Understanding the role of host metabolites in the induction of immunesenescence: future strategies for keeping the ageing population healthy

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Abstract

Advancing age is accompanied by significant remodelling of the immune system, termed immune senescence, and increased systemic inflammation, termed inflammageing, both of which contribute towards an increased risk of developing chronic diseases in old age. Age-associated alterations in metabolic homeostasis have been linked with changes in a range of physiological functions, but their effects on immune senescence remains poorly understood. In this article, we review the recent literature to formulate hypotheses as to how an age-associated dysfunctional metabolism, driven by an accumulation of key host metabolites (saturated fatty acids, cholesterol, ceramides and lactate) and loss of other metabolites (glutamine, tryptophan and short-chain fatty acids), might play a role in driving immune senescence and inflammageing, ultimately leading to diseases of old age. We also highlight the potential use of metabolic immunotherapeutic strategies targeting these processes in counteracting immune senescence and restoring immune homeostasis in older adults.

Original languageEnglish
Pages (from-to)1808-1824
Number of pages17
JournalBritish Journal of Pharmacology
Volume179
Issue number9
Early online date26 Aug 2021
DOIs
Publication statusPublished - May 2022

Bibliographical note

Funding Information:
J.C. is supported by a scholarship from the MRC‐Versus Arthritis Centre for Musculoskeletal Ageing Research; J.M.L.'s work is supported by the NIHR Birmingham Biomedical Research Centre; C.M.'s work is supported by the Medical Research Council Grant MR/T016736/1; N.A.D.'s work is supported by the Academy of Medical Sciences. The views expressed here are those of the authors and not necessarily those of the Department for Health and Social Care.

Publisher Copyright:
© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Keywords

  • immunesenescence
  • inflammaging
  • lactate
  • saturated fatty acids
  • short chain fatty acids

ASJC Scopus subject areas

  • Pharmacology

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