Genetics of aging and longevity

Abstract

⎯Lifespan is a complex quantitative trait, which makes a significant contribution to Darwinian fit-ness. The understanding of the genetic structure of longevity is a fundamental problem of the evolution of ontogeny, evolutionary genetics, and molecular gerontology. Under optimal conditions, lifespan is deter-mined by the aging rate. Aging is made up of interrelated processes that occur at the organismal, tissue, cel-lular, molecular, and genetic levels. The disturbances touch homeostasis maintenance, metabolic reactions, and transduction of intra and intercellular signals. Its other consequences are the accumulation of senescent cells, damaged organelles, and macromolecules; epigenetic changes; and genetic instability. This review sum-marizes the current knowledge of the major genetic determinants of longevity and aging. It considers genes and signaling pathways that regulate stress response, metabolism, the growth of cells and the body, preserva-tion of genome and proteome integrity, qualitative and quantitative mitochondrion composition, inflamma-tory response, apoptosis, selection of viable cells, and circadian rhythms. The redistribution of energy resources from one pathway to another can induce or inhibit the " longevity program, " improving stress resis-tance and slowing down senescence. Approaches to slowing aging and achieving healthy longevity are out-lined based on the analysis of the geroprotective potential of the regulation of the examined genes. These trends include heterochromatin recovery; retrotransposition suppression; aneuploidy elimination; resto-ration of lysosome acidity; telomere extension; suppression of chronic inflammation; elimination of protein crosslinks; elimination of senescent cells; recovery of NAD + levels; inhibition of mTOR, S6K, TGFβ, and AT1; and controlled activation of the longevity program genes FOXO, AMPK, PGC1α, and NRF2.