Keep your macrophages fit for healthy aging

Jan Van Den Bossche,Pieter J.M Leenen

doi:10.1016/j.cmet.2021.02.004

Abstract

As age is the greatest risk factor for the development of most prevalent chronic diseases, there is an enormous interest in understanding the process of aging, with the hope of delaying or preventing age-related comorbidities. Along these lines, a recent study by Minhas etal. (2021) describes how aged macrophages downregulate glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), inducing an energy-deficient state that compromises macrophage function and supports maladaptive inflammation that together cause brain dysfunction.

Highlights

As age is the greatest risk factor for the development of most prevalent chronic diseases, there is an enormous interest in understanding the process of aging, with the hope of delaying or preventing age-related comorbidities
Recent work in the immunometabolism field highlights the critical role of cellular metabolism in regulating macrophage functions and disease progression (Russell et al, 2019)
Minhas et al started their study with the observation that synthesis of the lipid mediator prostaglandin E2 (PGE2) by cyclooxygenase-2 (COX-2) was increased in macrophages of both aged humans and mice (Minhas et al, 2021)

Summary

Keep your macrophages fit for healthy aging

As age is the greatest risk factor for the development of most prevalent chronic diseases, there is an enormous interest in understanding the process of aging, with the hope of delaying or preventing age-related comorbidities. Genetic or pharmacological inhibition of EP2 in mouse and human macrophages reduced glycogen synthesis and promoted the flux of glucose into glycolysis and TCA cycle to fuel mitochondrial respiration This beneficial effect of EP2 blockade on bioenergetics was GYS1 dependent and increased phagocytic activity of macrophages. Future studies should clarify which immune factors outside the brain are responsible for the observed effects of peripheral EP2 blockade on microglia and cognitive function This new study makes it tempting to speculate that inflammaging-associated macrophage dysfunction and cognitive decline are not necessarily permanent and might be reversed by targeting inflammatory signaling downstream of the myeloid receptor EP2. 468 Cell Metabolism 33, March 2, 2021 a 2021 Elsevier Inc

Gene c knockdown

Mitochondrial dysfunction defines T cell exhaustion