{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:54:52Z","timestamp":1790625292485,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Cell Biology","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Aged skeletal muscle has decreased ability to rebound from physiological stressors such as disuse atrophy. We previously observed that older adults during recovery following muscle disuse were characterized by rapid skeletal muscle immune cell expansion, cellular senescence and collagen deposition, responses that were biased toward older women. Here we used single-nucleus RNA sequencing and complementary\n                  <jats:italic>in vitro<\/jats:italic>\n                  muscle primary cell experiments in young (YF; 22\u00b13y; n=8) and older females (OF; 66\u00b15y; n=9) to investigate age-mediated cellular function and intercellular communication during recovery from disuse atrophy. Compared with YF, OF exhibited a markedly greater transcriptional response at 7d-recovery (YF: 1,548 DEGs, OF: 7,999 DEGs), driven primarily by slow- (YF: 96 DEGs, OF: 984 DEGs) and fast-twitch myonuclei (YF: 194 DEGs, OF: 1,234 DEGs), satellite cells (YF: 548 DEGs, OF: 2,784 DEGs) and FAPs (YF: 326 DEGs, OF: 2,102 DEGs). Satellite cells from OF demonstrated collagen signatures including elevated THBS1 expression and enrichment of TGF-\u03b2 signaling. Concurrently, OF FAPs exhibited increased expression of fibroblast activation marker ADAMTS14. Furthermore, NicheNet analyses unmasked altered FAP-satellite cell communication in OF. Complementary\n                  <jats:italic>In vitro<\/jats:italic>\n                  experiments revealed that myogenic progenitor cells collected at 7d-recovery from OF (vs YF) donors displayed impaired myogenic differentiation and a cellular senescence-associated phenotype, while fibroblasts exhibited greater myofibroblast-like activation. Conditioned media derived from OF fibroblasts at 7d-recovery further increased cellular senescence and impaired myogenic potential (vs YF fibroblast conditioned media). Collectively, these findings suggest that recovery from disuse atrophy in older females is characterized by altered FAP-satellite cell communication and intrinsic function which may contribute to poor muscle remodeling.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>GRAPHICAL ABSTRACT<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:label>Abstract Figure Legend<\/jats:label>\n                    <jats:caption>\n                      <jats:p>During re-ambulation following 14 days of unilateral limb immobilization, fibroblasts from older females (vs young females) exhibited an elevated activated myofibroblast-like phenotype. These changes were accompanied by altered fibro-adipogenic progenitor-satellite cell communication. Secretome derived from 7d-recovery fibroblasts increased cellular senescence and impaired myotube formation from older female donors. Collectively, these findings suggest that aging promotes a maladaptive fibrogenic secretory profile that impairs myogenic function and skeletal muscle remodeling following disuse atrophy.<\/jats:p>\n                    <\/jats:caption>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"753766v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.23.753766","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:20:11Z","timestamp":1790256011000},"source":"Crossref","is-referenced-by-count":0,"title":["Disrupted FAP-satellite cell communication contribute to maladaptive muscle remodeling in older women"],"prefix":"10.64898","author":[{"given":"Chad M.","family":"Skiles","sequence":"first","affiliation":[{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary J.","family":"Fennel","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul-Emile","family":"Bourrant","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena M.","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Keeble","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology, University of Kentucky, Lexington, KY, USA"},{"name":"Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Fry","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology, University of Kentucky, Lexington, KY, USA"},{"name":"Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-8890","authenticated-orcid":false,"given":"Micah J.","family":"Drummond","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA"},{"name":"Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA"},{"name":"Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092811551323000_2026.09.23.753766v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00426.2019.-We"},{"key":"2026092811551323000_2026.09.23.753766v1.2","doi-asserted-by":"crossref","unstructured":"Montenegro, C.F. , Skiles, C. , Kuszmaul, D.J. , Gouw, A. , Minchev, K. , Chambers, T.L. , Raue, U. , Trappe, T. , and Trappe, S . 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