Aging remodels mouse neutrophils across organs to drive inflammatory and senescence responses
Single-cell profiling reveals distinct neutrophil subsets that promote senescence in vascular and liver cells while altering bone marrow progenitor states.
In mice, aging alters neutrophil abundance and cellular states across multiple organs, according to single-cell RNA sequencing analyses. Researchers mapped tissue-specific changes by comparing young and aged animals, identifying neutrophil subsets with elevated inflammatory, complement, oxidative stress, and IL-6 signaling signatures. These aged immune cells also influenced surrounding tissues. In cell culture assays, exposure to conditioned media from aged mouse neutrophils or IL-6-stimulated neutrophil-like cells induced inflammatory and senescence-associated responses in vascular smooth muscle cells and hepatocyte-derived cells. In the bone marrow, single-cell profiling showed age-related shifts in progenitor populations, including the expansion of an HPC11 progenitor subset marked by heightened myeloid priming. Computational perturbation analyses further nominated candidate regulators of these progenitor programs.
Why it matters
The findings establish a multi-organ atlas of neutrophil aging, highlighting how specific innate immune subsets directly promote tissue inflammation and cellular senescence across the body.
Caveats
The findings are based entirely on mouse datasets and in vitro cell culture, meaning these neutrophil dynamics require direct validation in human aging.
- Cellular senescence
- Chronic inflammation
- Stem cell exhaustion
- Complement system
- Oxidative stress and ROS signalling
- Mus musculus
The paper
Single-Cell Mapping Identifies Aging-Associated Neutrophil Remodeling Across Multiple Organs
Wang Y, Chang T, Fu Y et al.
Aging Cell · 30 Sep 2026