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.
International journal of molecular sciences · Liu X et al. · Paper published 17 Sep 2026
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.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
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 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Notable
- Evidence
- Humans
- Status
- Peer-reviewed
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