Integrated single-cell RNA sequencing across multiple organs of young and aged mice shows that aging reshapes neutrophil differentiation from the bone marrow outward, producing organ-specific shifts in neutrophil abundance and state. An age-enriched neutrophil population defined by IL-6-related transcriptional programs was identified, and conditioned media from aged or IL-6-stimulated neutrophils increased inflammatory and senescence-associated responses in vascular smooth muscle and hepatocyte-derived cells. The work positions neutrophil state, rather than neutrophil number alone, as a measurable contributor to age-related tissue inflammation.
Key Points
- Aging shifts neutrophil states differently across individual organs
- IL-6-linked neutrophil subset nominated as driver of tissue senescence
- Aged bone marrow progenitors show enhanced myeloid priming
Longevity Analysis
Chronic low-grade inflammation in older tissue is often treated as a diffuse background condition; here it traces to identifiable immune cell states originating in marrow progenitor bias and propagating outward to vessel walls and liver cells. That gives a concrete upstream target — the signaling environment that instructs neutrophil production — rather than downstream suppression of inflammation after tissue damage has begun. Interventions that reduce inflammatory load and support marrow-level renewal gain a mechanistic rationale, and IL-6 signaling emerges as a candidate marker for tracking whether those interventions are changing anything measurable.
Original published by Wiley Aging Cell, by Yuman Wang, Teding Chang, Yangguang Fu, Guangyu Liang, Huicheng Liu, Le Zhang, Jinhua Yan, Man Liu, Anding Liu, Cuntai Zhang .