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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011.

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Basics of molecular gerontology – Aging theories

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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 Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011


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 Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

Krisztián Kvell

Molecular and Clinical Basics of Gerontology – Lecture 28

Basics of moleculargerontology –Agingtheories


Basics of molecular gerontology aging theories

What is lifespan?

  • Averagelifespan:Ageatwhich 50% of cohort has died (muchcontroledbyenvironment)

  • Maximum life-span: Essentiallytheage of thelastsurvivor (muchcontrolledbygenetics)


Basics of molecular gerontology aging theories

Correlation between body mass and lifespan

1000

100

tmax (yrs)

10

y = 5.58x0.146

r2 = 0.340

1

1.E+10

1.E+08

1.E+06

1.E+04

1.E+02

1.E+00

M (g)


Basics of molecular gerontology aging theories

Approaches in senescence research

  • Three major branches:

    • Biometricbranch:complex, difficulttoperformintervention

    • Inductivebranch:few, simple, universalmechanisms

    • Regeneration and renewalbranch:focusonreplacementandremodeling


Basics of molecular gerontology aging theories

August Weismann’sconcepts on aging

  • Adaptiveconcept:Agingevolvedtocleansethepopulationfrom old, non-reproductiveconsumers

  • Non-adaptiveconcept:Aging is duetogreaterweightonearlysurvival / reproductionratherthanvigoratlaterages


Basics of molecular gerontology aging theories

Pioneers of aging research include

  • DenhamHarman

  • George Sacher

  • Nathan Shock

  • Bernard Strehler

  • Alex Comfort

  • John Maynard Smith

  • ZhoresMedvedev

  • PaolaTimiras

  • LoenardHayflick

  • George Martin


Basics of molecular gerontology aging theories

The family tree of aging theories

Aging theories

Evolutionary theories of living and longevity

Programmed theories

Damage theories

Beyond molecular biology of aging

General formulations

Individual mechanisms

Stress-induced premature senescence (SIPS)


Basics of molecular gerontology aging theories

Major groups of aging theories

  • Evolutionarytheories

  • Programmedtheories

  • Damagetheories

    • General formulations

    • Individualmechanisms

    • Stressinducedprematuresenescence (SIPS)

  • Beyondmolecularbiology of aging


Basics of molecular gerontology aging theories

Major groups of aging theories,in depth I

Evolutionary theories ofliving and longevity

  • Programmed death theory

  • Mutation accumulation theory

  • The antagonistic pleiotropy theory


Basics of molecular gerontology aging theories

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)


Basics of molecular gerontology aging theories

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


Basics of molecular gerontology aging theories

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


Basics of molecular gerontology aging theories

Major groups of aging theories,in depth V

Beyond molecular biology of aging

  • Thermodynamics of aging

  • Reliability theory

  • Rate of living theory


Basics of molecular gerontology aging theories

Theory of antagonistic pleitropy

  • Trade-offbetweenfertility and longevitygenes

  • Optimalconditions: investingrowth and reproduction

  • Restrictiveconditions: shutoffreproduction, investinsomaticmaintenance and survival


Basics of molecular gerontology aging theories

Correlation ofmorbidity ratesand age

  • Morbidity rate

  • increase peaksat 60y,

  • deceleratesafter 80y,

  • remains linearafter 110y

60

Sinusitis

Asthma

50

Renal disease

Arthritis

40

Diabetes

Cancer

30

% with disease

Cardiac disease

20

10

0

0

20

40

60

80

100

Age (years)


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