Multiple Metazoan Life-span Interventions Exhibit a Sex-specific Strehler-Mildvan Inverse Relationship Between Initial Mortality Rate and Age-dependent Mortality Rate Acceleration

摘要

The Gompertz equation describes survival in terms of initial mortality rate (parameter a), indicative of health, and age-dependent acceleration in mortality rate (parameter b), indicative of aging. Gompertz parameters were analyzed for several published studies. In Drosophila females, mating increases egg production and decreases median life span, consistent with a trade-off between reproduction and longevity. Mating increased parameter a, causing decreased median life span, whereas time parameter b was decreased. The inverse correlation between parameters indicates the Strehler-Mildvan (S-M) relationship, where loss of low-vitality individuals yields a cohort with slower age-dependent mortality acceleration. The steroid hormone antagonist mifepristone/RU486 reversed these effects. Mating and mifepristone showed robust S-M relationships across genotypes, and dietary restriction showed robust S-M relationship across diets. Because nutrient optima differed between females and males, the same manipulation caused opposite effects on mortality rates in females versus males across a range of nutrient concentrations. Similarly, p53 mutation in Drosophila and mTOR mutation in mice caused increased median life span associated with opposite direction changes in mortality rate parameters in females versus males. The data demonstrate that dietary and genetic interventions have sex-specific and sometimes sexually opposite effects on mortality rates consistent with sexual antagonistic pleiotropy.