Successful aging: from phenotype to genotype.

Despite worldwide interest in the increasing human "healthspan," inadequate experimental attention has been dedicated to identifying genetic influences on successful aging beyond those that influence longevity alone. Although it is an under-studied topic, some promising leads have emerged from the existing genetic studies of successful aging. Here we describe the results of a systematic review of published family, twin, linkage, and association studies of successful aging that evaluated at least one other characteristic of healthy aging in addition to longevity. We identified 29 studies that met our criteria. Although methodological inconsistencies in sampling and phenotypes were frequent, we found evidence for a substantial genetic contribution to successful aging, including several specific genes (APOE, GSTT1, IL6, IL10, PON1, and SIRT3) that are promising candidates for future molecular genetic research. In addition to reviewing this literature, we provide recommendations for advancing our understanding of the genetic basis of successful aging.