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The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations

Nature Aging volume 3, pages 766–775 (2023)Cite this article

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Abstract

With recent rapid progress in research on aging, there is increasing evidence that many features commonly considered to be mechanisms or drivers of aging in fact represent adaptations. Here, we examine several such features, including cellular senescence, epigenetic aging and stem cell alterations. We draw a distinction between the causes and consequences of aging and define short-term consequences as ‘responses’ and long-term ones as ‘adaptations’. We also discuss ‘damaging adaptations’, which despite having beneficial effects in the short term, lead to exacerbation of the initial insult and acceleration of aging. Features commonly recognized as ‘basic mechanisms of the aging process’ are critically examined for the possibility of their adaptation-driven emergence from processes such as cell competition and the wound-like features of the aging body. Finally, we speculate on the meaning of these interactions for the aging process and their relevance for the development of antiaging interventions.

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Fig. 1: Relationships between the causes and consequences of the aging process.
Fig. 2: Cellular senescence as an adaptation to damage in tissues.
Fig. 3: Age-related changes in DNA methylation are associated with diverse processes.
Fig. 4: Age-associated alterations of stem cells are driven to a large extent by adaptations to a degrading niche.

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Acknowledgements

We thank H. Salmonowicz who developed the original illustrations for this manuscript and N. Ring for proofreading the manuscript. The Research Group Senescence and Healing of Wounds is a collaboration between the Ludwig Boltzmann Gesellschaft and the Austrian Workers’ Compensation Board, with support from the Austrian Nationalstiftung. V.N.G. is supported by National Institute on Aging grants, the James Fickel and Michael Antonov Foundations, and the Impetus grant program. M.O. is supported by Der Wissenschaftsfonds grant nos. P35382 and P36483 and a Federation of European Biochemical Societies Excellence Award.

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Authors and Affiliations

  1. Ludwig Boltzmann Research Group Senescence and Healing of Wounds, Vienna, Austria

    Mikolaj Ogrodnik

  2. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Workers’ Compensation Board Research Center, Vienna, Austria

    Mikolaj Ogrodnik

  3. Austrian Cluster for Tissue Regeneration, Vienna, Austria

    Mikolaj Ogrodnik

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

    Vadim N. Gladyshev

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M.O. wrote the first draft. M.O. and V.N.G. extended, revised and finalized the manuscript.

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Ogrodnik, M., Gladyshev, V.N. The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations. Nat Aging 3, 766–775 (2023). https://doi.org/10.1038/s43587-023-00447-5

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