Genetic Determinants of Human Life‐Span

Abstract

The contribution of genetic factors to human life‐span and longevity is recognised although the mediators and their molecular mechanisms are currently far from completely understood. However, significant advances have been recently made to unveil the genes and pathways involved in life trajectory determination in humans as well as in model organisms. In humans, more than 100 longevity candidate genes have been presented; however, with the exception of a few loci, the results tend to suffer from a lack of replication. Nevertheless, genetics appears to have moderate control over human life‐span and the impact is known to increase towards the old ages. Currently, the pathways with the most potential for harbouring longevity genes include the insulin/insulin‐like growth factor (IGF) signalling (IIS) and lipid metabolism. It remains to be seen whether future studies can pinpoint additional pathways and elucidate the remaining unexplained genetic variation in human life‐span. Key Concepts: Human life‐span is an extremely complex entity with genetic, environmental and stochastic factors modulating the longevity phenotype. The majority of the proposed longevity gene candidates appear to be population‐ and/or sex‐specific. Consistent association with human life‐span or longevity has thus far been observed for only the APOE , FOXO3 and ATK1 loci.