Nature agingSep 2, 2025

Nerve-related immune cells regulate fat tissue balance throughout life and reduce inflammation with aging

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Nerve-associated adipose macrophages appear to help restrain aging-related visceral fat inflammation and lipolysis defects.

Evidence

This mouse lifespan study used intravascular labeling, single-cell sequencing, flow cytometry, and CD169 nerve-associated macrophage depletion to map resident and test aged visceral adipose function.

Caveat

The functional evidence comes from mouse CD169 nerve-associated macrophage depletion in visceral adipose tissue, so human relevance and other fat depots remain untested.

Simplified

Age-related inflammation or '' increases disease burden and controls lifespan. (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 CD38age-associated macrophages in visceral adipose tissue with inflammatory phenotype. Notably, CD169CD11cATMs are enriched in a subpopulation of nerve-associated macrophages (NAMs) that declines with age. Depletion of CD169NAMs in aged mice increases inflammaging and impairs lipolysis suggesting 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. + + -+

Key numbers

16-fold

Increase in Monocytes

Observed in aged -DTR mice after NAM depletion.

from 1% to nearly 20%

Expansion of AAMs

AAMs increased in aged male mice.

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Funding

Competing interests

0%of authors

0 of 17

authors report competing interests

17 report none

PubMed

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