Macrophages, metabolites, and nucleosomes: Chromatin at the intersection between aging and inflammation

Abstract

Inflammation is the body’s means of defense against harmful stimuli, with the ultimate aim being to restore homeostasis. Controlled acute inflammation transiently activates an immune response and can be beneficial as protection against infection or injury. However, dysregulated inflammatory responses, including chronic inflammation, disrupt the immune system’s ability to maintain homeostatic balance, leading to increased susceptibility to infection, continuous tissue damage, and dysfunction. Aging is a risk factor for chronic inflammation; their coincidence is termed “inflammaging”. Metabolic disorders including obesity, neurodegenerative diseases, and atherosclerosis are often encountered in old age. Therefore, it is important to understand the mechanistic relationship between aging, chronic inflammation, and metabolism. It has been established that the expression of inflammatory mediators is transcriptionally and translationally regulated. In addition, the post-translational modification of the mediators plays a crucial role in the response to inflammatory signaling. Chromatin regulation responds to metabolic status and controls homeostasis. However, chromatin structure is also changed by aging. In this review, we discuss the functional contributions of chromatin regulation to inflammaging.