A recent study using single-cell RNA sequencing of visceral white adipose tissue in mice aged 2 and 22 months revealed distinct macrophage clusters that vary significantly by sex and age, with some clusters being more prevalent in males or females.

Aging impacts macrophage populations differently in male and female mice; for instance, Cluster 0 decreases in aging males, while Cluster 5 decreases in females, and Cluster 13 increases only in females, with several clusters showing pro-inflammatory features.

Researchers have classified various macrophage subtypes in adipose tissue, including nerve-associated macrophages (NAMs), lipid-associated macrophages (LAMs), and vasculature-associated macrophages (VAMs), and studied how these populations change with age.

Adipose-derived NAMs are essential for maintaining nerve health and myelin around neuronal axons, and their depletion in young mice leads to disrupted catecholamine regulation and increased obesity risk.

Depleting NAMs in older mice results in heightened inflammation, highlighting their protective role diminishes with age but remains crucial for metabolic health.

The study underscores macrophage heterogeneity and its alterations during aging, suggesting potential targeted therapies such as reducing aging-associated macrophages to combat obesity and metabolic decline.

Aging-associated macrophages (AAMs), particularly Cluster 4, express pro-inflammatory markers and CD38, and their numbers increase with age in both sexes, contributing to cellular senescence.