Hereditary qualities of Human Longevity: New Ideas and Findings

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Hereditary qualities of Human Longevity: New Ideas and Findings Dr. Natalia S. Gavrilova, Ph.D. Focus on Aging, NORC and the University of Chicago, Chicago, Illinois, USA

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Three logical issues: Mechanisms of familial transmission of human life span Paradox of low heritability of life expectancy versus high familial grouping of life span Parental-age impacts (aggregation of transformation load in parental germ cells) Does offspring imagined to more established guardians live shorter lives? Does outstanding human life span accompany high cost of barrenness? Testing the transformative hypotheses of maturing

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"The Heritability of Life-Spans Is Small" C.E. Finch, R.E. Tanzi, Science , 1997, p.407 Paradox of low heritability of life expectancy versus high familial grouping of life span "… long life keeps running in families" A. Cournil, T.B.L. Kirkwood, Trends in Genetics , 2001, p.233

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Heritability Estimates of Human Lifespan

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Early Study on Familial Longevity This study found that the relatives of nonagenarians and centenarians live longer than relatives of shorter-lived people These discoveries were affirmed in later studies (Gudmundsson et al., 2000; Perls et al., 2002 and others )

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Characteristic of our Dataset Over 16,000 people having a place with the European privileged 1800-1880 terminated birth companions Adult people matured 30+ Data separated from the expert genealogical information sources including Genealogisches Handbook des Adels, Almanac de Gotha, Burke Peerage and Baronetage.

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Daughter's Lifespan (Mean Deviation from Cohort Life Expectancy) as a Function of Paternal Lifespan Offspring information for grown-up life expectancy (30+ years) are smoothed by 5-year running normal. Terminated birth companions (conceived in 1800-1880) European blue-blooded families. 6,443 cases

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Unusual Non-straight Pattern of Lifespan Inheritance It is hypothetically anticipated (by quantitative hereditary qualities) and tentatively affirmed that the reliance of most posterity quantitative characteristics (body weight for instance) on parental attributes is direct. Be that as it may, if a few guardians are harmed amid early advancement and in this manner have shorter life expectancy (in spite of having typical germ cell DNA), the reliance for life expectancy legacy ought to wind up non-direct. This is on the grounds that the posterity destined to these brief guardians with typical germ cell DNA ought to have ordinary instead of shorter life expectancy

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Offspring Lifespan at Age 30 as a Function of Paternal Lifespan Data are balanced for other indicator factors Daughters, 8,284 cases Sons, 8,322 cases

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Offspring Lifespan at Age 60 as a Function of Paternal Lifespan Data are balanced for other indicator factors Daughters, 6,517 cases Sons, 5,419 cases

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Offspring Lifespan at Age 30 as a Function of Maternal Lifespan Data are balanced for other indicator factors Daughters, 8,284 cases Sons, 8,322 cases

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Offspring Lifespan at Age 60 as a Function of Maternal Lifespan Data are balanced for other indicator factors Daughters, 6,517 cases Sons, 5,419 cases

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Person's Lifespan as a Function of Spouse Lifespan Data are balanced for other indicator factors Married Women, 4,530 cases Married Men, 5,102 cases

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Person's Lifespan as a Function of Sisters Lifespan Data are balanced for other indicator factors Females, 5,421 cases Males, 7,378 cases

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Person's Lifespan as a Function of Sisters-In-Law Lifespan Data are balanced for other indicator factors Females, 4,789 cases Males, 4,707 cases

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Mortality Kinetics Long-Lived Mutants of Mouse and Drosophila Mouse Snell overshadow mutant. Flurkey et al., PNAS, 2001. Drosophila mutant methuselah. Lin et al., Science, 1998.

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Mortality Kinetics for Progeny Born to Long-Lived (80+) versus Short-Lived Parents Data are balanced for authentic changes in life expectancy Sons Daughters

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Parental-Age Effects (amassing of transformation load in parental germ cells) Does descendants considered to more seasoned guardians live shorter lives?

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Daughters' Lifespan (30+) as a Function of Paternal Age at Daughter's Birth 6,032 little girls from European privileged families conceived in 1800-1880 Life anticipation of grown-up ladies (30+) as a component of father's age when these ladies were conceived (communicated as a distinction from the reference level for those destined to fathers of 40-44 years). The information are point gauges (with standard mistakes) of the differential catch coefficients balanced for other logical factors utilizing numerous relapse with ostensible factors. Girls of guardians who made due to 50 years.

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Paternal Age as a Risk Factor for Alzheimer Disease MGAD - real quality for Alzheimer Disease Source: L. Bertram et al. Neurogenetics, 1998, 1: 277-280.

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Paternal Age and Risk of Schizophrenia Estimated aggregate frequency and rate of posterity evaluated to have an onset of schizophrenia by age 34 years, for classes of fatherly age. The numbers over the bars demonstrate the extent of posterity who were evaluated to have an onset of schizophrenia by 34 years old. Source: Malaspina et al., Arch Gen Psychiatry. 2001.

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Is There Any Link Between Longevity and Fertility? What are the information and the expectations of the transformative hypothesis on this issue?

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Brief Historical Note Beeton, M., Yule, G.U., Pearson, K. 1900. Information for the issue of advancement in man. V. On the connection between's length of life and the quantity of posterity. Proc. R. Soc. London , 67: 159-179. Information utilized: English Quaker records and Whitney Family of Connectucut records for females and American Whitney family and Burke's 'Landed Gentry' for guys.

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Findings and Conclusions by Beeton et al., 1900 They tried forecasts of the Darwinian developmental hypothesis that the fittest people ought to leave all the more posterity. Discoveries: Slightly positive relationship between postreproductive life expectancy (50+) of both moms and fathers and the quantity of posterity. Conclusion: " fruitfulness is associated with life span even after the fertile period is passed " and " particular mortality diminishes the quantities of the posterity of the less fit moderately to the fitter. "

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Other Studies, Which Found Positive Correlation Between Reproduction and Postreproductive Longevity Alexander Graham Bell (1918): " The more drawn out lived guardians were the most fruitful ." Bettie Freeman (1935): Weak positive relationships between's the span of postreproductive life in ladies and the quantity of posterity borne. Human Biology , 7: 392-418. Bideau A. (1986): Duration of life in ladies after age 45 was longer for those ladies who borne at least 12 youngsters. Populace 41: 59-72.

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Studies that Found no Relationship Between Postreproductive Longevity and Reproduction Henry L. 1956. Travaux et Documents. Gauter, E. what's more, Henry L. 1958. Travaux et Documents , 26. Knodel, J. 1988. Demographic Behavior in the Past. Le Bourg et al., 1993. Trial Gerontology , 28: 217-232.

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Study that Found a Trade-Off Between Reproductive Success and Postreproductive Longevity Westendorp RGJ, Kirkwood TBL. 1998. Human life span at the cost of conceptive achievement. Nature 396: 743-746. Broad media scope including BBC and more than 70 references in logical writing as a set up logical actuality. Past studies were not cited and talked about in this article.

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Number of descendants and age at first labor subject to the age at death of wedded blue-blooded ladies Source: Westendorp, R. G. J., Kirkwood, T. B. L. Human life span at the cost of regenerative achievement. Nature, 1998, 396, pp 743-746

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Do longevous ladies have impeded ripeness ? Why is this question so vital and intriguing : Scientific Significance. This is a testable forecast of some transformative speculations of maturing (dispensable soma hypothesis of maturing, Westendorp, Kirkwood, 1998) Practical Importance. Do we truly wish to carry on with a long life at the cost of fruitlessness? Based these worries a proposal was made : "... expanding life span through hereditary control of the systems of maturing brings up profound organic and good issues. These inquiries ought to give us delay before we set out on the venture of expanding our lives" Walter Glennon "Extending the Human Life Span", Journal of Medicine and Philosophy , 2002, Vol. 27, No. 3, pp. 339-354 Educational Significance . Do we educate our understudies right? Debilitated ripeness of longevous ladies is regularly exhibited in logical writing and broad communications as officially settled actuality (Kirkwood, 2002; Westendorp, 2002; Glennon, 2002; Perls et al., 2002 and so forth.) Is it a reality or relic ?

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Point evaluations of descendants number for wedded refined ladies from various birth companions as a component of age at death. The evaluations of descendants number are balanced for patterns over date-book time utilizing numerous relapse . Source: Westendorp, R. G. J., Kirkwood, T. B. L. Human life span at the cost of conceptive achievement. Nature, 1998, 396, pp 743-746

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General Methodological Principle: Before making solid conclusions, consider all other conceivable clarifications, incorporating potential defects in information quality and investigation Previous examination by Westendorp and Kirkwood was made on the suspicion of information fulfillment: Number of kids conceived = Number of youngsters recorded Potential concerns: information deficiency, under-reporting of fleeting kids, ladies (due to patrilineal structure of genealogical records), people who did not wed or did not have kids. Number of kids conceived   >> Number of youngsters recorded

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Test for Data Completeness Direct Test: C

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