandchildren
LRS grandchildren living to age 15
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Presence of post- reproductive mother alters
reproductive fitness of offspring
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Conclusions

• Both sons and daughters with a living mother past
  menopause
• Had children sooner
• Had children at shorter intervals
• Raised more children to adulthood
• These differences are independent of
• Differences in wealth
• Offspring sex
• Number of competing siblings
• Birth order
• Mothers age (or potential age)

Lahdenpera et al, Nature 428, p 178-181, 2004
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Finland
Canada

• Life events
• Average age at first grandchild
• 5. Average age of last grandchild
• Average age when half of grandchildren
• produce great-grandchildren
• Dagger Average age at death post-reproduction

Mortality rate increases abruptly within 5-10 yr
after birth of last grandchild
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Patterns of gene activity in human brains change
with age
Lu et al, Nature 429, 883-891, 2004
Age for each of 30 people at death
Genes active in old age
Genes active in youth
200 genes per column
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Stress response genes are more active in older
brains
Selective damage of genes during aging
Lu et al, Nature 429, 883-891, 2004
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Chromosome (DNA)
gene
Food
damage
Oxidants (by-product)
Metabolism
RNA
damage
protein
Energy
Work (nerve, muscle, etc function)
Aging is accumulation of damage caused by oxidants
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Changing lifestyle can increase lifespan
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Caloric restriction increases lifespan in many
creatures
Male rhesus monkeys CR males half the mortality
rate of control males
Roth at al, Science 297, p811, 2002
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Caloric restriction increases life span of many
creatures

• Primates
• Rodents
• Birds
• Fish
• Fruitflies
• Worms
• Yeast

Mair et al, Scence 301, p1731-1733, 2003
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Pathways controlling lifespan
Insulin
Caloric Restriction
Insulin receptor
Stress
FOXO
SIRTUIN
Longer lifespan
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Pathways controlling lifespan
Insulin
Caloric Restriction
Insulin receptor
Red wine effect (resveratrol)
Stress
FOXO
SIRTUIN
Longer lifespan
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Dividing cells have a two phase response to DNA
damage
Damage to DNA by oxidants
sensor
Stop cell growth
Damage repaired?
Repair damage
(waiting period)
YES resume normal cell functions
NO cell commits suicide
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SIRTUIN promotes repair and not death of cells
upon stress
repair
death
Brunet et al, Science 303, p2011-2015, 2004
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Flavenoids (polyphenols) such as reveratrol
activate SIRTUIN and increase lifespan
Effect on SIRTUIN activity
Effect on yeast lifespan
Howitz et al, Nature 425, p191-196, 2003
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Resveratrol mimics caloric restrictions
effect on lifespan
Resveratrol effect requires SIRTUIN
WT normal yeast
R - resveratrol
CR caloric restriction
Howitz et al, Nature 425, p191-196, 2003
sir2 SIRTUIN mutant
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Is old age irreversible?
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Rejuvenation of aged progenitor cells by
exposure to a young systemic environment
Conboy et al, Nature 433, 760-764 Feb 17, 2005
Experiment join blood supply of young mouse to
that of old mouse (parabiosis)
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Heterochronic parabiosis restores muscle
regeneration and muscle stem cell activation in
aged animals
Young serum rejuvenates activation of aged muscle
satellite cells
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Heterochronic parabiosis enhances proliferation
of aged liver progenitor cells
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Biology of Aging
Mike Gustin Alumni College 2005

• Grandmother effect
• Aging Brain
• Caloric restriction
• Aging in animals
• Red wine effect
• Young blood

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Sources

• Google search for Rice Bios 201
• Go to bottom of page
• Click on Alumni College 2005 and sources