The role of genetic variants in human longevity

Human longevity is a complex phenotype with a strong genetic predisposition. Increasing evidence has revealed the genetic antecedents of human longevity. This article aims to review the data of various case/control association studies that examine the difference in genetic polymorphisms between long-lived people and younger subjects across different human populations. There are more than 100 candidate genes potentially involved in human longevity; this article particularly focuses on genes of the insulin/IGF-1 pathway, FOXO3A, FOXO1A, lipoprotein metabolism (e.g., APOE and PON1), and cell-cycle regulators (e.g., TP53 and P21). Since the confirmed genetic components for human longevity are few to date, further precise assessment of the genetic contributions is required. Gaining a better understanding of the contribution of genetics to human longevity may assist in the design of improved treatment methods for age-related diseases, delay the aging process, and, ultimately, prolong the human lifespan.

Research highlights▶ Genetic polymorphisms of insulin/insulin-like growth factor-1 (IIS) signaling pathway influence human longevity. ▶ Variants of FOXO3A link to longevity across different human populations. ▶ Variants of genes involved in lipoprotein metabolism, and cell-cycle regulators contribute to human longevity.