Measures of health in old age and measures of mortality and longevity should all stem from the same root causes: the state of cellular damage, the integrity of repair systems, decline in function of organs, and so on. So if one of these general measures is shown to be inherited to a given degree, you'd expect the rest to be similarly heritable.
Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI's association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study.
The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model.
Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well and slightly worse than age alone. Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities. In Long Life Family Study, the heritability of the HAI was 0.295 overall, 0.387 in probands, and 0.238 in offspring.