Various measures incorporated in geriatric assessment have found their way into frailty indices (FIs), which have been used as indicators of survival/mortality and longevity. Our goal is to understand the genetic basis of healthy aging to enhance its evidence base and utility. We constructed a FI as a quantitative measure of healthy aging and examined its characteristics and potential for genetic analyses. Two groups were selected from two separate studies. One group (OLLP for offspring of long-lived parents) consisted of unrelated participants at least one of whose parents was age 90 or older, and the other group of unrelated participants (OSLP for offspring of short-lived parents), both of whose parents died before age 76. FI34 scores were computed from 34 common health variables and compared between the two groups. The FI34 was better correlated than chronological age with mortality. The mean FI34 value of the OSLP was 31 % higher than that of the OLLP (P = 0.0034). The FI34 increased exponentially, at an instantaneous rate that accelerated 2.0 % annually in the OLLP (P = 0.024) and 2.7 % in the OSLP (P < < 0.0001) consequently yielding a 63 % larger accumulation in the latter group (P = 0.0002). The results suggest that accumulation of health deficiencies over the life course is not the same in the two groups, likely due to inheritance related to parental longevity. Consistent with this, sib pairs were significantly correlated regarding FI34 scores, and heritability of the FI34 was estimated to be 0.39. Finally, hierarchical clustering suggests that the OLLP and OSLP differ in their aging patterns. Variation in the FI34 is, in part, due to genetic variation; thus, the FI34 can be a phenotypic measure suitable for genetic analyses of healthy aging.
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This study was supported by grants from the National Institute on Aging of the National Institutes of Health (K01AG027905 to SK and P01AG022064 to SMJ), by the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001–06)-02] (to SMJ), and by the Louisiana Board of Regents RC/EEP Fund through the Tulane-LSU CTRC at LSU Interim University Hospital. We thank the CTRC for nursing services, subject testing, and blood draw, and the core lab support for blood sample processing. We also thank the people of Louisiana for participation in our studies. The corresponding authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
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Kim, S., Welsh, D.A., Cherry, K.E. et al. Association of healthy aging with parental longevity. AGE 35, 1975–1982 (2013). https://doi.org/10.1007/s11357-012-9472-0