Macrophage Immunometabolism and Inflammaging: Roles of Mitochondrial Dysfunction, Cellular Senescence, CD38, and NAD

Aging is a complex process that involves dysfunction on multiple levels, all of which seem to converge on inflammation. Macrophages are intimately involved in initiating and resolving inflammation, and their dysregulation with age is a primary contributor to inflammaging(definition)-a state of chronic, low-grade inflammation that develops during aging. Among the age-related changes that occur to macrophages are a heightened state of basal inflammation and diminished or hyperactive inflammatory responses, which seem to be driven by metabolic-dependent epigenetic changes. In this review article we provide a brief overview of mitochondrial functions and age-related changes that occur to macrophages, with an emphasis on how the inflammaging environment, senescence(definition), and NAD decline can affect their metabolism, promote dysregulation, and contribute to inflammaging and age-related pathologies.