Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Reverting to old theories of ageing with new evidence for the role of somatic mutations

Nature Reviews Genetics (2022)Cite this article

Subjects

With age, somatic mutations accumulate in the genome of healthy individuals, but the functional outcome of this increased mutational load has been unclear. Recent sequencing data support a functional role for somatic mutations in ageing and age-associated diseases.

More than 60 years ago, Szilard postulated that ageing could result from the accumulation of somatic mutations1. This hypothesis is supported by premature ageing syndromes being predominantly caused by disruption of genes involved in DNA maintenance and repair. Somatic mutations undoubtedly accumulate in the genome of healthy individuals as they age and are recognized as a crucial trigger for the expansion of malignant and non-malignant clones. However, whether an increased mutational load causally contributes to the progressive loss of function observed in aged tissues is still a matter of debate.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Szilard, L. Proc. Natl. Acad. Sci. USA 45, 30–45 10 (1959).

  2. Sun, S., Wang, Y., Maslov, A. Y., Dong, X. & Vijg, J. Nucleic Acids Res. 50, D1100–D1108 (2021).

  3. Franco, I., Revechon, G. & Eriksson, M. Aging Cell https://doi.org/10.1111/acel.13613 (2022).

  4. Cagan, A. et al. Nature 604, 517–524 (2022).

  5. Schumacher, B., Pothof, J., Vijg, J. & Hoeijmakers, J. H. J. Nature 592, 695–703 (2021).

  6. Zhang, L. et al. Sci. Adv. 7, eabj3284 (2021).

  7. Thompson, D. J. et al. Nature 575, 652–657 (2019).

  8. Miller, M. B. et al. Nature 604, 714–722 (2022).

  9. Abascal, F. et al. Nature 593, 405–410 (2021).

  10. Franco, I. et al. Genome Biol. 20, 285 (2019).

Download references

Acknowledgements

We thank R. Sitia and A. Boletta for discussions. I.F. is supported by Marie Sklodowska-Curie individual fellowship 896832-SoMuKT.

Author information

Authors and Affiliations

  1. Cystic Kidney Disorders Unit, Division of Genetics and Cell Biology, IRCCS Ospedale San Raffaele, Milan, Italy

    Irene Franco

  2. Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden

    Maria Eriksson

Authors
  1. Irene Franco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Eriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Irene Franco or Maria Eriksson.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Franco, I., Eriksson, M. Reverting to old theories of ageing with new evidence for the role of somatic mutations. Nat Rev Genet (2022). https://doi.org/10.1038/s41576-022-00513-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1038/s41576-022-00513-5

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing