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Genetics of aging and longevity

  • Published:
Russian Journal of Genetics: Applied Research

Abstract

Lifespan is a complex quantitative trait, which makes a significant contribution to Darwinian fitness. 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 determined by the aging rate. Aging is made up of interrelated processes that occur at the organismal, tissue, cellular, 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 summarizes 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, preservation of genome and proteome integrity, qualitative and quantitative mitochondrion composition, inflammatory 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 resistance and slowing down senescence. Approaches to slowing aging and achieving healthy longevity are outlined based on the analysis of the geroprotective potential of the regulation of the examined genes. These trends include heterochromatin recovery; retrotransposition suppression; aneuploidy elimination; restoration 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.

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Authors and Affiliations

  1. Institute of Biology Komi SC UrB, Russian Academy of Sciences, Syktyvkar, 167000, Russia

    A. A. Moskalev, E. N. Proshkina, A. A. Belyi & I. A. Solovyev

  2. Syktyvkar State University, Syktyvkar, 167001, Russia

    A. A. Moskalev, E. N. Proshkina, A. A. Belyi & I. A. Solovyev

  3. Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia

    A. A. Moskalev

  4. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117971, Russia

    A. A. Moskalev

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  1. A. A. Moskalev
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  2. E. N. Proshkina
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  3. A. A. Belyi
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Original Russian Text © A.A. Moskalev, E.N. Proshkina, A.A. Belyi, I.A. Solovyev, 2016, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2016, Vol. 20, No. 4, pp. 426–440.

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Moskalev, A.A., Proshkina, E.N., Belyi, A.A. et al. Genetics of aging and longevity. Russ J Genet Appl Res 7, 369–384 (2017). https://doi.org/10.1134/S2079059717040074

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