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Agedent.ppt1 AGEING Basic terms, epidemiology, theories of ageing and the genetic background of ageing LECTURE FROM PATHOLOGICAL PHYSIOLOGY OLIVER RÁCZ.

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Presentation on theme: "Agedent.ppt1 AGEING Basic terms, epidemiology, theories of ageing and the genetic background of ageing LECTURE FROM PATHOLOGICAL PHYSIOLOGY OLIVER RÁCZ."— Presentation transcript:

1 agedent.ppt1 AGEING Basic terms, epidemiology, theories of ageing and the genetic background of ageing LECTURE FROM PATHOLOGICAL PHYSIOLOGY OLIVER RÁCZ INSTITUTE OF PATHOLOGICAL PHYSIOLOGY MEDICAL SCHOOL, ŠAFÁRIK UNIVERSITY, KOŠICE

2 agedent.ppt2 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

3 agedent.ppt3 THE ECONOMICAL DIMENSION OF AGING (% of people > 60 y) REGION19902030 OECD1933 POSTSOC COUNTRIES1624 SOUTH AMERICA0716 AFRICA0508 ASIA WITHOUT CHINA0714 CHINA0923

4 agedent.ppt4 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 ???

5 agedent.ppt5 WHAT IS AGEING ? GERONTOLOGY (SCIENCE) & GERIATRICS (PRACTICAL MEDICINE) WHO: –Middle age 45 - 59 y. –Presenium60 - 74 y. –Senium – old age75 - 90 y. –Very old age> 90 y. PRACTICE –Old age> 65 y.

6 agedent.ppt6 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

7 agedent.ppt7 THE MATHEMATICS OF AGEING MORTALITY (“J”) LIFE EXPECTANCY (AVERAGE OR MEDIAN LIFE SPAN, Gompertz) AGE PYRAMID MAXIMAL LIFE SPAN (MLSP)

8 agedent.ppt8 AVERAGE LIFE SPAN LIFE EXPECTANCY AT BIRTH vFor 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 vVariable – short time changes are possible, too v Does not depend on old generation !!! v Continuous rise in the past – luring menace of decrease (AIDS, obesity)

9 agedent.ppt9 GOMPERTZ CURVE

10 agedent.ppt10 LIFE EXPECTANCY AT BIRTH, XXth CENTURY - USA 1900 50 YEARS 2000 75 YEARS

11 agedent.ppt11 AVERAGE LIFE SPAN, EXPLANATION 100 HEALTHY PEOPLE  75 – 95 y. (average = 85 y) 10 more  in age 25 y. (average = 79 y) 10 more  in 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 

12 agedent.ppt12 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.

13 agedent.ppt13 AGE PYRAMID

14 agedent.ppt14 MAXIMUM LIFE SPAN Biological constant but species specific

15 agedent.ppt15 THE NUMBER OF CENTENARIANS IN GERMANY 19384 –37/37 1975146 –15/9,7 19901416 –5/1,65 19952333 –7/1,66 20023883

16 agedent.ppt16 VARIATION IN MAXIMUM LIFE SPAN ACROSS SPECIES SPECIES MAYFLY C. ELEGANS DROSOPHILA ZEBRAFISH, MOUSE DOG, CAT MAN, GIANT TORTOISE RANGE < 1 DAY WEEK – MONTH MONTH – YEAR YEAR – DECADE DECADE CENTURY

17 agedent.ppt17 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 ?

18 agedent.ppt18 TEAR AND WEAR OR PROGRAMME ? AGING IS NOT LIKELY TO BE REGULATED IN THE SAME PROGRAMMED WAY AS DEVELOPMENT Kirkwood, 1982, 1996

19 agedent.ppt19 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

20 agedent.ppt20 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

21 agedent.ppt21 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

22 agedent.ppt22 EVOLUTION OF AGEING UNICELLULAR 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)

23 agedent.ppt23 REPLICATIVE AGEING

24 agedent.ppt24 EVOLUTION OF AGEING Caenorhabditis elegans (simple multicellular) _age1 – prolonging of MLSP by 110 % Resistance against oxidants, increased temperature, UV rays Activity of SOD and catalase _Daf 2,23,28 mutations _Genes of signal transduction ! STRESS RESPONSE GENES _spe26 (gamete production), clk1 (internal rytmus)

25 agedent.ppt25 EVOLUTION OF AGEING Drosophila melanogaster _Different lines with prolonged life span Resistance against oxidants Resistance against starvation and dehydratation But also flies in small boxes and without wings (?) _Transgenic drosophila +SOD = 0; +CAT = 0; +(SOD & CAT) = 30%

26 agedent.ppt26 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

27 agedent.ppt27 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

28 agedent.ppt28 THE OLDEST OLD SELECTIVE SURVIVAL ? Mortality over 90 – turn on the curve men > women Incidence of Alzheimer disease Short period before death Which genes? APO E ?, ACE ?

29 agedent.ppt29 THE OLDEST OLD aTIZIANO V1477 - 157698 – PIETA aVERDI G 1813 - 190280 – FALSTAFF aPICASSO P 1881 - 197386 – LE COUPLE aCHURCHILL, CASALS, KŇAZOVICKÝ... aQUEEN MOTHER, MOJSEJEV (102) aJOHN GLENN, 1922 (1962, 1999 and his 96 years old friend)

30 agedent.ppt30 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


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