Abstract
Metabolic processes shape ageing and longevity at multiple levels. Emerging evidence shows that many of these processes are orchestrated within and between cellular organelles. Organelles function not only as metabolic reactors but also as signalling hubs, and their coordination plays crucial roles in maintaining cellular homeostasis and promoting organismal fitness. Rather than acting in isolation, organelles engage in dynamic crosstalk through membrane contact sites, metabolite exchange and signalling interplay. In recent years, organelles have been increasingly recognized as critical regulators of ageing and longevity. Here we summarize age-related organellar changes, highlight organelle-mediated intra- and intercellular signalling communication in lifespan and healthspan regulation, and discuss the active roles of organelles in microbiome–host interactions and transgenerational inheritance in regulating longevity. We further outline how longevity-promoting interventions influence organelles, and provide perspectives on how future technological advances may further accelerate progress in this emerging research topic.
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We thank Howard Hughes Medical Institute for financial support.
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Conceptualization was provided by P.M., M.P. and M.C.W. The literature review was carried out by P.M., M.P. and M.C.W. Figures were generated by P.M. and M.P. The original draft was written by P.M. and M.P., and the paper was reviewed and edited by P.M., M.P. and M.C.W. Supervision was provided by M.C.W.
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Mannino, P., Park, M. & Wang, M.C. Organellar insights in ageing and longevity. Nat Cell Biol 28, 861–874 (2026). https://doi.org/10.1038/s41556-026-01927-7
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DOI: https://doi.org/10.1038/s41556-026-01927-7
