Theories of Aging

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Theories of Aging

• Possible Mechanisms

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3 Criteria of Aging Theories
1. Must occur in all individuals of the
population 2. Produce Changes in function/
structure 3. Changes increase with age
(progressive)
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Change in Structure / Function
Cellular- previous lecture Acellular-
extracellular matrix ground substance fibers c
ollagen (up to 30 of protein) elastin
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3 Catagories of Theories
1. Wear and Tear (Damage) Theory 2.
Physiological/ Chemical Changes 3. Genetically
Programmed (Senescence Genes)
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Wear and Tear Theories
Weismann (1891) Ordinary insults and injuries of
daily living accumulate and decrease function to
some sub-vital level e.g. loss of teeth --gt
starvation molecular level enzymes accumulat
ion of harmful metabolites (cell garbage
theory) e.g. aldehydes, free radicals,
lipofuscins interfere with cell function
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Wear and Tear Theories (cont.)

• finite energy theories
• animals with high metabolic
• rates have shorter life spans
• rats on calorie restrictive diets live longer
• mammals and birds should live shorter
• lives
• People that exercise should live
• shorter lives

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Wear and Tear Theories Refuted

1. Animals in protected environs. have no
change in maximum life span. 2. Time-dependent
changes cannot initiate aging 3. Cellular/
Genetic evidence
Reformulated as Failure to Repair Theories
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Physical/ Chemical Changes
1. Cross Linkage Theory (Post-translational
modification) macromolecules cross linked
(denatured) leading to a decline in
function e.g. proteins- collagen, elastin How
? Disulfide Bonds (cys-cys) Advanced Glycation
End-Products (AGEs) accelerated in
diabetics DNA cross-linkage occurs also
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Physical/ Chemical Changes
2. Altered Protein Theory protein folding no
change in primary structure decline in catalytic
activity with age e.g. enolase in
nematodes denature/renature experiments shape
change can be reversed increased carbonyl
content (ketones, aldehydes) of proteins
(oxidative)
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Physical/ Chemical Changes
3. Free Radical Theory (Oxidative Damage) Free
Radicals contain unpaired electrons making them
highly reactive therefore only exist for a
short time. e.g. Superoxide, hydroxyl ,
peroxide Lipid peroxidation- damage to cell
membranes especially mitochondrial Protein cross
linkage DNA damage Antioxidants - Vitamins A, C,
E, Cellular Defenses- Catalase, Superoxide
Dismutase
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Reactive Oxygen Species
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Aging By Program
Assumptions Biological Clock Molecular Clock-
the Telomere ? Life Span Inheritable Twin
Studies Biological Clock Hypothalamus Decline
in Signal Decreased Sensitivity to
Feedback Programmed senescence does not require
central control - cell culture evidence
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Aging By Program
Gene Mutation Theory- accumulation of somatic
cell mutations leads to a decline in
function Liver cells of older mice have
more mutations than young Short life span
strains have more mutations at same age DNA
repair mechanisms Decrease in repair function??
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Aging By Program
Gene Theory One or more harmful genes active
only later in life Evidence? Microarray
analysis Death Genes or Gerontogenes
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Microarray Analysis C. elegans
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Evolutionary Theories
Disposable Body Theory- Post-reproductive
individual has no benefit No genes favoring long
life-span should evolve Genes do not cause
aging, but fail to prevent it from
happening Antagonistic Pleiotropy Theory- Genes
that promote success at a young age have a
negative effect at old age Late-acting error
theory- errors occuring before reproduction
eliminated by natural selection no selective
pressure to eliminate them after