Activin A from inflammatory macrophages impairs stem cell regulation in aging human muscle
Researchers mapped signaling pathways between senescent-like immune cells and muscle stem cells across multiple human transcriptomic datasets.
In human skeletal muscle tissue and isolated cells, researchers integrated bulk and single-cell RNA sequencing to study immune and stem cell communication during aging. Bulk transcriptomics showed increased inflammation, reduced metabolic and mitochondrial programs, and elevated macrophage signatures in aged muscle. Single-cell analysis revealed that inflammatory macrophages had the highest SenMayo senescence scores, while early-primed muscle stem cells underwent remodeling linked to inflammation and the extracellular matrix. Ligand-target modeling and an independent older adult cohort prioritized macrophage-derived INHBA, also known as Activin A, which paired with Activin receptors on muscle stem cells. In primary human muscle stem cells, Activin A suppressed myogenic regulators, while the ALK4/5/7 inhibitor SB431542 attenuated these inhibitory effects.
Why it matters
The findings define a candidate communication route linking immune system alterations directly to disrupted regenerative stem cell programs in human muscle aging.
Caveats
The proposed macrophage-stem cell communication axis is based largely on computational modeling of observational transcriptomic data alongside in vitro cell cultures.
- Activin a
- SB-431542
- Altered intercellular communication
- Cellular senescence
- Chronic inflammation
- Mitochondrial dysfunction
- Stem cell exhaustion
- TGF-β signalling
- Type I interferon signalling
- ACVR1B
- INHBA
- SenMayo
The paper
Integrated Transcriptomic Analysis Identifies a Candidate INHBA/Activin A-Associated Macrophage-MuSC Communication Axis in Human Skeletal Muscle Ageing
Liu X, Li Z, Yuan Y et al.
International Journal of Molecular Sciences · 17 Sep 2026