Approximately 25–32% of the overall variation in adult lifespan is accounted for by genetic differences that become particularly important for survival after the age of 60.
Forkhead box O3 protein (FOXO3) is a transcription factor involved in the regulation of genes involved in many cellular processes, including DNA repair, tumor suppression, immune function, and resistance to oxidative stress. Some variants of FOXO3 are associated with longevity in humans.
FOXO3 is on chromosome 6.
FOXO3A encodes a key regulator of the insulin–IGF1 signaling pathway that is known to influence metabolism and lifespan.
A study of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987–13992] and 1,762 German centenarians/nonagenarians and younger controls provided evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. Replication in a French centenarian sample generated a trend that supported the previous results.
rs9400239 (C,T and T,T) has been associated with increased lifespan. The T allele is the one associated with longevity.
Centenarians represent the top percentiles of their respective birth cohort-specific age distributions and have outlived most of their peers by several decades. Only 4% of male and 5.6% of female 90-year-olds and 15–17% of 95-year-olds in Germany are likely to become 100 years themselves. Centenarians represent a highly selected phenotype. The genetic contribution to survival is strongest at very advanced ages, centenarians may be particularly enriched for beneficial variants in “longevity assurance genes”.
rs2802288 (A;G and AA), has been associated with increased lifespan. The A allele is the one associated with longevity.
rs2764264 (C;T), has been associated with increased lifespan. The C allele is the one associated with longevity, particularly among men.
rs2802292 (G;T) has been associated with increased lifespan. The G allele is the one associated with longevity.
rs1935949 (C;T) demonstrated a significant association with longevity but only among women.