Evolution, mutations, and human longevity: European royal and noble families

Area of Science:

• Evolutionary biology
• Gerontology
• Quantitative genetics

Background:

• The evolutionary theory of aging posits that deleterious mutations accumulate with age due to relaxed selection.
• This mutation accumulation hypothesis predicts increased genetic variance for survival as organisms age.
• Heritability of longevity, estimated via offspring-on-parental age regression, is a key metric.

Purpose of the Study:

• To test the evolutionary theory of aging's prediction regarding age-specific selection on mutations.
• To investigate if heritability of longevity increases with advancing paternal age.
• To validate the mutation accumulation hypothesis using empirical data.

Main Methods:

• Analysis of extensive genealogical data from European royal and noble families.
• Multiple regression modeling of offspring longevity (n=12,150) against paternal age at death, reproduction, and cohort life expectancy.
• Estimation of heritability of life span as the doubled slope of offspring lifespan on paternal age at death.

Main Results:

• The regression slope of offspring longevity on paternal longevity significantly increased with paternal longevity.
• This finding supports the prediction that selection against late-acting deleterious mutations weakens with age.
• Heritability of longevity was found to increase with paternal age at reproduction.

Conclusions:

• The study provides empirical support for the evolutionary theory of aging and the mutation accumulation hypothesis.
• Longevity is influenced by late-acting deleterious mutations, with their effects becoming more pronounced with age.
• Genetic factors contributing to survival and longevity are age-dependent.