Species Somatic Mutation and Lifespan Correlation

Journal Club June 2022


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The Journal Club returns on June 28th at 12:00 Eastern Standard time with your host Dr. Oliver Medvedik. This month we are taking a look at a recent paper that explores species somatic mutation and lifespan correlation published in the journal Nature.


The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans [1-7]. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans [8], although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined-including variation of around 30-fold in lifespan and around 40,000-fold in body mass-the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.

Cagan, A., Baez-Ortega, A., Brzozowska, N., Abascal, F., Coorens, T., Sanders, M. A., Lawson, A., Harvey, L., Bhosle, S., Jones, D., Alcantara, R. E., Butler, T. M., Hooks, Y., Roberts, K., Anderson, E., Lunn, S., Flach, E., Spiro, S., Januszczak, I., Wrigglesworth, E., … Martincorena, I. (2022). Somatic mutation rates scale with lifespan across mammals. Nature, 604(7906), 517–524. https://doi.org/10.1038/s41586-022-04618-z
CategoryJournal Club, News
About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.