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Unlocking longevity through the comparative biology of aging

Nature Aging volume 5, pages 1686–1703 (2025)Cite this article

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Abstract

The comparative biology of aging leverages the remarkable diversity in aging rates and lifespans across species to uncover naturally evolved adaptations that promote longevity, disease resistance and injury resilience. The beauty of comparative biology is that it discovers adaptations that evolved outside of the protected laboratory environment, shaped by natural selection under real-world pressures. In this Review, we outline key approaches in comparative biology of aging studies, including the study of public mechanisms, which are shared between species, and private mechanisms, which are species-specific. Additionally, we present insights gained through high-throughput omics technologies—including genomics, transcriptomics, epigenomics, proteomics and metabolomics—and illustrate how these findings advance our understanding of how to ameliorate the hallmarks of aging, enhance cancer resistance and improve regeneration, with a focus on mammals. Finally, we offer practical guidance for designing and interpreting comparative studies aimed at understanding and translating longevity mechanisms.

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Fig. 1: Schematic explanation of the two approaches used in the comparative biology of aging.
Fig. 2: Overview of animal groups suited for studying the correlation of a trait with MLS, disease resistance or injury resilience.
Fig. 3: Selection of species with unique characteristics.
Fig. 4: Species-specific adaptations of the immune system.
Fig. 5: Animal group- or species-specific adaptations to increase genome stability.
Fig. 6: Unique mechanisms for increasing cancer resistance.

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Acknowledgements

Research in the laboratories of V.G. and A.S. is supported by grants from the US National Institute on Aging, the Impetus Grant, the Hevolution Foundation, the Michael Antonov Foundation and the Milky Way Research Foundation.

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Authors and Affiliations

  1. Department of Biology, University of Rochester, Rochester, NY, USA

    Cheyenne Rechsteiner, Francesco Morandini, Sei Joong Kim, Andrei Seluanov & Vera Gorbunova

  2. Department of Medicine, University of Rochester, Rochester, NY, USA

    Andrei Seluanov & Vera Gorbunova

Authors
  1. Cheyenne Rechsteiner
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  2. Francesco Morandini
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  3. Sei Joong Kim
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  4. Andrei Seluanov
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  5. Vera Gorbunova
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Contributions

C.R., F.M., S.J.K., A.S. and V.G. participated in the writing of this review. C.R. conceptualized and drew the original figures.

Corresponding authors

Correspondence to Andrei Seluanov or Vera Gorbunova.

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Competing interests

V.G. is a scientific advisor to DoNotAge, Matrix Bio, Genflow Biosciences, Elysium, BellSant and WndrHLTH. The other authors declare no competing interests.

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Nature Aging thanks Jean-François Lemaître, Dario Riccardo Valenzano and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Rechsteiner, C., Morandini, F., Kim, S.J. et al. Unlocking longevity through the comparative biology of aging. Nat Aging 5, 1686–1703 (2025). https://doi.org/10.1038/s43587-025-00945-8

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