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The case for space as a model of accelerated aging

Nature Aging (2026)Cite this article

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Abstract

Aging is a complex biological and societal challenge, where modest advances can yield substantial clinical and economic benefits. While model organisms have uncovered key mechanisms of aging, their physiological relevance to humans remains limited. Astronauts offer a uniquely informative human model: despite being healthy and highly selected, they exhibit many hallmarks of aging and experience comparable declines in cardiovascular, musculoskeletal, cognitive and immune function—often on accelerated timelines. These changes are largely driven by four core exposures of the space environment: microgravity, circadian disruption, ionizing radiation and social isolation. Here, by tracing how environmental factors affect biological processes such as mitochondrial dysfunction, altered cytoskeletal dynamics, chronic inflammation and other canonical hallmarks of aging, we position spaceflight as a powerful model for human aging—one that unites environmental stress biology, multi-omic systems approaches and clinical research to advance both astronaut health and the healthspan of aging populations on Earth.

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Fig. 1: Shared environmental stressors linking the spaceflight and terrestrial exposomes to aging pathways and disease.
Fig. 2: Hallmarks of aging in spaceflight.
Fig. 3: An incremental model of morbidity within normal and astronaut populations.
Fig. 4: Proposed mechanisms behind cardiovascular decline in aging and spaceflight.
Fig. 5: Unloading drives bone density loss, a conserved mechanism of osteoporosis in astronauts and older adults.
Fig. 6: Proposed mechanisms of neurocognitive decline in spaceflight and aging.
Fig. 7: Proposed mechanisms of immune dysfunction in spaceflight and aging.

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Acknowledgements

We thank J. Baechle for discussions related to this manuscript. This work was supported in part through funds derived from the Buck Institute for Research on Aging (to D.A.W. and D.F.), the Buck Bioinformatics Core (to D.F.), the Natural Sciences and Engineering Research Council of Canada (NSERC, grant RGPIN-2024-05532, to D.A.W.) and the Huiying Memorial Foundation (to D.A.W.).

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Authors and Affiliations

  1. Buck Institute for Research on Aging, Novato, CA, USA

    Max Manwaring-Mueller, Huixun Du, Taylor R. Valentino, Matias Fuentealba, Alexander Chebykin, Fei Wu, David Furman & Daniel A. Winer

  2. Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA

    Huixun Du & Daniel A. Winer

  3. Buck AI Platform, Buck Institute for Research on Aging, Novato, CA, USA

    Matias Fuentealba & David Furman

  4. Dominican University of California, San Rafael, CA, USA

    Alexander Chebykin & Daniel A. Winer

  5. Stanford 1,000 Immunomes Project, Stanford School of Medicine, Stanford University, Stanford, CA, USA

    David Furman

  6. Instituto de Investigaciones en Medicina Traslacional (IIMT), Universidad Austral, CONICET, Pilar, Argentina

    David Furman

  7. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Daniel A. Winer

  8. Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, Ontario, Canada

    Daniel A. Winer

  9. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    Daniel A. Winer

Authors
  1. Max Manwaring-Mueller
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  2. Huixun Du
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  3. Taylor R. Valentino
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  4. Matias Fuentealba
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  5. Alexander Chebykin
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  6. Fei Wu
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  7. David Furman
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  8. Daniel A. Winer
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Contributions

All authors contributed to the design and writing of the manuscript and the generation of the figures.

Corresponding authors

Correspondence to David Furman or Daniel A. Winer.

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Competing interests

D.F. and D.A.W. are cofounders of Cosmica Biosciences, a company that studies altered biological aging in spaceflight exposures. F.W. is a stakeholder in Cosmica Biosciences. The remaining authors declare no competing interests.

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Nature Aging thanks Jeremy Teo, who co-reviewed with Mei ElGindi; Charles Wang, who co-reviewed with Zhong Chen; and Evandro Fei Fang for their contribution to the peer review of this work.

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Manwaring-Mueller, M., Du, H., Valentino, T.R. et al. The case for space as a model of accelerated aging. Nat Aging (2026). https://doi.org/10.1038/s43587-026-01105-2

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