Which gene variants contribute to longevity? To find out, Zhengdong Zhang, Ph.D., and colleagues conducted the largest whole-exome sequencing study to date of centenarians. (The exome is the functional part of the genome, containing all of its exons, i.e., the portions of genes that code for proteins.) In findings reported in September in Nature Aging, the researchers found that rare gene variants in the Wnt signaling pathway (consisting of 19 genes) had a pro-longevity effect in those centenarians possessing APOE4, a well-known and common gene variant associated with risk for Alzheimer's disease, hyperlipidemia, atherosclerosis, and a shorter life span. The results suggest that the Wnt-signaling gene variants counteract the adverse health effects associated with the APOE4 gene. Drugs designed to mimic the effects of those protective Wnt signaling gene variants could may benefit people who carry the APOE4 gene variant and possibly other people as well.

Dr. Zhang is a professor of genetics at Einstein.