Exceptional Parental Longevity and Onset of Morbidity and Mortality Across Cohorts

Centenarian lifespan extension is frequently accompanied by delayed onset of aging-associated diseases. Understanding the transgenerational patterns of this phenomenon is crucial for informing investigations of genetic and environmental factors that promote healthy aging.

To evaluate the extent and consistency with which centenarians' offspring exhibit delayed onset of death and age-associated morbidities as well as decreased risk of age-related morbidities across independent cohorts.

Three independent longitudinal cohorts were studied: LonGenity (2008-2024; New York City area), the New England Centenarian Study (NECS; 1995-2024; throughout the US), and the UK Biobank (2006-2022; throughout the UK). Participants were selected from the 3 studies based on their parental lifespan. Data were analyzed between July 2024 and June 2026.

Centenarians' offspring had at least 1 parent who reached age 100 years and were compared with control offspring of parents with shorter lifespans.

Differences in age at death and age at onset of 4 age-associated morbidities-cardiovascular disease (CVD), cancer, hypertension, and stroke-were evaluated within study cohorts using Cox proportional hazards regression modeling, estimating hazard ratios (HRs) and delays in expected age of incidence.

Combined, centenarians' offspring and control participants numbered 480 in LonGenity (median enrollment age, 74 years [range, 65-94 years]; 262 women [55%]; 245 offspring of centenarians [51%]), 1566 in NECS (median enrollment age, 71 years [range, 39-100 years]; 923 women [59%]; 1082 offspring of centenarians [69%]), and 1984 in the UK Biobank (median enrollment age, 65 years [range, 42-71 years]; 1006 women [51%]; 992 offspring of centenarians [50%]). Meta-analyses identified consistently reduced hazards for death, CVD, and hypertension, with aggregate HR estimates of 0.58 (95% CI, 0.41-0.81) for death, 0.67 (95% CI, 0.46-0.97) for CVD, and 0.68 (95% CI, 0.62-0.75) for hypertension, and delays of 3.12 years (95% CI, 0.96-5.28 years) for death and 5.21 years (95% CI, 2.13-8.29 years) for hypertension. Stroke hazards were reduced only in LonGenity (HR, 0.27 [95% CI, 0.09-0.81]) and NECS (HR, 0.41 [95% CI, 0.27-0.63]). No significant associations with cancer were identified.

In this cohort study of parental longevity, centenarians' offspring exhibited delayed onset of mortality and several morbidities as well as reduced age-associated risk for several morbidities. These findings support the value of using this group as a research model for identifying factors that may promote healthy aging and the suitability of parental longevity as a criterion in prospective studies of resilience.