Cellular metabolism and environmental interactions generate molecular damage affecting all levels of biological organization. Accumulation of this damage over time is thought to have a central role in the aging process. Insufficient attention has been paid to the role of molecular damage in aging-related phenotypes, particularly in humans, in part because of the difficulty in measuring its various forms. Recently, omics approaches have been developed that begin to address this challenge, because they can assess a sizable proportion of age-related damage at the level of small molecules, proteins, RNA, DNA, organelles and cells. This Review describes the concept of molecular damage in aging and discusses its diverse aspects from theoretical models to experimental approaches. Measurement of multiple types of damage enables studies of the role of damage in aging and lays a foundation for testing interventions that reduce the burden of molecular damage, thereby targeting aging.
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The review is based in part on a workshop, Biological Damage and Human Aging held in December 2019, sponsored by the Longevity Consortium with support from the National Institute of Aging. This work was supported by the National Institutes of Health (NIH) AG021332 (S.K.), NSF MCB-1714569, Life Extension Foundation and the Elizabeth and Thomas Plott Chair in Gerontology (S.G.C.), NIH AG064223, AG067782, AG065403 and AG047200 (V.N.G.), NIH HL121023 and AG032498 (G.T.) and NIA U19AG023122 (the Longevity Consortium).
The authors declare no competing interests.
Peer review information Nature Aging thanks the anonymous reviewers for their contribution to the peer review of this work.
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Gladyshev, V.N., Kritchevsky, S.B., Clarke, S.G. et al. Molecular damage in aging. Nat Aging 1, 1096–1106 (2021). https://doi.org/10.1038/s43587-021-00150-3
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