EVOLUTI ONARY THEORI ES

Cell Development and Cellular

Senescence
Aging and Darwins Evolutionary Theory
Aging theories try to explain developmental
processes in the context of natural selection
Patterns of aging across species
Give theoretical predictions that can be experimental
tested.
Initial Theories
August Weismann (1882 & 1891)
There is an evolutionary advantage for the species (not the
individual) to have a limited life span.
Older individuals negative selection of older members of
species so that they cannot compete for food and resources
Life span would be dependant of the number of cell
generations that is the norm for a specific species
Hayflick (1961) cellular senescence
Suggested that resources were invested for the germ line as
opposed to the soma
Kirkwood 1977 disposable soma theory
Contemporary Theories of Aging
Mutation Accumulation Theory
Peter Medawar (1952)




Antagonistic Pleiotropy
George C Williams (1957)
Mutation Accumulation Theory
Aging is a byproduct of natural selection
Has no adaptive traits
Mutations in a population accumulate because there
is no evolutionary mechanism to remove detrimental
effects seen only in old members
Reproduction is age dependant
Deleterious genes expressed young are selected against to
maintain reproductive fitness
Deleterious genes expressed later in life are neutral and are
passed on to future generations

Mechanisms
3 categories
1) gradual and appear late in life (cellular and metabolic
damage- oxidative damage, DNA mutations, telomere
shortening)
2) linked to young adulthood (cellular senescence and caloric
restriction)
3) external mechanisms (infections and pathogens)
Antagonistic Pleiotropy
Genes are beneficial early but not later in life and are
called pleiotropic genes.
Is based on 2 assumptions
May have an effect on several genes (pleiotropy)
Effects fitness in an antagonistic way
Explains reproductive costs
Maximizes vigor in youth at a cost at older ages
Can explain age-related diseases
However, these genes will stay in the reproductive
pool even though they have deleterious effects later
in life

Examples:
Cellular senescence versus cancer
Hormones used to promote reproductive health can cause
cancer later in life (i.e. estrogen)

The differences between the major theories is that in
one (accumulation of mutations), deleterious genes
are passively retained, whereas in the other
(antagonistic pleiotropy), deleterious genes are
actively selected for.
Paradoxical Antagonistic Pleiotropy
Harmful at younger ages but beneficial at older
Disposable Soma Theory
Kirkwood and Holiday (1979)
Proposes that molecular and cellular damage accumulates in the
soma to cause aging. This is the result of maintenance of
reproductive fitness at the expense of the soma as one ages. A set
of genes are antagonistically pleiotropic. These genes repair and
maintain genetic integrity early on but accumulate mutations and
increasingly fail to repair genetic systems as one ages.