Skip to main content
SpringerLink
Log in

Mutation Load and Aging

  • Living reference work entry
  • First Online:
Encyclopedia of Gerontology and Population Aging

Synonyms

Aging; Genomic alterations; Heritable changes; Late onset disorders; Mendelian disorders

Definition

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.

Overview

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 via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Allison B (2016) Divergence of mechanistic pathways mediating aging and developmental programming of cardiovascular diseases. FASEB J 30:1968–1975

    Article  Google Scholar 

  • 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 40:463–471

    Article  Google Scholar 

  • 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 29:559–560

    Article  Google Scholar 

  • 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–E18866

    Article  Google Scholar 

  • Campbell CD, Eichler EE (2013) Properties and rates of germline mutations in humans. Trends Genet 29:575–584

    Article  Google Scholar 

  • Charlesworth B (2012) The effects of deleterious mutations on evolution at linked sites. Genetics 190:5–22

    Article  Google Scholar 

  • Crow JF (2000) The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet 1:40–47

    Article  Google Scholar 

  • Crow JF (2012) Upsetting the dogma: germline selection in human males. PLoS Genet 8:e1002535

    Article  Google Scholar 

  • Crow JF, Kimura M (1963) The theory of genetic loads. In: Proceedings of the XI international congress of genetics, vol 3, pp 495–506

    Google Scholar 

  • Girirajan S, Campbellm CD, Eichler EE (2011) Human copy number variation and complex genetic disease. Annu Rev Genet 45:203–226

    Article  Google Scholar 

  • Govindaraju DR (2015) Evolutionary genetic bases of longevity and senescence. Adv Exp Med Biol 847:1–44

    Article  Google Scholar 

  • Haldane JBS (1935) The rate of spontaneous mutation of a human gene. J Genet 31:317–326

    Article  Google Scholar 

  • Haldane JBS (1941) New paths in genetics. Allen and Unwin, London

    Google Scholar 

  • 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 371:733–743

    Article  Google Scholar 

  • 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 561:473–478

    Article  Google Scholar 

  • 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):555–559

    Article  Google Scholar 

  • Lynch M, Bürger R, Butcher D, Gabriel W (1993) The mutational meltdown in asexual populations. J Hered 84:339–344

    Article  Google Scholar 

  • Lynch M (2010) Rate, molecular spectrum and consequence of human mutation. Proc. Natl. Acad. Sci USA 107:961–968

    Article  Google Scholar 

  • Medawar PB (1952) An unsolved problem of biology. H. K. Lewis, London

    Google Scholar 

  • 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 18:3178–3191

    Article  Google Scholar 

  • 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 42:855–863

    Article  Google Scholar 

  • Muller HJ (1950) Our load of mutations. Am J Hum Genet 2:111–176

    Google Scholar 

  • Muñoz-Espín D, Serrano M (2014) Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 15:482–496

    Article  Google Scholar 

  • Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246:96–98

    Article  Google Scholar 

  • 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 1:224–237

    Article  Google Scholar 

  • Poduri A, Evrony GD, Cai X, Walsh CA (2013) Somatic mutation, genomic variation, and neurological disease. Science 341:1237758

    Article  Google Scholar 

  • 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:S7–15

    Article  Google Scholar 

  • Simmons MJ, Crow JF (1977) Mutations affecting fitness in Drosophila populations. Annu Rev Genet 11:49–78

    Article  Google Scholar 

  • Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci USA 45(1):30–45

    Article  Google Scholar 

  • Toriello HV, Meck JM (2008) Statement on guidance for genetic counseling in advanced paternal age. Genet Med 10:457–460

    Article  Google Scholar 

  • Vassilieva LL, Hook AM, Lynch M (2000) The fitness effects of spontaneous mutations in Caenorhabditis Elegans. Evolution 54:1234–1246

    Article  Google Scholar 

  • Veltman JA, Brunner HG (2012) De novo mutations in human genetic disease. Nat Rev Genet 13:565–575

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA

    Diddahally Govindaraju

  2. Museum of Comparative Zoology, Harvard University, Cambridge, MA, USA

    Diddahally Govindaraju

  3. Graduate University for Advanced Studies, Hayama, Kanagawa, Japan

    Hideki Innan

Authors
  1. Diddahally Govindaraju
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideki Innan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diddahally Govindaraju .

Editor information

Editors and Affiliations

  1. Population Division, UN Dept of Economic Social Affairs Population Division, New York, NY, USA

    Danan Gu

  2. Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA

    Matthew E. Dupre

Section Editor information

  1. Museum of Comparative Zoology, Harvard University, Cambridge, MA, USA

    Diddahally R. Govindaraju

  2. The Institute for Aging Research, The Glenn Center for the Biology of Human Aging, Albert Einstein College of Medicine, Bronx, NY, USA

    Diddahally R. Govindaraju

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Govindaraju, D., Innan, H. (2019). Mutation Load and Aging. In: Gu, D., Dupre, M. (eds) Encyclopedia of Gerontology and Population Aging. Springer, Cham. https://doi.org/10.1007/978-3-319-69892-2_733-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-69892-2_733-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-69892-2

  • Online ISBN: 978-3-319-69892-2

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation