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Translational regulation in stress biology

Nature Cell Biology (2025)Cite this article

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Abstract

Organisms must constantly respond to stress to maintain homeostasis, and the successful implementation of cellular stress responses is directly linked to lifespan regulation. In this Review we examine how three age-associated stressors—loss of proteostasis, oxidative damage and dysregulated nutrient sensing—alter protein synthesis. We describe how these stressors inflict cellular damage via their effects on translation and how translational changes can serve as both sensors and responses to the stressor. Finally, we compare stress-induced translational programmes to protein synthesis alterations that occur with age and discuss whether these changes are adaptive or deleterious to longevity and healthy ageing.

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Fig. 1: Translational response to proteotoxic stress.
Fig. 2: Translational response to oxidative stress.
Fig. 3: Translational regulation of autophagy.
Fig. 4: Stress responsiveness in ageing.

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Acknowledgements

We thank all members of the Dillin laboratory for their constructive discussion. Figures were created in BioRender. A.D. is supported by the Howard Hughes Medical Institute and N.R.G. is a Howard Hughes Medical Institute Fellow of the Jane Coffin Childs Memorial Fund.

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  1. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA

    Naomi R. Genuth & Andrew Dillin

  2. Howard Hughes Medical Institute, University of California, Berkeley, CA, USA

    Naomi R. Genuth & Andrew Dillin

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  1. Naomi R. Genuth
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  2. Andrew Dillin
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N.R.G. prepared the manuscript and figures with guidance from A.D. All authors reviewed and edited the manuscript.

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Genuth, N.R., Dillin, A. Translational regulation in stress biology. Nat Cell Biol (2025). https://doi.org/10.1038/s41556-025-01765-z

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