Abstract
Adipose tissue, a pivotal player in whole-body energy homeostasis and insulin sensitivity, undergoes considerable remodelling throughout the ageing process, a facet that has garnered little attention until the past decade. This Review comprehensively summarizes the dynamic metabolic, cellular and functional changes that occur in white and thermogenic adipose tissue during distinct ageing stages, across different adipose tissue depots. We emphasize the influence of ageing on different cell types within adipose tissue, including adipocytes, adipocyte progenitors, immune cells and senescent cells, and their collective effect on adipose tissue function and systemic metabolism. We also decipher the correlation between adipose tissue ageing and prevalent age-related conditions such as metabolic dysfunction-associated fatty liver disease and cardiovascular diseases. Finally, the Review delves into the potential of current anti-ageing interventions to beneficially affect adipose tissue, encompassing caloric restriction, metformin, glucagon-like peptide 1 receptor agonists and senolytics. The discussion extends to the exploration of whether targeting adipose tissue through such interventions could emerge as a prominent therapeutic strategy for mitigating age-related diseases and enhancing the healthspan and lifespan of the ageing population.
Key points
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Adipose tissue is among the first organs to undergo changes in metabolic responses and endocrine function during early ageing, considerably affecting other metabolically active organs and contributing to systemic ageing and declining metabolic health.
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White adipose tissue ages differently across anatomical depots and these alterations do not follow a linear trajectory with advancing age.
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Robust adipogenesis is triggered during the early stages of ageing, particularly in the visceral adipose tissue of male individuals. Age-specific remodelling of adipose progenitor cells unlocks their adipogenic potential.
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Therapeutic strategies that enhance white adipose tissue function, without necessarily reducing its mass, have shown promising effects in improving metabolic health in older individuals.
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Reduced thermogenic activity in brown and beige adipocytes contributes to age-related cold sensitivity, diminishing the ability of older individuals to maintain core body temperature in colder environments.
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Acknowledgements
The authors are grateful to P. Scherer (University of Texas Southwestern Medical Center), T. McLaughlin (Stanford) and Z. Zhang (Wuhan University) for their insightful suggestions and comments. Q.A.W. is supported by National Institutes of Health grants R56AG063854, R01AG063854, R01HD096152, R01DK128907, California Institute for Regenerative Medicine grant DISC0-15689 and the American Diabetes Association Junior Faculty Development Award 1-19-JDF-023.
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Wang, G., Song, A. & Wang, Q.A. Adipose tissue ageing: implications for metabolic health and lifespan. Nat Rev Endocrinol 21, 623–637 (2025). https://doi.org/10.1038/s41574-025-01142-8
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DOI: https://doi.org/10.1038/s41574-025-01142-8
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