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Genetic mechanisms of aging

Czech version

Authors: Lukáš Sourada;  Petr Kuglík
Authors‘ workplace: Ústav experimentální biologie PřF MU, Brno
Published in: Čas. Lék. čes. 2020; 159: 81-87
Category: Review Article

Overview

Aging is an extremely complex phenomenon that has many manifestations at the molecular, cellular, and whole-body levels, and in some form involves virtually all living beings. It is a process characterized by a general progressive deterioration of the physiological functions of the organism leading to increased susceptibility to diseases. This article summarizes the basic features and molecular hallmarks of aging and describes some of the genetic mechanisms of this phenomenon. It deals with the particular genes and molecular pathways involved in the regulation of aging as well as promising possibilities of interventions affecting this process.

Keywords:

Genetics – aging – longevity genes – sirtuins – Telomeres

Sources
  1. Weismann A. Über die Dauer des Lebens: ein Vortrag. G. Fischer, Jena, 1882.
  2. Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet 2018; 19: 371–384.
  3. Jones OR, Scheuerlein A, Salguero-Gómez R et al. Diversity of ageing across the tree of life. Nature 2014; 505: 169–173.
  4. Sweeney BW, Vannote RL. Population synchrony in mayflies: a predator satiation hypothesis. Evolution 1982; 36: 810–821.
  5. Cohen AA. Aging across the tree of life: The importance of a comparative perspective for the use of animal models in aging. BBA-Mol. Basis Dis 2018; 1864: 2680–2689.
  6. Dong X, Milholland B, Vijg J. Evidence for a limit to human lifespan. Nature 2016; 538: 257–259.
  7. Kenyon C. The genetics of ageing. Nature 2010; 464: 504–512.
  8. Robine JM, Allard M. The oldest human. Science 1998; 279: 1834–1835.
  9. López-Otín C, Blasco MA, Partridge L et al. The hallmarks of aging. Cell 2013; 153: 1194–1217.
  10. Strehler BL. Aging research: current and future. J Invest Dermatol 1979; 73(1): 2–7.
  11. Lenart P, Bienertová-Vašků J. Keeping up with the Red Queen: the pace of aging as an adaptation. Biogerontology 2017; 18: 693–709.
  12. Gorbunova V, Bozzella M, Seluanov A. Rodents for comparative aging studies: from mice to beavers. Age 2008; 30: 111–119.
  13. Sebastiani P, Gurinovich A, Bae H et al. Four genome-wide association studies identify new extreme longevity variants. J Gerontol A Biol Sci Med Sci 2017;72: 1453–1464.
  14. Perls TT, Wilmoth J, Levenson R et al. Life-long sustained mortality advantage of siblings of centenarians. Proc Natl Acad Sci U S A 2002; 99(12): 8442–8447.
  15. Kaplanis J, Gordon A, Shor T et al. Quantitative analysis of population-scale family trees with millions of relatives. Science 2018; 360: 171–175.
  16. Rajpathak SN, Liu Y, Ben-David O et al. Lifestyle factors of people with exceptional longevity. J Am Geriatr Soc 2011; 59: 1509–1512.
  17. Dato S, Rose G, Crocco P et al. The genetics of human longevity: an intricacy of genes, environment, culture and microbiome. Mech Ageing Dev 2017; 165: 147–155.
  18. Klass MR. A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev 1983, 22: 279–286.
  19. Murakami S, Johnson TE. A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 1996; 143: 1207–1218.
  20. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 1999; 13: 2570–2580.
  21. Morris BJ. Seven sirtuins for seven deadly diseases of aging. Free Radical Bio Med 2013; 56: 133–171.
  22. Fontana L, Partridge L, Longo VD. Extending healthy life span: from yeast to humans. Science 2010; 328: 321–326.
  23. Willcox B. J, Tranah G. J, Chen R et al. The FoxO3 gene and cause-specific mortality. Aging Cell 2016; 15: 617–624.
  24. Harrison DE, Strong R, Sharp ZD et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009; 460: 392–395.
  25. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012; 149: 274–293.
  26. Soerensen M, Dato S, Tan Q et al. Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL-6 with human longevity. Age 2013; 35: 487–500.
  27. Mahley RW. Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. J Mol Med 2016; 94: 739–746.
  28. Bojesen SE, Nordestgaard BG. The common germline Arg72Pro polymorphism of p53 and increased longevity in humans. Cell Cycle 2008; 7: 158–163.
  29. Debrabant B, Soerensen M, Flachsbart F et al. Human longevity and variation in DNA damage response and repair: study of the contribution of sub-processes using competitive gene-set analysis. Eur J Hum Genet 2014; 22: 1131–1136.
  30. Rode L, Nordestgaard BG, Bojesen SE. Peripheral blood leukocyte telomere length and mortality among 64 637 individuals from the general population. J Natl Cancer Inst 2015; 107: djv074.
  31. Morris BJ, Willcox BJ, Donlon TA. Genetic and epigenetic regulation of human aging and longevity. BBA-Mol Basis Dis 2019; 1865: 1718–1744.
  32. Cabreiro F, Au C, Leung KY et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 2013; 153: 228–239.
  33. Berman AY, Motechin RA, Wiesenfeld MY et al. The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol 2017; 1: 35.
  34. Kirkland JL, Tchkonia T, Zhu Y et al. The clinical potential of senolytic drugs. J Am Geriatr Soc 2017; 65: 2297–2301.
  35. Katsimpardi L, Litterman N. K, Schein PA et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 2014; 344: 630–634.
  36. Cohen HY, Miller Ch, Bitterman KJ et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 2004; 305: 390–392.
  37. Daniel M, Tollefsbol TO. Epigenetic linkage of aging, cancer and nutrition. J Exp Biol 2015; 218: 59–70.
  38. Rothwell PM, Fowkes FGR, Belch JFF et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377: 31–41.
  39. Moore SC, Patel AV, Matthews ChE et al. Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis. PLoS Med 2012; 9: e1001335.
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