Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 8/6/2015
Publication Date: 11/5/2016
Citation: Lai, C., Ma, Y., Parnell, L.D. 2016. Genetics and gene-environment interactions on longevity and lifespan. In: Qi, L., Editor. Gene-Environment Interactions and Human Diseases. Hauppauge, NY: Nova Science Publishers, Inc. p. 245-264.
Technical Abstract: Longevity is a complex trait and highly associated with healthspan – lifespan without major diseases. In human populations there is a large amount of variation in longevity, which can be attributed to genetics, environment, and interactions between them. The genetic contribution to longevity is about 25%. Candidate gene approaches and genome-wide association studies (GWAS) have identified many putative genetic factors that may have a role in lifespan. However, only two variants in the APOE and FOXO3 genes have shown consistent association with longevity in several studies. Many known genetic variants interact with environmental factors, particularly with diet and lifestyle, influencing risk of age-related diseases, such cardiovascular diseases (CVD), type 2 diabetes, and cancer. Little is known, however, about genotype by environment (GxE) interactions on longevity directly. A paradox has arisen with a few studies showing that long-lived individuals carry similar numbers of risk alleles as the individuals who have a normal lifespan. However, evidence suggests that long-lived individuals may carry protective genetic factors that delay the detrimental effects of risk alleles. Such genetic factors remain to be identified. Environmental factors can modify epigenetic changes, which in turn may affect the rate of aging and longevity. Understanding the molecular mechanisms of epigenetic changes on aging and longevity are important and remain to be illustrated.