Exceptional Parental Longevity and Onset of Morbidity and Mortality Across Cohorts

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Importance: 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. Objectives: 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. Design, Setting, and Participants: 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. Exposure: Centenarians' offspring had at least 1 parent who reached age 100 years and were compared with control offspring of parents with shorter lifespans. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

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