Biodemography of Human Longevity: New Findings and Ideas

1. Biodemography of Human Longevity: New Findings and Ideas Dr. Leonid A. Gavrilov, Ph.D. Dr. Natalia S. Gavrilova, Ph.D. Center on Aging NORC and The University of Chicago Chicago, Illinois, USA

2. Approach To study “success stories” in long-term avoidance of fatal diseases (survival to 100 years) and factors correlated with this remarkable survival success

3. Centenarians represent the fastest growing age group in the industrialized countries Yet, factors predicting exceptional longevity and its time trends remain to be fully understood In this study we explored the new opportunities provided by the ongoing revolution in information technology, computer science and Internet expansion to explore early-childhood predictors of exceptional longevity Jeanne Calment (1875-1997)

4. Revolution in Information TechnologyWhat does it mean for longevity studies? Over 75 millions of computerized genealogical records are available onlinenow!

5. Computerized genealogies is a promising source of information about potential predictors of exceptional longevity: life-course events, early-life conditions and family history of longevity

6. Computerized Genealogies as a Resource for Longevity Studies • Pros: provide important information about family and life-course events, which otherwise is difficult to collect (including information about lifespan of parents and other relatives) • Cons: Uncertain data quality Uncertain validity and generalizability

7. For longevity studies the genealogies with detailed birth dates and death dates for long-lived individuals (centenarians) and their relatives are of particular interest In this study 1,001 genealogy records for centenarians born in 1875-1899 were collected and used for further age validation

9. Steps of Centenarian Age Verification • Internal consistency checks of dates • Verification of death dates – linkage to the Social Security Administration Death Master File (DMF) • Verification of birth dates – linkage to early Federal censuses (1900, 1910, 1920, 1930)

10. Results of Centenarian Age Verification

11. Conclusions of the Age Verification Study • Death dates of centenarians recorded in genealogies always require verification because of strong outliers (1.3%, misprints) • Birth dates of centenarians recorded in genealogies are sufficiently accurate - 92% are correct; for the remaining 8% only one-year disagreements • Quality of genealogical data is good enough if these data are pre-selected for high data quality

12. Predictors of Exceptional Longevity

13. Within-Family Study of Exceptional Longevity Cases - 198 Centenarians born in U.S. in 1890-1893 Controls – Their own siblings Method: Conditional logistic regression Advantage: Allows researchers to eliminate confounding effects of between-family variation

14. Design of the Study

15. A typical image of ‘centenarian’ family in 1900 census

16. First-born siblings are more likely to become centenarians (odds = 1.8)

17. Birth Order and Odds to Become a Centenarian

18. Can the birth-order effect be a result of selective child mortality, thus not applicable to adults? Approach: • To compare centenarians with those siblings only who survived to adulthood (age 20)

19. First-born adult siblings (20+years) are more likely to become centenarians (odds = 1.95)

20. Are young fathers responsible for birth order effect?

21. Birth order is more important than paternal age for chances to become a centenarian

22. Are young mothers responsible for the birth order effect?

23. Maternal Age at Person’s Birth and Odds to Become a Centenarian

24. Birth order effect explained:Being born to young mother!

25. Even at age 75 it still helps to be born to young mother (age <25)(odds = 1.9)

26. Question • Families were quite large in the past, particularly those covered by genealogical records (large family size bias). • Is the "young mother effect" robust to the family size, and is it observed in smaller families too? • Or is it confined to extremely large families only? Approach: To split data in two equal parts by median family size (9 children) and re-analyze the data in each group separately.

27. Results • In smaller families (less than 9 children) the effect of young mother is even larger: Odds ratio = 2.23, P=0.004; 95%CI = 1.30 - 3.98 • Compare to larger families (more than 9 children): Odds ratio = 1.72, P=0.11; 95%CI = 0.88 - 3.34 Conclusion: "Young mother effect" is not confined to extremely large family size

28. New Striking Findings: Invitation for discussion and brain-storming! The favorable "Young Mother Effect" is particularly strong when parents have particularly large differences in their lifespan

29. Odds Ratio to live to 100 years if born to young motheras a function of maternal and paternal lifespans (tertiles) * p<0.05

30. Being born to Young Mother Helps Laboratory Mice to Live Longer • Source: Tarin et al., Delayed Motherhood Decreases Life Expectancy of Mouse Offspring. Biology of Reproduction 2005 72: 1336-1343.

31. Physical Characteristics at Young Age and Survival to 100 A study of height and build of centenarians when they were young using WWI civil draft registration cards

32. Height – What to Expect Height seems to be a good indicator of nutritional status and infectious disease history in the past. Historical studies showed a negative correlation between height and mortality. Hence we may expect that centenarians were taller than average

33. Build – What to Expect Slender build may suggest a poor nutrition during childhood. We may expect that centenarians were less likely to be slender when young. On the other hand, biological studies suggest that rapid growth may be harmful and somewhat delayed maturation may be beneficial for longevity.

34. Data Sources Social Security Administration Death Master File WWI civil draft registration cards (completed for almost 100 percent men born between 1873 and 1900)

35. Study Design Cases: men centenarians born in 1887 (randomly selected from the SSA Death Master File) and linked to the WWI civil draft records. Out of 120 selected men, 19 were not eligible for draft. The linkage success for remaining 101 records was 75% (76 records) Controls: men matched on birth year, race and county of WWI civil draft registration

36. Height and Survival to 100

37. Body Build and Survival to 100

38. Results of multivariate study

39. Conclusion The study of height and build among men born in 1887 suggests that rapid growth and overweight at young adult age (30 years) might be harmful for attaining longevity

40. What are the Links Between Human Longevity and Fertility? Testing the evolutionary theory of aging

41. 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.

42. 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.”

43. Other Studies, Which Found Positive Correlation Between Reproduction and Postreproductive Longevity • 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. Telephone inventor Alexander Graham Bell (1918): “The longer lived parents were the most fertile.”

44. 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.

45. 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.

46. 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

47. “… 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

48. 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

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

50. 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).