Kim Sangkyu, Welsh David A, Cherry Katie E, Myers Leann, Jazwinski S Michal
Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Ave., SL-12, New Orleans, LA, 70112, USA,
Age (Dordr). 2013 Oct;35(5):1975-82. doi: 10.1007/s11357-012-9472-0. Epub 2012 Sep 18.
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.
老年评估中纳入的各种措施已被纳入衰弱指数（FI），该指数已被用作生存/死亡率和长寿的指标。我们的目标是了解健康衰老的遗传基础，以加强其证据基础和实用性。我们构建了一个FI作为健康衰老的定量指标，并研究了其特征和遗传分析潜力。从两项独立研究中选取了两组。一组（长寿父母后代的OLLP）由无亲属关系的参与者组成，其中至少有一位父母年龄在90岁或以上，另一组无亲属关系的参与者（短寿父母后代的OSLP），其父母均在76岁之前去世。根据34个常见健康变量计算FI34得分，并在两组之间进行比较。FI34与死亡率的相关性比实际年龄更好（即相关性更强）。OSLP的FI34平均值得比OLLP高31%（P = 0.0034）。FI34呈指数增长，在OLLP中每年以2.0%的速度加速增长（P = 0.024），在OSLP中为2.7%（P << 0.0001），因此后一组的累积增长大63%（P = 0.0002）。结果表明，两组在生命过程中健康缺陷的累积情况不同，这可能是由于与父母长寿相关的遗传因素。与此一致的是，同胞对的FI34得分显著相关，FI34的遗传度估计为0.39。最后，层次聚类表明OLLP和OSLP在衰老模式上存在差异。FI34的变异部分归因于遗传变异；因此，FI34可以作为一个适合健康衰老遗传分析的表型指标。
