INTERACTIONS BETWEEN GENES FROM AGING-RELATED PATHWAYS: IMPACT ON HUMAN LONGEVITY

ABSTRACT: Abstract Role of genetic interactions (GxG) in human longevity remains poorly understood. We hypothesized that GxG between genes from biologically connected pathways involved in aging may impact longevity. To test this hypothesis, we selected 53 candidate genes from the aging-related pathways (IGF-1/AKT/FOXO3A, TP53/P21/P16, and mTOR/S6K mediated) that are known to jointly influence outcomes of cell responses to stress and damage, such as apoptosis, senescence, growth/proliferation, and autophagy. We evaluated the effects of interactions between SNPs in these genes on longevity in LLFS and CARe data. RESULTS: The IGF1R, PPARGC1A and BCL2 genes were consistently involved in top GxG effects (p<10-6) on survival in the oldest old (85+ and 95+). One SNP, rs2970870 in PPARGC1A gene, was broadly

SUBMITTER: Ukraintseva S 

PROVIDER: S-EPMC6845781 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature