Protective Effects of Familial Longevity on Age-Specific Mortality Disappear at Older Ages

1. Protective Effects of Familial Longevity on Age-Specific Mortality Disappear at Older Ages Leonid A. Gavrilov, Ph.D. Natalia S. Gavrilova, Ph.D. Center on Aging NORC and The University of Chicago Chicago, Illinois, USA

2. Prediction of the Mutation Accumulation Theory of Aging (Medawar, 1946) • The theory predicts that the observed pattern of familial transmission of human lifespan is caused by higher equilibrium frequency of late-acting deleterious mutations at older ages (Medawar 1952). • Therefore, children born to long-lived parents should experience survival advantage mostly in their old ages (because they have less late-acting deleterious mutations).

3. Alternative hypotheses • Reliability theory of aging predicts that children born to long living parents will experience survival advantage mostly in their younger adult ages, because of higher redundancy in functional elements (cells) not yet exhausted over time (Gavrilov and Gavrilova 2006). • The third hypothesis suggests the life-long sustained mortality advantage for persons having protection of familial longevity (Perls et al. 2002).

4. Description of Dataset on European Aristocracy • 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.

5. Risk of death increases exponentially with age. The Gompertz Law μ(x) = R e αx R – intercept coefficient (in semi-log scale) α – slope coefficient (in semi-log scale) x - age

6. Parental Longevity Effects (European Aristocracy) Mortality Kinetics for Progeny Born to Long-Lived (80+) vs Short-Lived Parents 1 1 2 1 1 2 2 2 Sons Daughters

7. Effect of parental longevity on the Gompertz parameters for daughters European Aristocracy

8. Effect of parental longevity on the Gompertz parameters for sons European Aristocracy

9. American centenarians born in 1890-1897

10. Database on Exceptional Longevity • About 4,000 records of centenarians born in the United States. Age of centenarians was validated using the Social Security Death Master File linkage (82% validated) • About 4,000 records of shorter-lived controls (died at age 65 years) • Both centenarians and controls have information about lifespan of parents • Both centenarians and controls have information about siblings, children, souses, siblings-in-law and grandparents

11. Data used in the study

12. Parental longevity does not affect survival after age 100

13. Survival of siblings with different levels of familial longevity I - siblings of shorter-lived persons (died at age 65) II - siblings of centenarians

14. Mortality of men with different levels of familial longevity Short-lived Long-lived

15. Mortality of women with different levels of familial longevity Short-lived Long-lived

16. Parameters of the Gompertz model for siblings of long-lived and short-lived individuals Slope coefficients indicate mortality convergence at older ages.

17. Conclusions • Familial longevity improves survival mostly at younger adult rather than older ages • Parental longevity has no significant effect on survival of centenarians • These findings support predictions of reliability theory of aging, but do not support predictions of the mutation accumulation theory of aging, as well as the hypothesis of life-long sustained mortality advantage.

18. Acknowledgments This study was made possible thanks to: generous support from the National Institute on Aging and the Society of Actuaries

19. For More Information and Updates Please Visit Our Scientific and Educational Website on Human Longevity: • http://longevity-science.org And Please Post Your Comments at our Scientific Discussion Blog: • http://longevity-science.blogspot.com/

20. Survival of Centenarians F M