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The National Institute on Aging Workshop on Uses of Survival Data in Research on Factors Affecting Aging Contributions from Dr. Leonid A. Gavrilov, Ph.D. Dr. Natalia S. Gavrilova, Ph.D. Center on Aging, NORC and the University of Chicago, Chicago, Illinois, USA

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The National Institute on Aging Workshop on Uses of Survival Data in Research on Factors Affecting Aging Contributions from

Dr. Leonid A. Gavrilov, Ph.D.

Dr. Natalia S. Gavrilova, Ph.D.

Center on Aging,

NORC and the University of Chicago,

Chicago, Illinois, USA

the heritability of life spans is small c e finch r e tanzi science 1997 p 407
“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

daughter s lifespan mean deviation from cohort life expectancy as a function of paternal lifespan
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
unusual non linear pattern of lifespan inheritance

Unusual Non-linear Pattern of Lifespan Inheritance

It is theoretically predicted (by quantitative genetics) and experimentally confirmed that the dependence of most offspring quantitative traits (body weight for example) on parental traits is linear.

However, if some parents are damaged during early development and therefore have shorter lifespan (despite having normal germ cell DNA), the dependence for lifespan inheritance should become non-linear.

This is because the offspring born to these short-lived parents with normal germ cell DNA should have normal rather than shorter lifespan

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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

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Offspring Lifespan at Age 60 as a Function of Paternal LifespanData are adjusted for other predictor variables

Daughters, 6,517 cases

Sons, 5,419 cases

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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

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Offspring Lifespan at Age 60 as a Function of Maternal LifespanData are adjusted for other predictor variables

Daughters, 6,517 cases

Sons, 5,419 cases

person s lifespan as a function of spouse lifespan data are adjusted for other predictor variables
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

mortality kinetics long lived mutants of mouse and drosophila
Mortality KineticsLong-Lived Mutants of Mouse and Drosophila

Mouse Snell dwarf 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+) vs Short-Lived ParentsData are adjusted for historical changes in lifespan

Sons

Daughters

parental age effects accumulation of mutation load in parental germ cells

Parental-Age Effects(accumulation of mutation load in parental germ cells)

Does progeny conceived to older parents live shorter lives?

paternal age and risk of schizophrenia
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.
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Contour plot for daughters’ lifespan (deviation from cohort mean) as a function of paternal lifespan (X axis) and paternal age at daughters’ birth (Y axis)

7984 cases

1800-1880 birth cohorts

European aristocratic families

Distance weighted least squares smooth

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Daughters’ Lifespan as a Function of Paternal Age at Daughters’ BirthData are adjusted for other predictor variables

Daughters of shorter-lived fathers (<80), 6727 cases

Daughters of longer-lived fathers (80+), 1349 cases

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For More Information and Updates Please Visit Our Scientific and Educational Website on Human Longevity:
  • http://longevity-science.org