Researchers at Yale identified a population of nerve-associated macrophages (NAMs) in visceral fat tissue that decline with aging. Using single-cell RNA sequencing and intravascular labeling to distinguish true tissue-resident immune cells from circulating ones, the team mapped 13 distinct macrophage subsets across the lifespan of male and female mice. With age, NAMs—marked by CD169 expression—were depleted, while inflammatory and lipid-associated macrophage subsets expanded. Depletion of CD169+ NAMs in aged mice worsened inflammation and impaired lipolysis, suggesting these cells normally protect fat tissue from catecholamine resistance. This work establishes NAMs as critical regulators of adipose homeostasis and links their loss to the chronic low-grade inflammation characteristic of aging.
