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  1. 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

  2. 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

  3. What is lifespan? • Averagelifespan:Ageatwhich 50% of cohort has died (muchcontroledbyenvironment) • Maximum life-span: Essentiallytheage of thelastsurvivor (muchcontrolledbygenetics)

  4. 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)

  5. Approaches in senescence research • Three major branches: • Biometricbranch:complex, difficulttoperformintervention • Inductivebranch:few, simple, universalmechanisms • Regeneration and renewalbranch:focusonreplacementandremodeling

  6. August Weismann’sconcepts on aging • Adaptiveconcept:Agingevolvedtocleansethepopulationfrom old, non-reproductiveconsumers • Non-adaptiveconcept:Aging is duetogreaterweightonearlysurvival / reproductionratherthanvigoratlaterages

  7. Pioneers of aging research include • DenhamHarman • George Sacher • Nathan Shock • Bernard Strehler • Alex Comfort • John Maynard Smith • ZhoresMedvedev • PaolaTimiras • LoenardHayflick • George Martin

  8. 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)

  9. Major groups of aging theories • Evolutionarytheories • Programmedtheories • Damagetheories • General formulations • Individualmechanisms • Stressinducedprematuresenescence (SIPS) • Beyondmolecularbiology of aging

  10. Major groups of aging theories,in depth I Evolutionary theories ofliving and longevity • Programmed death theory • Mutation accumulation theory • The antagonistic pleiotropy theory

  11. 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)

  12. 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

  13. 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

  14. Major groups of aging theories,in depth V Beyond molecular biology of aging • Thermodynamics of aging • Reliability theory • Rate of living theory

  15. Theory of antagonistic pleitropy • Trade-offbetweenfertility and longevitygenes • Optimalconditions: investingrowth and reproduction • Restrictiveconditions: shutoffreproduction, investinsomaticmaintenance and survival

  16. 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)