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Molecular damage in aging

Nature Aging volume 1, pages 1096–1106 (2021)Cite this article

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Abstract

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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Fig. 1: Molecular damage is a central element of aging concepts.
Fig. 2: The burden of damage expands with age and affects cellular biomolecules at all levels of biological hierarchy.
Fig. 3: A prototypic example of damage in the form of amino acid residues.

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Acknowledgements

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).

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Authors and Affiliations

  1. Department of Medicine, Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Vadim N. Gladyshev & Bohan Zhang

  2. Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Stephen B. Kritchevsky

  3. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA

    Steven G. Clarke

  4. Molecular Biology Institute, University of California, Los Angeles, CA, USA

    Steven G. Clarke

  5. Department of Development and Molecular Biology, Albert Einstein College of Medicine, New York, NY, USA

    Ana Maria Cuervo

  6. Institute for Aging Studies, Albert Einstein College of Medicine, New York, NY, USA

    Ana Maria Cuervo

  7. West Coast Metabolomics Center, University of California Davis, Davis, CA, USA

    Oliver Fiehn

  8. Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK

    João Pedro de Magalhães

  9. San Francisco Coordinating Center, California Pacific Medical Center, Research Institute, San Francisco, CA, USA

    Theresa Mau, Gregory J. Tranah & Steven R. Cummings

  10. Institute for Systems Biology, Seattle, WA, USA

    Michal Maes & Robert L. Moritz

  11. Institute of the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN, USA

    Laura J. Niedernhofer

  12. De Duve Institute, Université Catholique de Louvain, Bruxelles, Belgium

    Emile Van Schaftingen

  13. Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Université Catholique de Louvain, Bruxelles, Belgium

    Emile Van Schaftingen

  14. Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia-School of Medicine, Charlottesville, VA, USA

    Kenneth Walsh & Yoshimitsu Yura

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  1. Vadim N. Gladyshev
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Contributions

V.N.G. and S.B.K. were responsible for conception and design, drafting and substantial revisions. S.G.C., B.Z. and T.M. were responsible for drafting, creation of figures and substantial revision. A.M.C., O.F., J.P.M., M.M., R.M., E.V.S., G.T., K.W. and Y.Y. were responsible for drafting and substantial revisions. L.J.N. was responsible for drafting, creation of tables and substantial revisions. S.R.C. was responsible for conception, design, oversight, drafting and substantial revisions.

Corresponding author

Correspondence to Steven R. Cummings.

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The authors declare no competing interests.

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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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