1 / 55

Testing Evolutionary Theory on Longevity and Fertility with Demographic and Genealogical Data

This study examines the data and predictions of evolutionary theory on the links between human longevity and fertility, lifespan heritability, and quality of offspring conceived by older parents.

idellaj
Download Presentation

Testing Evolutionary Theory on Longevity and Fertility with Demographic and Genealogical Data

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Testing Biological Ideas on Evolution, Aging and Longevity with Demographic and Genealogical Data Natalia S. Gavrilova Leonid A. Gavrilov Center on Aging, NORC/University of Chicago, 1155 East 60th Street, Chicago, IL 60637

  2. What are the data and the predictions of the evolutionary theory on • Links between human longevity and fertility • Lifespan heritability in humans • Quality of offspring conceived to older parents

  3. Founding Fathers • Beeton, M., Yule, G.U., Pearson, K. 1900. Data for the problem of evolution in man. V. On the correlation between duration of life and the number of offspring. Proc. R. Soc. London, 67: 159-179. • Data used: English Quaker records and Whitney Family of Connectucut records for females and American Whitney family and Burke’s ‘Landed Gentry’ for males.

  4. Findings and Conclusions by Beeton et al., 1900 • They tested predictions of the Darwinian evolutionary theory that the fittest individuals should leave more offspring. • Findings: Slightly positive relationship between postreproductive lifespan (50+) of both mothers and fathers and the number of offspring. • Conclusion: “fertility is correlated with longevity even after the fecund period is passed” and “selective mortality reduces the numbers of the offspring of the less fit relatively to the fitter.”

  5. Other Studies, Which Found Positive Correlation Between Reproduction and Postreproductive Longevity Telephone inventor Alexander Graham Bell (1918): “The longer lived parents were the most fertile.” • Bettie Freeman (1935): Weak positive correlations between the duration of postreproductive life in women and the number of offspring borne. Human Biology, 7: 392-418. • Bideau A. (1986): Duration of life in women after age 45 was longer for those women who borne 12 or more children. Population 41: 59-72.

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

  7. Study that Found a Trade-OffBetween Reproductive Success and Postreproductive Longevity • Westendorp RGJ, Kirkwood TBL. 1998. Human longevity at the cost of reproductive success. Nature 396: 743-746. • Extensive media coverage including BBC and over 100 citations in scientific literature as an established scientific fact. Previous studies were not quoted and discussed in this article.

  8. Point estimates of progeny number for married aristocratic women from different birth cohorts as a function of age at death.The estimates of progeny number are adjusted for trends over calendar time using multiple regression. Source: Westendorp, Kirkwood, Human longevity at the cost of reproductive success. Nature, 1998, 396, pp 743-746

  9. Number of progeny and age at first childbirth dependent on the age at death of married aristocratic women Source: Westendorp, R. G. J., Kirkwood, T. B. L. Human longevity at the cost of reproductive success. Nature, 1998, 396, pp 743-746

  10. “… it is not a matter of reduced fertility, but a case of 'to have or have not'.“ Source: Toon Ligtenberg & Henk Brand. Longevity — does family size matter? Nature, 1998, 396, pp 743-746

  11. Source: Westendorp, R. G. J., Kirkwood, T. B. L. Human longevity at the cost of reproductive success. Nature, 1998, 396, pp 743-746

  12. Do longevous women have impaired fertility ?Why is this question so important and interesting?Scientific Significance This is a testable prediction of some evolutionary theories of aging - disposable soma theory of aging (Kirkwood) "The disposable soma theory on the evolution of ageing states that longevity requires investments in somatic maintenance that reduce the resources available for reproduction“ (Westendorp, Kirkwood, Nature, 1998).

  13. Do longevous women have impaired fertility ? • Practical Importance. Do we really wish to live a long life at the cost of infertility?: “the next generations of Homo sapiens will have even longer life spans but at the cost of impaired fertility” Rudi Westendorp “Are we becoming less disposable? EMBO Reports, 2004, 5: 2-6. "... increasing longevity through genetic manipulation of the mechanisms of aging raises deep biological and moral questions. These questions should give us pause before we embark on the enterprise of extending our lives“ Walter Glennon "Extending the Human Life Span", Journal of Medicine and Philosophy, 2002, Vol. 27, No. 3, pp. 339-354.

  14. Educational Significance • Do we teach our students right? Impaired fertility of longevous women is often presented in scientific literature and mass media as already established fact (Brandt et al., 2005; Fessler et al., 2005; Schrempf et al., 2005; Tavecchia et al., 2005; Kirkwood, 2002; Westendorp, 2002, 2004; Glennon, 2002; Perls et al., 2002, etc.). This "fact" is now included in teaching curriculums in biology, ecology and anthropology world-wide (USA, UK, Denmark). • Is it a fact or artifact ?

  15. General Methodological Principle: • Before making strong conclusions, consider all other possible explanations, including potential flaws in data quality and analysis • Previous analysis by Westendorp and Kirkwood was made on the assumption of data completeness:Number of children born = Number of children recorded • Potential concerns: data incompleteness, under-reporting of short-lived children, women (because of patrilineal structure of genealogical records), persons who did not marry or did not have children.Number of children born   >> Number of children recorded

  16. Test for Data Completeness Direct Test: Cross-checking of the initial dataset with other data sources We examined 335 claims of childlessness in the dataset used by Westendorp and Kirkwood. When we cross-checked these claims with other professional sources of data, we  found that at least 107 allegedly childless women (32%) did have children! At least 32% of childlessness claims proved to be wrong ("false negative claims") ! Some illustrative examples: Henrietta Kerr (1653­1741) was apparently childless in the dataset used by Westendorp and Kirkwood and lived 88 years. Our cross-checking revealed that she did have at least one child, Sir William Scott (2nd Baronet of Thirlstane, died on October 8, 1725). Charlotte Primrose (1776­1864) was also considered childless in the initial dataset and lived 88 years. Our cross-checking of the data revealed that in fact she had as many as five children: Charlotte (1803­1886), Henry (1806­1889), Charles (1807­1882), Arabella (1809-1884), and William (1815­1881). Wilhelmina Louisevon Anhalt-Bernburg (1799­1882), apparently childless, lived 83 years. In reality, however, she had at least two children, Alexander (1820­1896) and Georg (1826­1902).

  17. Point estimates of progeny number for married aristocratic women from different birth cohorts as a function of age at death.The estimates of progeny number are adjusted for trends over calendar time using multiple regression. Source: Westendorp, R. G. J., Kirkwood, T. B. L. Human longevity at the cost of reproductive success. Nature, 1998, 396, pp 743-746

  18. Antoinette de Bourbon(1493-1583) Lived almost 90 years She was claimed to have only one child in the dataset used by Westendorp and Kirkwood: Marie (1515-1560), who became a mother of famous Queen of Scotland, Mary Stuart. Our data cross-checking revealed that in fact Antoinette had 12 children! • Marie 1515-1560 • Francois Ier 1519-1563 • Louise 1521-1542 • Renee 1522-1602 • Charles 1524-1574 • Claude 1526-1573 • Louis 1527-1579 • Philippe 1529-1529 • Pierre 1529 • Antoinette 1531-1561 • Francois 1534-1563 • Rene 1536-1566

  19. Characteristics of Our Data Sample for ‘Reproduction-Longevity’ Studies • 3,723 married women born in 1500-1875 and belonging to the upper European nobility. • Women with two or more marriages (5%) were excluded from the analysis in order to facilitate the interpretation of results (continuity of exposure to childbearing). • Every case of childlessness has been checked using at least two different genealogical sources.

  20. Typical Mistakes in Biological Studies of Human Longevity • Using lifespan data for non-extinct birth cohorts (“cemetery effect”) • Failure to control for birth cohort – spurious correlations may be found if variables have temporal dynamics • Failure to take into account social events and factors – e.g., failure to control for age at marriage in longevity-reproduction studies

  21. Childlessness is better outcome than number of children for testing evolutionary theories of aging on human data • Applicable even for population practicing birth control (few couple are voluntarily childless) • Lifespan is not affected by physiological load of multiple pregnancies • Lifespan is not affected by economic hardship experienced by large families

  22. Source: Gavrilova et al. Does exceptional human longevity come with high cost of infertility? Testing the evolutionary theories of aging. Annals of the New York Academy of Sciences, 2004, 1019: 513-517.

  23. Source: Gavrilova, Gavrilov. Human longevity and reproduction: An evolutionary perspective. In: Grandmotherhood - The Evolutionary Significance of the Second Half of Female Life. Rutgers University Press, 2005, 59-80.

  24. Short Conclusion: Exceptional human longevity is NOT associated with infertility or childlessness

  25. More Detailed Conclusions • We have found that previously reported high rate of childlessness among long-lived women is an artifact of data incompleteness, caused by under-reporting of children. After data cleaning, cross-checking and supplementation the association between exceptional longevity and childlessness has disappeared. • Thus, it is important now to revise a highly publicized scientific concept of heavy reproductive costs for human longevity. and to make corrections in related teaching curriculums for students.

  26. More Detailed Conclusions (2) • It is also important to disavow the doubts and concerns over further extension of human lifespan, that were recently cast in biomedical ethics because of gullible acceptance of the idea of harmful side effects of lifespan extension, including infertility (Glannon, 2002). • There is little doubt that the number of children can affect human longevity through complications of pregnancies and childbearing, as well as through changes in socioeconomic status,  etc.  However,  the concept of heavy infertility cost of human longevity is not supported by data, when these data are carefully reanalyzed.

  27. Mutation Accumulation Theory of Aging (Medawar, 1946) • From the evolutionary perspective, aging is an inevitable result of the declining force of natural selection with age. • So, over successive generations, late-acting deleterious mutations will accumulate, leading to an increase in mortality rates late in life.

  28. Predictions of the Mutation Accumulation Theory of Aging • Mutation accumulation theory predicts that those deleterious mutations that are expressed in later life should have higher frequencies (because mutation-selection balance is shifted to higher equilibrium frequencies due to smaller selection pressure). • Therefore, ‘expressed’ genetic variability should increase with age (Charlesworth, 1994. Evolution in Age-structured Populations). • This should result in higher heritability estimates for lifespan of offspring born to longer-lived parents.

  29. Linearity Principle of Inheritance in Quantitative Genetics • Dependence between parental traits and offspring traits is linear

  30. The Best Possible Source on Familial Longevity Genealogies of European Royal and Noble Families Marie-Antoinette von Habsburg-Lothringen (1765-1793) Charles IX d’Anguleme (1550-1574) Henry VIII Tudor (1491-1547)

  31. Characteristic of our Dataset • Over 16,000 persons belonging to the European aristocracy • 1800-1880 extinct birth cohorts • Adult persons aged 30+ • Data extracted from the professional genealogical data sources including Genealogisches Handbook des Adels, Almanac de Gotha, Burke Peerage and Baronetage.

  32. Daughter's Lifespan(Mean Deviation from Cohort Life Expectancy)as a Function of Paternal Lifespan • Offspring data for adult lifespan (30+ years) are smoothed by 5-year running average. • Extinct birth cohorts (born in 1800-1880) • European aristocratic families. 6,443 cases

  33. “The Heritability of Life-Spans Is Small”C.E. Finch, R.E. Tanzi, Science, 1997, p.407 Paradox of low heritability of lifespan vs high familial clustering of longevity “… long life runs in families” A. Cournil, T.B.L. Kirkwood, Trends in Genetics, 2001, p.233

  34. Heritability Estimates of Human Lifespan

  35. Is the effect of non-linear inheritance remain valid after controlling for other explanatory variables? Lifespan of other parent Parental ages at child’s conception Ethnicity Month of birth

  36. Offspring Lifespan at Age 30 as a Function of Paternal LifespanData are adjusted for other predictor variables Daughters, 8,284 cases Sons, 8,322 cases

  37. Offspring Lifespan at Age 30 as a Function of Maternal LifespanData are adjusted for other predictor variables Daughters, 8,284 cases Sons, 8,322 cases

  38. Is the effect of non-linear inheritance observed for non-biological relatives? We need to test an alternative hypothesis that positive effects of long-lived parents on the offspring survival may be non-biological and caused by common environment and life style What about lifespan of spouses?

  39. Person’s Lifespan as a Function of Spouse LifespanData are adjusted for other predictor variables Married Women, 4,530 cases Married Men, 5,102 cases

  40. What about lifespan of other relatives? (sisters vs sisters-in-law)

  41. Person’s Lifespan as a Function of Sisters LifespanData are adjusted for other predictor variables Females, 5,421 cases Males, 7,378 cases

  42. Person’s Lifespan as a Function of Sisters-In-Law LifespanData are adjusted for other predictor variables Females, 4,789 cases Males, 4,707 cases

  43. Mortality Kinetics for Progeny Born to Long-Lived (80+) vs Short-Lived ParentsData are adjusted for historical changes in lifespan Sons Daughters

  44. Parental-Age Effects in Humans(accumulation of mutation load in parental germ cells) What are the Data and the Predictions of Evolutionary Theory on the Quality of Offspring Conceived to Older Parents? Does progeny conceived to older parents live shorter lives?

  45. Evolutionary Justification for Parental-Age Effects • "The evolutionary explanation of senescence proposes that selection against alleles with deleterious effects manifested only late in life is weak because most individuals die earlier for extrinsic reasons. • This argument also applies to alleles whose deleterious effects are nongenetically transmitted from mother to progeny, that is, that affect the performance of progeny produced at late ages rather than of the aging individuals themselves. • … a decline of offspring quality with parental age should receive more attention in the context of the evolution of aging.” Stearns et al. "Decline in offspring viability as a manifestation of aging in Drosophila melianogaster." Evolution, 2001, Vol. 55, No. 9, pp. 1822–1831.

  46. Genetic Justification for Paternal Age Effects • Advanced paternal age at child conception is the main source of new mutations in human populations. James F. Crow, geneticist Professor Crow (University of Wisconsin-Madison) is recognized as a leader and statesman of science. He is a member of the National Academy of Sciences, the National Academy of Medicine, The American Philosophical Society, the American Academy of Arts and Sciences, the World Academy of Art and Science.

  47. Paternal Age and Risk of Schizophrenia • Estimated cumulative incidence and percentage of offspring estimated to have an onset of schizophrenia by age 34 years, for categories of paternal age. The numbers above the bars show the proportion of offspring who were estimated to have an onset of schizophrenia by 34 years of age. • Source: Malaspina et al., Arch Gen Psychiatry.2001.

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

  49. Daughters' Lifespan (30+) as a Functionof Paternal Age at Daughter's Birth6,032 daughters from European aristocratic families born in 1800-1880 • Life expectancy of adult women (30+) as a function of father's age when these women were born (expressed as a difference from the reference level for those born to fathers of 40-44 years). • The data are point estimates (with standard errors) of the differential intercept coefficients adjusted for other explanatory variables using multiple regression with nominal variables. • Daughters of parents who survived to 50 years.

More Related