Abstract
The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile genetic elements that can move from one genomic location to another; in this process, they amplify and increase their presence in genomes, sometimes to very high copy numbers. In this Review we discuss new evidence and ideas that the activity of retrotransposons, a major subgroup of transposons overall, influences and even promotes the process of ageing and age-related diseases in complex metazoan organisms, including humans. Retrotransposons have been coevolving with their host genomes since the dawn of life. This relationship has been largely competitive, and transposons have earned epithets such as ‘junk DNA’ and ‘molecular parasites’. Much of our knowledge of the evolution of retrotransposons reflects their activity in the germline and is evident from genome sequence data. Recent research has provided a wealth of information on the activity of retrotransposons in somatic tissues during an individual lifespan, the molecular mechanisms that underlie this activity, and the manner in which these processes intersect with our own physiology, health and well-being.
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Acknowledgements
The following funding sources are acknowledged: V.G. and A.S., NIH R37 AG046320, R01 AG027237, P01 AG047200 and P01 AG051449; P.M. and J.D.B., NIH P01 AG051449 and R21 CA235521; F.H.G., NIH R01 AG056306, R01 AG057706, the American Heart Association, Paul G. Allen Frontiers Group Grant no. 19PABHI34610000, the Grace Foundation, the JPB Foundation and A. C. Merle-Smith; J.A.K., NIH P20 GM119943 and P01 AG051449; J.R.T., NIH K99 AG057812; S.L.H., NIH R01 AG024353, P01 AG051449 and R01 AG067306; and J.M.S., NIH R01 AG016694 and P01 AG051449.
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J.M.S. conceived the review. J.M.S., V.G., A.S., P.M., W.M., D.F., J.D.B., S.B.L., F.H.G., J.A.K., A.P.P., T.A.W., J.R.T. and S.L.H. collectively wrote and edited the manuscript.
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V.G. and A.S. are cofounders of Persimmon Bio; V.G. is a member of the scientific advisory board (SAB) of DoNotAge, Centaura and Elysium; J.D.B. is a founder of Neochromosome, founder and director of CDI Labs, and founder and SAB member of ReOpen Diagnostics, and is also an SAB member of Sangamo, Modern Meadow, Sample6 and the Wyss Institute; F.H.G. is an SAB member of Transposon Therapeutics; and J.M.S. is a cofounder and SAB chair of Transposon Therapeutics and consults for Atropos Therapeutics, Gilead Sciences and Oncolinea.
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Peer review information Nature thanks Peter Adams, Jan Vijg and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Gorbunova, V., Seluanov, A., Mita, P. et al. The role of retrotransposable elements in ageing and age-associated diseases. Nature 596, 43–53 (2021). https://doi.org/10.1038/s41586-021-03542-y
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DOI: https://doi.org/10.1038/s41586-021-03542-y
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