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Enhancing immunity during ageing by targeting interactions within the tissue environment

Nature Reviews Drug Discovery volume 24, pages 300–315 (2025) Cite this article

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Abstract

Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as ‘inflammageing’. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this cycle, therapies are needed that target the interactions between the altered tissue environment and the immune system instead of targeting each component alone. We discuss the relative merits and drawbacks of therapies that are directed at eliminating senescent cells (senolytics) and those that inhibit inflammation (senomorphics) in the context of tissue niches. Furthermore, we discuss therapeutic strategies designed to directly boost immune cell function and improve immune surveillance in tissues.

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Fig. 1: Senescence and inflammageing in young and old skin.
The alternative text for this image may have been generated using AI.
Fig. 2: Key cellular pathways in senescence and therapeutics that target them.
The alternative text for this image may have been generated using AI.
Fig. 3: The cycle of senescence and inflammageing.
The alternative text for this image may have been generated using AI.
Fig. 4: Interventions that target tissue environments or immune cells.
The alternative text for this image may have been generated using AI.

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Acknowledgements

This work was funded by The Medical Research Council grant (MR/T030534/1), Medical Research Council Grand Challenge in Experimental Medicine grant (MICA; MR/M003833/1), the British Skin Foundation (BSF5012) and the LEO Foundation grant (LF-OC-19-000192) and the British Biotechnology and Biological Research Council grant (BB/Y003365/1) to A.N.A.

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    Olivia V. Bracken, Roel P. H. De Maeyer & Arne N. Akbar

  2. Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK

    Roel P. H. De Maeyer

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Bracken, O.V., De Maeyer, R.P.H. & Akbar, A.N. Enhancing immunity during ageing by targeting interactions within the tissue environment. Nat Rev Drug Discov 24, 300–315 (2025). https://doi.org/10.1038/s41573-024-01126-9

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