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