Basics of molecular gerontology – Aging theories
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Transcript of Basics of molecular gerontology – Aging theories
Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
BASICS OF MOLECULAR GERONTOLOGY –AGING THEORIES
Krisztián KvellMolecular and Clinical Basics of Gerontology – Lecture 28
Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011
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• Average lifespan:Age at which 50% of cohort has died (much controled by environment)
• Maximum life-span: Essentially the age of the last survivor (much controlled by genetics)
What is lifespan?
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y = 5.58x0.146
r2 = 0.340
t max
(yrs
)
1000
100
10
11.E+00 1.E+02 1.E+04 1.E+06 1.E+08 1.E+10
M (g)
Correlation between body mass and lifespan
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Three major branches:• Biometric branch:
complex, difficult to perform intervention• Inductive branch:
few, simple, universal mechanisms• Regeneration and renewal branch:
focus on replacement and remodeling
Approaches in senescence research
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• Adaptive concept:Aging evolved to cleanse the population from old, non-reproductive consumers
• Non-adaptive concept:Aging is due to greater weight on early survival / reproduction rather than vigor at later ages
August Weismann’sconcepts on aging
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• Denham Harman• George Sacher• Nathan Shock• Bernard Strehler• Alex Comfort
• John Maynard Smith• Zhores Medvedev• Paola Timiras• Loenard Hayflick• George Martin
Pioneers of aging research include
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The family tree of aging theories
General formulations
Individual mechanism
s
Stress-induced premature senescence
(SIPS)
Damage theories
Evolutionary theories of living
and longevity
Beyond molecular
biology of agingProgrammed theories
Aging theories
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• Evolutionary theories• Programmed theories• Damage theories
- General formulations- Individual mechanisms- Stress induced premature senescence
(SIPS)• Beyond molecular biology of aging
Major groups of aging theories
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Major groups of aging theories,in depth IEvolutionary theories ofliving and longevity• Programmed death theory• Mutation accumulation theory• The antagonistic pleiotropy theory
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Major groups of aging theories,in depth II
Programmed theories• Immune system compromise• Neurological degeneration• Hormonal theory of aging• The genetic clock
(programmed epigenomic theory)
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Major groups of aging theories,in depth III
General formulations• Misrepair accumulation theory• Waste accumulation theory of aging• Error catastrophe theory• Wear and tear theory
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Major groups of aging theories,in depth IV
Individual mechanisms• Chronic or excess inflammation• Mitochondrial damage• Methylation• Glycation• Oxidative damage-Free radical• Somatic DNA damage/mutation
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Major groups of aging theories,in depth VBeyond molecular biology of aging• Thermodynamics of aging• Reliability theory• Rate of living theory
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• Trade-off between fertility and longevity genes
• Optimal conditions: invest in growth and reproduction
• Restrictive conditions: shut off reproduction, invest in somatic maintenance and survival
Theory of antagonistic pleitropy
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AsthmaRenal disease
Diabetes
Cardiac disease
Arthritis
Cancer
Correlation ofmorbidity rates and age
Morbidity rate• increase
peaksat 60y,• decelerates
after 80y,• remains
linearafter 110y0 20 40 60 80 100
10
30
50
0
20
40
60
% w
ith d
iseas
e
Age (years)
Sinusitis