Encyclopedia of Gerontology and Population Aging

Living Edition
| Editors: Danan Gu, Matthew E. Dupre

Mutation Load and Aging

  • Diddahally GovindarajuEmail author
  • Hideki Innan
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-69892-2_733-1



Mutations are responsible for all inherited variation. By definition, most mutations exert deleterious (harmful) effects on viability and reproduction of an organism, also known as Darwinian fitness. Therefore, following Crow and Kimura (1963), mutation load could be defined as “the proportion by which the fitness of the average genotype in the population is reduced (due to recurrent mutations) in comparison with the best genotype (relatively free from mutations).” Mutational theory of aging deals with the influence of one or more mutations on the life span of individuals.


Inherited variation is fundamental to evolution, and mutations are the major causes of phenotypic diversity at all levels of biological hierarchy of organisms, on which selection acts. All organisms have their own species-specific life span, defined as the average life expectancy between birth and...

This is a preview of subscription content, log in to check access.


  1. Allison B (2016) Divergence of mechanistic pathways mediating aging and developmental programming of cardiovascular diseases. FASEB J 30:1968–1975CrossRefGoogle Scholar
  2. Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, Vitale L, Pelleri MC, Tassani S, Piva F, Perez-Amodio S, Strippoli P, Canaider S (2013) An estimation of the number of cells in the human body. Ann Hum Biol 40:463–471CrossRefGoogle Scholar
  3. Budovsky A, Craig T, Wang B, Tacutu R, Csordas A, Lourengo J, Fraifeld VE, de Magalhaes JP (2013) LogevityMap: a database of human genetic variants associated with longevity. Trends Genet 29:559–560CrossRefGoogle Scholar
  4. Buja A, Volfosvsky N, Krieger AM, Lord C, Lash AE, Wigler M Iossifov I (2018) Damaging de novo mutations diminish motor skills in children on the autism spectrum. Proc. Natl. Acad. Sci. USA 115:E1859–E18866CrossRefGoogle Scholar
  5. Campbell CD, Eichler EE (2013) Properties and rates of germline mutations in humans. Trends Genet 29:575–584CrossRefGoogle Scholar
  6. Charlesworth B (2012) The effects of deleterious mutations on evolution at linked sites. Genetics 190:5–22CrossRefGoogle Scholar
  7. Crow JF (2000) The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet 1:40–47CrossRefGoogle Scholar
  8. Crow JF (2012) Upsetting the dogma: germline selection in human males. PLoS Genet 8:e1002535CrossRefGoogle Scholar
  9. Crow JF, Kimura M (1963) The theory of genetic loads. In: Proceedings of the XI international congress of genetics, vol 3, pp 495–506Google Scholar
  10. Girirajan S, Campbellm CD, Eichler EE (2011) Human copy number variation and complex genetic disease. Annu Rev Genet 45:203–226CrossRefGoogle Scholar
  11. Govindaraju DR (2015) Evolutionary genetic bases of longevity and senescence. Adv Exp Med Biol 847:1–44CrossRefGoogle Scholar
  12. Haldane JBS (1935) The rate of spontaneous mutation of a human gene. J Genet 31:317–326CrossRefGoogle Scholar
  13. Haldane JBS (1941) New paths in genetics. Allen and Unwin, LondonGoogle Scholar
  14. Jamuar SS, Lam A-T, Kircher M, D’Gama AM, Wang J, Barry BJ, Zhang X, Hill RS, Partlow JN, Rozzo A, Servattalab S, Mehta BK, Topku M, Amrom D, Andermann E, Dan B, Parrini E, Guerrini R, Scheffer IE et al (2014) Somatic mutations in cerebral cortical malformations. N Engl J Med 371:733–743CrossRefGoogle Scholar
  15. Lee-Six H, Øbro NF, Shepherd MS, Grossmann S, Dawson K, Belmonte M, Osborne RJ, Huntly BJP, Martincorena I, Anderson E, O'Neill L, Stratton MR, Laurenti E, Green AR, Kent DG, Campbell PJ (2018) Population dynamics of normal human blood inferred from somatic mutations. Nature 561:473–478CrossRefGoogle Scholar
  16. Lodato MA, Rodin RE, Bohrson CL, Coulter ME, Barton AR, Kwon M, Sherman MA, Vitzthum CM, Luquette LJ, Yandava CN, Yang P, Chittenden TW, Hatem NE, Ryu SC, Woodworth MB, Park PJ, Walsh CA (2018) Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 359(6375):555–559CrossRefGoogle Scholar
  17. Lynch M, Bürger R, Butcher D, Gabriel W (1993) The mutational meltdown in asexual populations. J Hered 84:339–344CrossRefGoogle Scholar
  18. Lynch M (2010) Rate, molecular spectrum and consequence of human mutation. Proc. Natl. Acad. Sci USA 107:961–968CrossRefGoogle Scholar
  19. Medawar PB (1952) An unsolved problem of biology. H. K. Lewis, LondonGoogle Scholar
  20. Morelli KH, Seburn KL, Schroeder DG, Spaulding EL, Dionne LA, Cox GA, Burgess RW (2017) Severity of demyelinating and axonal neuropathy mouse models is modified by genes affecting structure and function of peripheral nodes. Cell Rep 18:3178–3191CrossRefGoogle Scholar
  21. Morton NE, Crow JF, Muller HJ (1956) An estimate of the mutational damage in man from data on consanguineous marriages. Proc Natl Acad Sci USA 42:855–863CrossRefGoogle Scholar
  22. Muller HJ (1950) Our load of mutations. Am J Hum Genet 2:111–176Google Scholar
  23. Muñoz-Espín D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15:482–496CrossRefGoogle Scholar
  24. Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246:96–98CrossRefGoogle Scholar
  25. Ori A, Toyama BH, Harris MS, Bock T, Iskar M, Bork P, Ingolia N, Hetzer M, Beck M (2015) Integrated Transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats. Cell Syst 1:224–237CrossRefGoogle Scholar
  26. Poduri A, Evrony GD, Cai X, Walsh CA (2013) Somatic mutation, genomic variation, and neurological disease. Science 341:1237758CrossRefGoogle Scholar
  27. Scherer SW, Lee C, Birney E, Altshuler DM, Eichler EE, Carter NP, Hurles ME, Feuk L (2007) Challenges and standards in integrating surveys of structural variation. Nat Genet 39:S7–15CrossRefGoogle Scholar
  28. Simmons MJ, Crow JF (1977) Mutations affecting fitness in Drosophila populations. Annu Rev Genet 11:49–78CrossRefGoogle Scholar
  29. Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci USA 45(1):30–45CrossRefGoogle Scholar
  30. Toriello HV, Meck JM (2008) Statement on guidance for genetic counseling in advanced paternal age. Genet Med 10:457–460CrossRefGoogle Scholar
  31. Vassilieva LL, Hook AM, Lynch M (2000) The fitness effects of spontaneous mutations in Caenorhabditis Elegans. Evolution 54:1234–1246CrossRefGoogle Scholar
  32. Veltman JA, Brunner HG (2012) De novo mutations in human genetic disease. Nat Rev Genet 13:565–575CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.The Institute for Aging ResearchAlbert Einstein College of MedicineBronxUSA
  2. 2.Museum of Comparative ZoologyHarvard UniversityCambridgeUSA
  3. 3.Graduate University for Advanced StudiesHayamaJapan

Section editors and affiliations

  • Diddahally R. Govindaraju
    • 1
    • 2
  1. 1.Museum of Comparative ZoologyHarvard UniversityCambridgeUSA
  2. 2.The Institute for Aging Research, The Glenn Center for the Biology of Human AgingAlbert Einstein College of MedicineBronxUSA