1. NORC and The University of Chicago
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
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. μ(x) = R e αx The Gompertz Law
Risk of death increases exponentially with age.
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
Offspring group
Intercept [95% CI]
Slope [95% CI]
Both parents long lived (80+), N=323
-11.08
[-11.80, ]
0.107
[0.098, 0.116]
Long-lived mother, N=1,390
-9.93
[-10.22, -9.65]
0.093
[0.090, 0.097]
Long-lived father, N=940
-10.17
[-10.53, -9.80]
0.097
[0.092, 0.102]
Both parents short-lived, N=4,854
-9.60
[-9.74, -9.45]
0.091
[0.089, 0.093]
European Aristocracy

8. Effect of parental longevity on the Gompertz parameters for sons
Offspring group
Intercept [95% CI]
Slope [95% CI]
Both parents long lived (80+), N=285
-9.21
[-9.79, -8.62]
0.089
[0.081, ]
Long-lived mother, N=1,401
-8.81
[-9.05, -8.57]
0.086
[0.082, 0.089]
Long-lived father, N=1,026
-8.95
[-9.24, ]
[0.082, ]
Both parents short-lived, N=4,736
-8.49
[-8.61, -8.37]
0.083
[0.081, 0.085]
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. Identified relatives of cases
Data used in the study
Shorter-lived persons (65 years)
Longer-lived persons (100+)
Men
Women
Identified cases
1648
1760
Identified relatives of cases
Parents
3296
3520
Siblings
2183
1895
2018
1646

12. Parental longevity does not affect survival after age 100
Variable
Hazard Ratio
95% CI
P-value
Paternal lifespan 80+
0.976
0.912, 1.045
0.486
Maternal lifespan 80+
0.944
0.883, 1.010
0.094
Sex (0- men, 1-women)
0.854
0.799, 0.914
<0.001
Second analysis:
Paternal lifespan 90+
0.999
0.897, 1.112
0.981
Maternal lifespan 90+
0.980
0.894, 1.074
0.855
0.800, 0.915

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. Slope coefficients indicate mortality convergence at older ages.
Parameters of the Gompertz model for siblings of long-lived and short-lived individuals
Group
Slope coefficient (95% CI)
Intercept coefficient (95% CI)
Men
Siblings of long-lived
0.092 (0.088,0.096)
( , )
Siblings of short-lived
0.081 (0.077,0.084)
( , )
Women
0.095 (0.091,0.099)
( , )
0.083 (0.079,0.086)
( , )
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. This study was made possible thanks to:
Acknowledgments
This study was made possible thanks to:
generous support from the National Institute on Aging and the Society of Actuaries

19. And Please Post Your Comments at our Scientific Discussion Blog:
For More Information and Updates Please Visit Our Scientific and Educational Website on Human Longevity:
And Please Post Your Comments at our Scientific Discussion Blog:

20. Survival of CentenariansM