{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:04:35Z","timestamp":1789646675622,"version":"4.0.0"},"reference-count":37,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-052"],"award-info":[{"award-number":["2021-I2M-1-052"]}]},{"DOI":"10.13039\/501100019018","name":"CAMS Plastic Surgery Hospital Institutional Fund","doi-asserted-by":"publisher","award":["YSZ2024CG002"],"award-info":[{"award-number":["YSZ2024CG002"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"award":["YSZ2024CG002"],"award-info":[{"award-number":["YSZ2024CG002"]}],"id":[{"id":"https:\/\/ror.org\/00fk0yb75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Skeletal muscle ageing is accompanied by impaired regeneration and remodelling of the multicellular niche, yet how age-related immune changes relate to altered muscle stem cell (MuSC) states in humans remains unclear. Here, we integrated bulk RNA-sequencing, scRNA-seq and an independent older adult cohort analysis to characterize age-associated changes in human skeletal muscle and identify candidate macrophage\u2013MuSC signalling interactions. Bulk transcriptomic analysis revealed inflammatory activation, reduced mitochondrial and metabolic programmes, and increased macrophage-associated signatures in aged muscle. Single-cell analysis resolved distinct myeloid and MuSC states. Among aged myeloid populations, inflammatory macrophages exhibited the highest SenMayo score, whereas donor-level pseudobulk analysis identified age-related early-primed MuSCs (epMuSC) remodelling involving inflammatory, interferon-related, and extracellular matrix-associated programmes. Ligand\u2013target modelling prioritized inhibin subunit beta A (INHBA)\/Activin A as a candidate signal linking inflammatory macrophages to the aged epMuSC programme. This prediction was further supported by an independent older adult human muscle scRNA-seq cohort showing concordant INHBA expression in inflammatory macrophages and Activin receptor expression in epMuSCs. In primary human MuSCs, Activin A induced Activin-responsive genes and suppressed myogenic regulators, and these effects were attenuated by SB431542, a small-molecule inhibitor of ALK4\/5\/7 signalling. Together, these findings support a candidate INHBA-associated, cell state-resolved communication framework between inflammatory macrophages and epMuSC remodelling in aged human muscle, providing a potential link between immune remodelling and altered regenerative cell states.<\/jats:p>","DOI":"10.3390\/ijms27188283","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:41:35Z","timestamp":1789645295000},"page":"8283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Transcriptomic Analysis Identifies a Candidate INHBA\/Activin A-Associated Macrophage\u2013MuSC Communication Axis in Human Skeletal Muscle Ageing"],"prefix":"10.3390","volume":"27","author":[{"given":"Xuanchen","family":"Liu","sequence":"first","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehui","family":"Li","sequence":"additional","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuo","family":"Si","sequence":"additional","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningbei","family":"Yin","sequence":"additional","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1042\/CS20230319","article-title":"Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men","volume":"137","author":"Granic","year":"2023","journal-title":"Clin. 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