Metabolic homeostasis of tissue macrophages across the lifespan.

Macrophages are present in almost all organs. Apart from being immune sentinels, tissue-resident macrophages (TRMs) have organ-specific functions that require a specialized cellular metabolism to maintain homeostasis. In addition, organ-dependent metabolic adaptations of TRMs appear to be fundamentally distinct in homeostasis and in response to a challenge, such as infection or injury. Moreover, TRM function becomes aberrant with advancing age, contributing to inflammaging and organ deterioration, and a metabolic imbalance may underlie TRM immunosenescence. Here, we outline current understanding of the particular metabolic states of TRMs across organs and the relevance for their function. Moreover, we discuss the concomitant aging-related decline in metabolic plasticity and functions of TRMs, highlighting potential novel therapeutic avenues to promote healthy aging.