2025/09/02 by Elsie Gonzalez-Hurtado, Claire Leveau, Keyi Li +14 · 2 voices
Medicine · Neuroscience · #Adipokines, Inflammation, and Metabolic Diseases #Adipose Tissue and Metabolism #Neuroinflammation and Neurodegeneration Mechanisms
paper · pdf · doi:10.1038/s43587-025-00952-9
openalex publication_date 2025/09/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Age-related inflammation or ‘inflammaging’ increases disease burden and controls lifespan. Adipose tissue macrophages (ATMs) are critical regulators of inflammaging; however, the mechanisms involved are not well understood in part because the molecular identities of niche-specific ATMs are unknown. Using intravascular labeling to exclude circulating myeloid cells followed by single-cell sequencing with orthogonal validation via multiparametric flow cytometry, we define sex-specific changes and diverse populations of resident ATMs through lifespan in mice. Aging led to depletion of vessel-associated macrophages, expansion of lipid-associated macrophages and emergence of a unique subset of CD38+ age-associated macrophages in visceral adipose tissue with inflammatory phenotype. Notably, CD169+CD11c− ATMs are enriched in a subpopulation of nerve-associated macrophages (NAMs) that declines with age. Depletion of CD169+ NAMs in aged mice increases inflammaging and impairs lipolysis suggesting catecholamine resistance in visceral adipose tissue. Our findings reveal NAMs are a specialized ATM subset that control adipose homeostasis and link inflammation to tissue dysfunction during aging. Gonzalez-Hurtado, Leveau and colleagues characterize adipose resident tissue macrophages across lifespan in mice, finding that nerve-associated macrophages, which mitigate inflammation and control lipolysis and catecholamine resistance, are lost during aging.