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AGEING Basic terms, epidemiology, theories of ageing and the genetic background of ageing

AGEING Basic terms, epidemiology, theories of ageing and the genetic background of ageing. LECTURE FROM PAT H OLOGIC AL PHYSIOLOGY OLIVER RÁCZ INSTITUTE OF PAT H O LOGICAL PHYSIOLOGY MEDICAL SCHOOL, ŠAFÁRIK UNIVERSITY, KOŠICE. WHAT IS AGEING ?. 1973 – m y first assay on ageing

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AGEING Basic terms, epidemiology, theories of ageing and the genetic background of ageing

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  1. AGEINGBasic terms, epidemiology, theories of ageing and the genetic background of ageing LECTURE FROM PATHOLOGICALPHYSIOLOGY OLIVER RÁCZ INSTITUTE OF PATHOLOGICAL PHYSIOLOGY MEDICAL SCHOOL, ŠAFÁRIK UNIVERSITY, KOŠICE agedent.ppt

  2. WHAT IS AGEING ? • 1973 – my first assay on ageing • 1987 – you can’t study aging, it just happens • Tear and wear or a programme ? • 1999, TIME - can I live to be 125 ? (or 300) Don’t do it! (quality of life) New problem – did not exist until XIXth century(?) Death in nature mostly is not (or very distinctly) associated with ageing agedent.ppt

  3. THE ECONOMICAL DIMENSIONOF AGING(% of people > 60 y) • REGION1990 2030 • OECD 19 33 • POSTSOC COUNTRIES16 24 • SOUTH AMERICA 07 16 • AFRICA 05 08 • ASIA WITHOUT CHINA07 14 • CHINA09 23 agedent.ppt

  4. WHAT IS AGEING ? New(medical) problem – did not exist until XIXth century Death in nature mostly is not (or very distinctly) associated with ageing A very old problem Tithonus, a lover of Goddes Eos, after a quarrel of Eos with Zeus acquired immortality but not eternal youthfulness!!! (see also Swift’s Gulliver and a lot of other literature, alchemy, etc.) Or Henrietta Lacks, 33 y old mother of 5 children in 1951 ??? agedent.ppt

  5. WHAT IS AGEING ? • GERONTOLOGY (SCIENCE) & GERIATRICS (PRACTICAL MEDICINE) • WHO: • Middle age45 - 59 y. • Presenium 60 - 74 y. • Senium – old age 75 - 90 y. • Very old age > 90 y. • PRACTICE • Old age> 65 y. agedent.ppt

  6. THE FEATURES OF AGEING • Irreversible changes of biological macromolecules • Gene dysregulation • Decreased metabolic capacity • Decrease of physiological functions • Decreased adaptability in stress situations and pathological conditions • Higher occurrence of diseases, multimorbidity • Decreased quality of life • Increased mortality agedent.ppt

  7. THE MATHEMATICS OF AGEING • MORTALITY(“J”) • LIFE EXPECTANCY (AVERAGE OR MEDIAN LIFE SPAN, Gompertz) • AGE PYRAMID • MAXIMAL LIFE SPAN (MLSP) agedent.ppt

  8. AVERAGE LIFE SPAN LIFE EXPECTANCY AT BIRTH • For a cohort of people at birth (1000): • Point of time (years) when 50 % already passed, 50 % yet lives • For an individual: • 50 % probability to live so long • Variable – short time changes are possible, too • Does not depend on old generation !!! • Continuous rise in the past – luring menace of decrease (AIDS, obesity) agedent.ppt

  9. GOMPERTZ CURVE agedent.ppt

  10. LIFE EXPECTANCY AT BIRTH, XXth CENTURY - USA 2000 75 YEARS 1900 50 YEARS agedent.ppt

  11. AVERAGE LIFE SPAN, EXPLANATION • 100 HEALTHY PEOPLE V75 – 95y. (average = 85 y) • 10 more Vin age 25 y. (average = 79 y) • 10 moreVin age 70 y. (average = 84 y) IN PAST – PERINATAL AND INFANT MORTALITY, PANDEMIES (PEST XVI-XVII cent., FLU 1918), WARS TODAY: CHD, OBESITY, MALIGNANCIES, ACCIDENTS, AIDS agedent.ppt

  12. LIFE EXPECTANCY • AT BIRTH (75) BUT ALSO LATER • At 50, 75, 90… • Women > men (also in nature, XX > X) • Social status • Smokers < nonsmokers, obese < lean, etc. agedent.ppt

  13. AGE PYRAMID agedent.ppt

  14. MAXIMUM LIFE SPANBiological constant but species specific agedent.ppt

  15. THE NUMBER OF CENTENARIANS IN GERMANY • 1938 4 • 37/37 • 1975 146 • 15/9,7 • 1990 1416 • 5/1,65 • 1995 2333 • 7/1,66 • 2002 3883 agedent.ppt

  16. SPECIES MAYFLY C. ELEGANS DROSOPHILA ZEBRAFISH, MOUSE DOG, CAT MAN, GIANT TORTOISE RANGE < 1 DAY WEEK – MONTH MONTH – YEAR YEAR – DECADE DECADE CENTURY VARIATION IN MAXIMUM LIFE SPAN ACROSS SPECIES agedent.ppt

  17. AGEING AND SCIENCE • Tear and wear ? • Programme ? apoptosis, thymus involution differences in MLSP of different species (mouse – man) progeric symdromes are rare hereditary diseases replicative ageing and telomeres mutations (in experiments) connected with prolonged life span „The oldest old“ • NATURE OR NURTURE ? agedent.ppt

  18. TEAR AND WEAR OR PROGRAMME ? AGING IS NOT LIKELY TO BE REGULATED IN THE SAME PROGRAMMED WAY AS DEVELOPMENT Kirkwood, 1982, 1996 agedent.ppt

  19. TEAR AND WEAR OF WHAT AND HOW ? • Biochemical changes of proteins (no) • Membrane structure and function (no) • Somatic mutations(no) • Theory of error catastrophe – Orgel, 1963? • Deterioration of control and reparation mechanism of replication, transcription and translation • OXPHOS – the weakest part of the whole chain are the MITOCHONDRIA agedent.ppt

  20. TEAR AND WEAR, THE CAUSE ? • Rate of living (an explanation of different MLSP despite similar composition of tissues) • Oxygen consumption of mice and men • Man (80 kg)>> mouse (30 g) but • 1 g mouse tissue >> 1 g human tissue • Maximum life span • Man >> mouse !!! agedent.ppt

  21. TEAR AND WEAR, THE CAUSE ?J. Verne: Mr. Ox and his servant Ygen • Rate of living (burning the candle) • Oxygen consumption (ml/g/min) is in inverse relationship with life span • Oxygen and its reactive forms (ROS) • The theory is true but only in general terms • The other side of the story: • ANTIOXIDANT SYSTEMS !!! agedent.ppt

  22. EVOLUTION OF AGEINGUNICELLULAR Sacharomyces cerevisiae (yeast) Replicative ageing regulated through genes Cells of higher animals Fibroblasts and other mitotic cells – correlation with age of the individuum and MLSP (Hayflick, 1961; Dolly 1998) Telomere shortening during division (association with carcinogenesis and telomerase) agedent.ppt

  23. REPLICATIVE AGEING agedent.ppt

  24. EVOLUTION OF AGEING Caenorhabditis elegans (simple multicellular) • age1 – prolonging of MLSP by 110 % Resistanceagainst oxidants, increased temperature, UV rays Activity of SOD andcatalase • Daf2,23,28 mutations • Genes of signal transduction ! STRESS RESPONSE GENES • spe26 (gamete production), clk1 (internal rytmus) agedent.ppt

  25. EVOLUTION OF AGEING Drosophila melanogaster • Different lines with prolonged life span Resistanceagainst oxidants Resistanceagainst starvation and dehydratation But also flies in small boxes and without wings (?) • Transgenic drosophila +SOD = 0; +CAT = 0; +(SOD & CAT) = 30% agedent.ppt

  26. EVOLUTION OF AGEING Mammals, primates, man • Very important role of neuroendocrine and immune system • Economics (cost/benefit) of complex system • In very complicated systems the „costs“ of maintenance are inappropriate high („STK“ system of cars) • Nakano - lipofuscin begins to accumulate after reproductive period agedent.ppt

  27. EVOLUTION OF AGEING • Caloric restriction and longevity • Works in rats, mice... (different life cycle) • Okinawa • CALERIE = Comprehensive assesment of Long-term Effects of Reducing Intake of Energy • Slowing down of metabolism (rate of living) or something more complicated? • Sirtuin genes (7, DNA stabilisation, copy fidelity) • Resveratrol from red wine(and other plant molecules) activates them agedent.ppt

  28. THE OLDEST OLD SELECTIVE SURVIVAL ? Mortalityover 90 – turn on the curve men>women Incidence of Alzheimer disease Short period before death Which genes? APO E ?, ACE ? agedent.ppt

  29. THE OLDEST OLD • TIZIANO V 1477 - 1576 98 – PIETA • VERDI G 1813 - 1902 80 – FALSTAFF • PICASSO P 1881 - 1973 86 – LE COUPLE • CHURCHILL, CASALS, KŇAZOVICKÝ... • QUEEN MOTHER, MOJSEJEV (102) • JOHN GLENN, 1922 (1962, 1999 and his 96 years old friend) agedent.ppt

  30. PRIMARY AND SECUNDARY AGEING ? Sooner or later something breaks down! • BRAIN – ALZHEIMER (AND OTHER DEGENERATIVE) DISEASES • VESSELS – ATHEROSCLEROSIS, CORONARY DISEASE • REGULATION OF BLOOD PERFUSION– HYPERTENSION • REGULATION OF METABOLISM – DIABETES • BONES AND JOINTS– OSTEOPOROSIS • SENSES – SIGHT AND HEARING ARE DECISIVE IN NATURE agedent.ppt

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