Families Enriched for Exceptional Longevity also have Increased Health-Span: Findings from the Long Life Family Study

Abstract

Hypothesizing that members of families enriched for longevity delay morbidity compared to population controls and approximate the health-span of centenarians, we compared the health-spans of older generation subjects of the Long Life Family Study (LLFS) to controls without family history of longevity and to centenarians of the New England Centenarian Study (NECS) using Bayesian parametric survival analysis. We estimated hazard ratios, the ages at which specific percentiles of subjects had onsets of diseases, and the gain of years of disease-free survival in the different cohorts compared to referent controls. Compared to controls, LLFS subjects had lower hazards for cancer, cardiovascular disease, severe dementia, diabetes, hypertension, osteoporosis, and stroke. The age at which 20% of the LLFS siblings and probands had one or more age-related diseases was approximately 10 years later than NECS controls. While female NECS controls generally delayed the onset of age-related diseases compared with males controls, these gender differences became much less in the older generation of the LLFS and disappeared amongst the centenarians of the NECS. The analyses demonstrate extended health-span in the older subjects of the LLFS and suggest that this aging cohort provides an important resource to discover genetic and environmental factors that promote prolonged health-span in addition to longer life-span.

Keywords: Weibull regression; health-span; longevity; onset of disease; survival analysis.

Figure 1

Kaplan–Meier curves of survival free of cancer in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). Left panel: females; right panel: males. Skin cancer was not included.

Figure 2

Kaplan–Meier curves of survival free of cardiovascular disease (CVD) in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). CVD definition included myocardial infarction, angina pectoris, congestive heart failure, atrial fibrillation, and/or valvular heart disease. Left panel: females; right panel: males.

Figure 3

Kaplan–Meier curves of survival free of severe dementia in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). Left panel: females; right panel: males.

Figure 4

Kaplan–Meier curves of survival free of diabetes in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). Left panel: females; right panel: males.

Figure 5

Kaplan–Meier curves of survival free of hypertension in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). Left panel: females; Right panel: males.

Figure 6

Kaplan–Meier curves of survival free of osteoporosis in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). Osteoporosis age of onset was based on the earliest diagnosis or reported hip, wrist, and/or vertebral fracture at age 50 and older. Left panel: females; right panel: males.

Figure 7

Kaplan–Meier curves of survival free of stroke in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). Left panel: females; right panel: males.

Figure 8

Kaplan–Meier curves of survival free of morbidity in NECS controls (NECS.C, black line), LLFS controls (LLFS.C, green line), LLFS probands and siblings (LLFS.P, blue line), and NECS centenarians (NECS.P, red line). Morbidity was defined as one or more of the following: cancer, COPD, CVD, dementia, diabetes, or stroke. Left panel: females; right panel: males.

Figure 9

Estimates and 95% credible intervals of the age at which p% of subjects in the various groups had onset of disease. The inset describes the groups’ labels. Rationale for the choice of percentages p is in methods.