{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:54:48Z","timestamp":1793346888047,"version":"4.5.0"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR070334"],"award-info":[{"award-number":["AR070334"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR070334"],"award-info":[{"award-number":["AR070334"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100032490","name":"Freedom Together Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032490","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG072874"],"award-info":[{"award-number":["AG072874"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1038\/s41590-026-02435-4","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:01:59Z","timestamp":1772553719000},"page":"543-555","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Piezo1-dependent activation of stromal cells ignites muscle inflammation in exercise and injury and is associated with inflammaging"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6655-1911","authenticated-orcid":false,"given":"P. Kent","family":"Langston","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree","family":"Vijaya Raghavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1172-6555","authenticated-orcid":false,"given":"Christophe","family":"Benoist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6110-4626","authenticated-orcid":false,"given":"Diane","family":"Mathis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"2435_CR1","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","volume":"25","author":"D Furman","year":"2019","unstructured":"Furman, D. et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 25, 1822\u20131832 (2019).","journal-title":"Nat. Med."},{"key":"2435_CR2","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1001\/jamainternmed.2015.0533","volume":"175","author":"H Arem","year":"2015","unstructured":"Arem, H. et al. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern. Med. 175, 959\u2013967 (2015).","journal-title":"JAMA Intern. Med."},{"key":"2435_CR3","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1016\/j.cell.2020.06.004","volume":"181","author":"JA Sanford","year":"2020","unstructured":"Sanford, J. A. et al. Molecular Transducers of Physical Activity Consortium (MoTrPAC): mapping the dynamic responses to exercise. Cell 181, 1464\u20131474 (2020).","journal-title":"Cell"},{"key":"2435_CR4","doi-asserted-by":"crossref","unstructured":"MoTrPAC Study Group, Lead Analysts & MoTrPAC Study Group Temporal dynamics of the multi-omic response to endurance exercise training. Nature 629, 174\u2013183 (2024).","DOI":"10.1038\/s41586-023-06877-w"},{"key":"2435_CR5","doi-asserted-by":"publisher","first-page":"eadi5377","DOI":"10.1126\/sciimmunol.adi5377","volume":"8","author":"PK Langston","year":"2023","unstructured":"Langston, P. K. et al. Regulatory T cells shield muscle mitochondria from interferon-\u03b3-mediated damage to promote the beneficial effects of exercise. Sci. Immunol. 8, eadi5377 (2023).","journal-title":"Sci. Immunol."},{"key":"2435_CR6","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.cmet.2024.04.001","volume":"36","author":"PK Langston","year":"2024","unstructured":"Langston, P. K. & Mathis, D. Immunological regulation of skeletal muscle adaptation to exercise. Cell Metab. 36, 1175\u20131183 (2024).","journal-title":"Cell Metab"},{"key":"2435_CR7","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/j.cmet.2023.08.010","volume":"35","author":"M Becker","year":"2023","unstructured":"Becker, M. et al. Regulatory T cells require IL6 receptor \u03b1 signaling to control skeletal muscle function and regeneration. Cell Metab. 35, 1736\u20131751 (2023).","journal-title":"Cell Metab"},{"key":"2435_CR8","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.cmet.2024.12.011","volume":"37","author":"T Van der Stede","year":"2025","unstructured":"Van der Stede, T. et al. Cellular deconstruction of the human skeletal muscle microenvironment identifies an exercise-induced histaminergic crosstalk. Cell Metab. 37, 842\u2013856 (2025).","journal-title":"Cell Metab."},{"key":"2435_CR9","doi-asserted-by":"publisher","first-page":"eabo3192","DOI":"10.1126\/sciadv.abo3192","volume":"8","author":"NJ Pillon","year":"2022","unstructured":"Pillon, N. J. et al. Distinctive exercise-induced inflammatory response and exerkine induction in skeletal muscle of people with type 2 diabetes. Sci. Adv. 8, eabo3192 (2022).","journal-title":"Sci. Adv."},{"key":"2435_CR10","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.stem.2023.12.011","volume":"31","author":"X Kang","year":"2024","unstructured":"Kang, X. et al. Exercise-induced musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis. Cell Stem Cell 31, 212\u2013226 (2024).","journal-title":"Cell Stem Cell"},{"key":"2435_CR11","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.cmet.2023.04.011","volume":"35","author":"W Wei","year":"2023","unstructured":"Wei, W. et al. Organism-wide, cell-type-specific secretome mapping of exercise training in mice. Cell Metab. 35, 1261\u20131279 (2023).","journal-title":"Cell Metab."},{"key":"2435_CR12","doi-asserted-by":"publisher","first-page":"eaat3987","DOI":"10.1126\/science.aat3987","volume":"368","author":"NH Knudsen","year":"2020","unstructured":"Knudsen, N. H. et al. Interleukin-13 drives metabolic conditioning of muscle to endurance exercise. Science 368, eaat3987 (2020).","journal-title":"Science"},{"key":"2435_CR13","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.cmet.2022.09.004","volume":"34","author":"J Yang","year":"2022","unstructured":"Yang, J. et al. Single-cell dissection of the obesity\u2013exercise axis in adipose\u2013muscle tissues implies a critical role for mesenchymal stem cells. Cell Metab. 34, 1578\u20131593 (2022).","journal-title":"Cell Metab."},{"key":"2435_CR14","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.stem.2023.03.016","volume":"30","author":"L Liu","year":"2023","unstructured":"Liu, L. et al. Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging. Cell Stem Cell 30, 689\u2013705 (2023).","journal-title":"Cell Stem Cell"},{"key":"2435_CR15","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/ncb2015","volume":"12","author":"AW Joe","year":"2010","unstructured":"Joe, A. W. et al. Muscle injury activates resident fibro\/adipogenic progenitors that facilitate myogenesis. Nat. Cell Biol. 12, 153\u2013163 (2010).","journal-title":"Nat. Cell Biol."},{"key":"2435_CR16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/ncb2014","volume":"12","author":"A Uezumi","year":"2010","unstructured":"Uezumi, A. et al. Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat. Cell Biol. 12, 143\u2013152 (2010).","journal-title":"Nat. Cell Biol."},{"key":"2435_CR17","doi-asserted-by":"publisher","first-page":"3654","DOI":"10.1242\/jcs.086629","volume":"124","author":"A Uezumi","year":"2011","unstructured":"Uezumi, A. et al. Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. J. Cell Sci. 124, 3654\u20133664 (2011).","journal-title":"J. Cell Sci."},{"key":"2435_CR18","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1016\/j.celrep.2019.04.074","volume":"27","author":"MN Wosczyna","year":"2019","unstructured":"Wosczyna, M. N. et al. Mesenchymal stromal cells are required for regeneration and homeostatic maintenance of skeletal muscle. Cell Rep. 27, 2029\u20132035 (2019).","journal-title":"Cell Rep."},{"key":"2435_CR19","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1038\/s41590-023-01669-w","volume":"24","author":"OK Yaghi","year":"2023","unstructured":"Yaghi, O. K. et al. A discrete \u2018early-responder\u2019 stromal-cell subtype orchestrates immunocyte recruitment to injured tissue. Nat. Immunol. 24, 2053\u20132067 (2023).","journal-title":"Nat. Immunol."},{"key":"2435_CR20","doi-asserted-by":"publisher","first-page":"e29760","DOI":"10.1371\/journal.pone.0029760","volume":"7","author":"MC Valero","year":"2012","unstructured":"Valero, M. C. et al. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle. PLoS ONE 7, e29760 (2012).","journal-title":"PLoS ONE"},{"key":"2435_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14734-x","volume":"11","author":"Y Saito","year":"2020","unstructured":"Saito, Y. et al. Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors. Nat. Commun. 11, 889 (2020).","journal-title":"Nat. Commun."},{"key":"2435_CR22","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1002\/path.1415","volume":"200","author":"R Chiquet-Ehrismann","year":"2003","unstructured":"Chiquet-Ehrismann, R. & Chiquet, M. Tenascins: regulation and putative functions during pathological stress. J. Pathol. 200, 488\u2013499 (2003).","journal-title":"J. Pathol."},{"key":"2435_CR23","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1007\/s00018-011-0783-6","volume":"68","author":"KS Midwood","year":"2011","unstructured":"Midwood, K. S., Hussenet, T., Langlois, B. & Orend, G. Advances in tenascin-C biology. Cell. Mol. Life Sci. 68, 3175\u20133199 (2011).","journal-title":"Cell. Mol. Life Sci."},{"key":"2435_CR24","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/nm.1987","volume":"15","author":"K Midwood","year":"2009","unstructured":"Midwood, K. et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat. Med. 15, 774\u2013780 (2009).","journal-title":"Nat. Med."},{"key":"2435_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01718-7","volume":"8","author":"L Zuliani-Alvarez","year":"2017","unstructured":"Zuliani-Alvarez, L. et al. Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nat. Commun. 8, 1595 (2017).","journal-title":"Nat. Commun."},{"key":"2435_CR26","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1369\/0022155418757443","volume":"66","author":"AM Marzeda","year":"2018","unstructured":"Marzeda, A. M. & Midwood, K. S. Internal affairs: tenascin-C as a clinically relevant, endogenous driver of innate immunity. J. Histochem. Cytochem. 66, 289\u2013304 (2018).","journal-title":"J. Histochem. Cytochem."},{"key":"2435_CR27","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.stem.2018.12.014","volume":"24","author":"L Lukjanenko","year":"2019","unstructured":"Lukjanenko, L. et al. Aging disrupts muscle stem cell function by impairing matricellular WISP1 secretion from fibro-adipogenic progenitors. Cell Stem Cell 24, 433\u2013446 (2019).","journal-title":"Cell Stem Cell"},{"key":"2435_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13869-w","volume":"11","author":"NJ Pillon","year":"2020","unstructured":"Pillon, N. J. et al. Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity. Nat. Commun. 11, 470 (2020).","journal-title":"Nat. Commun."},{"key":"2435_CR29","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1038\/s42255-023-00891-y","volume":"5","author":"R Furrer","year":"2023","unstructured":"Furrer, R. et al. Molecular control of endurance training adaptation in male mouse skeletal muscle. Nat. Metab. 5, 2020\u20132035 (2023).","journal-title":"Nat. Metab."},{"key":"2435_CR30","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1152\/japplphysiol.01295.2009","volume":"108","author":"JA Timmons","year":"2010","unstructured":"Timmons, J. A. et al. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J. Appl. Physiol. 108, 1487\u20131496 (2010).","journal-title":"J. Appl. Physiol."},{"key":"2435_CR31","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1111\/j.1460-9568.2004.03720.x","volume":"20","author":"S Vaynman","year":"2004","unstructured":"Vaynman, S., Ying, Z. & Gomez-Pinilla, F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur. J. Neurosci. 20, 2580\u20132590 (2004).","journal-title":"Eur. J. Neurosci."},{"key":"2435_CR32","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jpsychires.2014.10.003","volume":"60","author":"KL Szuhany","year":"2015","unstructured":"Szuhany, K. L., Bugatti, M. & Otto, M. W. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res. 60, 56\u201364 (2015).","journal-title":"J. Psychiatr. Res."},{"key":"2435_CR33","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","volume":"126","author":"AJ Engler","year":"2006","unstructured":"Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677\u2013689 (2006).","journal-title":"Cell"},{"key":"2435_CR34","doi-asserted-by":"publisher","first-page":"3583","DOI":"10.1242\/jcs.113.20.3583","volume":"113","author":"M Fl\u00fcck","year":"2000","unstructured":"Fl\u00fcck, M., Tunc-Civelek, V. & Chiquet, M. Rapid and reciprocal regulation of tenascin-C and tenascin-Y expression by loading of skeletal muscle. J. Cell Sci. 113, 3583\u20133591 (2000).","journal-title":"J. Cell Sci."},{"key":"2435_CR35","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0945-053X(03)00004-0","volume":"22","author":"M Chiquet","year":"2003","unstructured":"Chiquet, M., Renedo, A. S., Huber, F. & Fluck, M. How do fibroblasts translate mechanical signals into changes in extracellular matrix production?. Matrix Biol. 22, 73\u201380 (2003).","journal-title":"Matrix Biol."},{"key":"2435_CR36","doi-asserted-by":"crossref","unstructured":"Tse, J.R. & Engler, A.J. Preparation of hydrogel substrates with tunable mechanical properties. Curr. Protoc. Cell Biol. Chapter 10, Unit 10.16 (2010).","DOI":"10.1002\/0471143030.cb1016s47"},{"key":"2435_CR37","doi-asserted-by":"publisher","first-page":"eadk6906","DOI":"10.1126\/sciadv.adk6906","volume":"10","author":"ML Meizlish","year":"2024","unstructured":"Meizlish, M. L. et al. Mechanosensing regulates tissue repair program in macrophages. Sci. Adv. 10, eadk6906 (2024).","journal-title":"Sci. Adv."},{"key":"2435_CR38","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41577-022-00761-w","volume":"23","author":"H Du","year":"2023","unstructured":"Du, H. et al. Tuning immunity through tissue mechanotransduction. Nat. Rev. Immunol. 23, 174\u2013188 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"2435_CR39","doi-asserted-by":"publisher","first-page":"e49631","DOI":"10.7554\/eLife.49631","volume":"8","author":"X Li","year":"2019","unstructured":"Li, X. et al. Stimulation of Piezo1 by mechanical signals promotes bone anabolism. eLife 8, e49631 (2019).","journal-title":"eLife"},{"key":"2435_CR40","doi-asserted-by":"publisher","first-page":"e52779","DOI":"10.7554\/eLife.52779","volume":"9","author":"T Zhou","year":"2020","unstructured":"Zhou, T. et al. Piezo1\/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT\u2013YAP1\u2013\u03b2-catenin. eLife 9, e52779 (2020).","journal-title":"eLife"},{"key":"2435_CR41","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/s41586-021-03298-5","volume":"591","author":"B Shen","year":"2021","unstructured":"Shen, B. et al. A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Nature 591, 438\u2013444 (2021).","journal-title":"Nature"},{"key":"2435_CR42","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1085\/jgp.115.5.583","volume":"115","author":"TM Suchyna","year":"2000","unstructured":"Suchyna, T. M. et al. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J. Gen. Physiol. 115, 583\u2013598 (2000).","journal-title":"J. Gen. Physiol."},{"key":"2435_CR43","doi-asserted-by":"publisher","first-page":"6295","DOI":"10.1021\/bi200770q","volume":"50","author":"C Bae","year":"2011","unstructured":"Bae, C., Sachs, F. & Gottlieb, P. A. The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry 50, 6295\u20136300 (2011).","journal-title":"Biochemistry"},{"key":"2435_CR44","doi-asserted-by":"publisher","first-page":"e07369","DOI":"10.7554\/eLife.07369","volume":"4","author":"R Syeda","year":"2015","unstructured":"Syeda, R. et al. Chemical activation of the mechanotransduction channel Piezo1. eLife 4, e07369 (2015).","journal-title":"eLife"},{"key":"2435_CR45","doi-asserted-by":"publisher","first-page":"17395","DOI":"10.1074\/jbc.RA119.009167","volume":"294","author":"NM Blythe","year":"2019","unstructured":"Blythe, N. M. et al. Mechanically activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase activity and interleukin-6 secretion. J. Biol. Chem. 294, 17395\u201317408 (2019).","journal-title":"J. Biol. Chem."},{"key":"2435_CR46","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s001090050063","volume":"74","author":"AJ Whitmarsh","year":"1996","unstructured":"Whitmarsh, A. J. & Davis, R. J. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J. Mol. Med. 74, 589\u2013607 (1996).","journal-title":"J. Mol. Med."},{"key":"2435_CR47","doi-asserted-by":"publisher","first-page":"4969","DOI":"10.1093\/emboj\/18.18.4969","volume":"18","author":"R Winzen","year":"1999","unstructured":"Winzen, R. et al. The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. 18, 4969\u20134980 (1999).","journal-title":"EMBO J."},{"key":"2435_CR48","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0945-053X(99)00039-6","volume":"18","author":"M Chiquet","year":"1999","unstructured":"Chiquet, M. Regulation of extracellular matrix gene expression by mechanical stress. Matrix Biol. 18, 417\u2013426 (1999).","journal-title":"Matrix Biol."},{"key":"2435_CR49","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1152\/physrev.00031.2003","volume":"84","author":"M Kjaer","year":"2004","unstructured":"Kjaer, M. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol. Rev. 84, 649\u2013698 (2004).","journal-title":"Physiol. Rev."},{"key":"2435_CR50","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.immuni.2023.01.033","volume":"56","author":"BS Hanna","year":"2023","unstructured":"Hanna, B. S. et al. The gut microbiota promotes distal tissue regeneration via ROR\u03b3+ regulatory T cell emissaries. Immunity 56, 829\u2013846 (2023).","journal-title":"Immunity"},{"key":"2435_CR51","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/nri.2016.150","volume":"17","author":"JG Tidball","year":"2017","unstructured":"Tidball, J. G. Regulation of muscle growth and regeneration by the immune system. Nat. Rev. Immunol. 17, 165\u2013178 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"2435_CR52","first-page":"677","volume":"139","author":"MA Alnaqeeb","year":"1984","unstructured":"Alnaqeeb, M. A., Al Zaid, N. S. & Goldspink, G. Connective tissue changes and physical properties of developing and ageing skeletal muscle. J. Anat. 139, 677\u2013689 (1984).","journal-title":"J. Anat."},{"key":"2435_CR53","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1152\/japplphysiol.00256.2014","volume":"117","author":"LK Wood","year":"2014","unstructured":"Wood, L. K. et al. Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice. J Appl. Physiol. 117, 363\u2013369 (2014).","journal-title":"J Appl. Physiol."},{"key":"2435_CR54","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1111\/acel.12578","volume":"16","author":"KM Stearns-Reider","year":"2017","unstructured":"Stearns-Reider, K. M. et al. Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion. Aging Cell 16, 518\u2013528 (2017).","journal-title":"Aging Cell"},{"key":"2435_CR55","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1111\/acel.12350","volume":"14","author":"Y Wang","year":"2015","unstructured":"Wang, Y., Wehling-Henricks, M., Samengo, G. & Tidball, J. G. Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by muscle-derived nitric oxide. Aging Cell 14, 678\u2013688 (2015).","journal-title":"Aging Cell"},{"key":"2435_CR56","doi-asserted-by":"publisher","first-page":"e13690","DOI":"10.1111\/acel.13690","volume":"21","author":"Y Wang","year":"2022","unstructured":"Wang, Y. et al. Myeloid cell-specific mutation of Spi1 selectively reduces M2-biased macrophage numbers in skeletal muscle, reduces age-related muscle fibrosis and prevents sarcopenia. Aging Cell 21, e13690 (2022).","journal-title":"Aging Cell"},{"key":"2435_CR57","doi-asserted-by":"publisher","first-page":"zqab028","DOI":"10.1093\/function\/zqab028","volume":"2","author":"CB Abbott","year":"2021","unstructured":"Abbott, C. B. et al. A novel stable isotope approach demonstrates surprising degree of age-related decline in skeletal muscle collagen proteostasis. Function 2, zqab028 (2021).","journal-title":"Function"},{"key":"2435_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00429-3","volume":"8","author":"B Rode","year":"2017","unstructured":"Rode, B. et al. Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance. Nat. Commun. 8, 350 (2017).","journal-title":"Nat. Commun."},{"key":"2435_CR59","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1016\/j.cell.2025.02.031","volume":"188","author":"Z Xie","year":"2025","unstructured":"Xie, Z. et al. Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force. Cell 188, 2417\u20132432 (2025).","journal-title":"Cell"},{"key":"2435_CR60","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41586-019-1485-8","volume":"573","author":"AG Solis","year":"2019","unstructured":"Solis, A. G. et al. Mechanosensation of cyclical force by Piezo1 is essential for innate immunity. Nature 573, 69\u201374 (2019).","journal-title":"Nature"},{"key":"2435_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23482-5","volume":"12","author":"H Atcha","year":"2021","unstructured":"Atcha, H. et al. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat. Commun. 12, 3256 (2021).","journal-title":"Nat. Commun."},{"key":"2435_CR62","doi-asserted-by":"publisher","first-page":"108609","DOI":"10.1016\/j.celrep.2020.108609","volume":"34","author":"M Chakraborty","year":"2021","unstructured":"Chakraborty, M. et al. Mechanical stiffness controls dendritic cell metabolism and function. Cell Rep. 34, 108609 (2021).","journal-title":"Cell Rep."},{"key":"2435_CR63","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1193270","volume":"330","author":"B Coste","year":"2010","unstructured":"Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55\u201360 (2010).","journal-title":"Science"},{"key":"2435_CR64","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.cyto.2009.08.002","volume":"48","author":"G Huang","year":"2009","unstructured":"Huang, G., Shi, L. Z. & Chi, H. Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination. Cytokine 48, 161\u2013169 (2009).","journal-title":"Cytokine"},{"key":"2435_CR65","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.bbabio.2009.01.005","volume":"1787","author":"RM Denton","year":"2009","unstructured":"Denton, R. M. Regulation of mitochondrial dehydrogenases by calcium ions. Biochim. Biophys. Acta 1787, 1309\u20131316 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"2435_CR66","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1038\/s41590-019-0453-7","volume":"20","author":"PK Langston","year":"2019","unstructured":"Langston, P. K. et al. Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses. Nat. Immunol. 20, 1186\u20131195 (2019).","journal-title":"Nat. Immunol."},{"key":"2435_CR67","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1126\/science.abi5200","volume":"374","author":"R Medzhitov","year":"2021","unstructured":"Medzhitov, R. The spectrum of inflammatory responses. Science 374, 1070\u20131075 (2021).","journal-title":"Science"},{"key":"2435_CR68","doi-asserted-by":"publisher","first-page":"eabe4501","DOI":"10.1126\/sciadv.abe4501","volume":"7","author":"JS Silver","year":"2021","unstructured":"Silver, J. S. et al. Injury-mediated stiffening persistently activates muscle stem cells through YAP and TAZ mechanotransduction. Sci. Adv. 7, eabe4501 (2021).","journal-title":"Sci. Adv."},{"key":"2435_CR69","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1152\/jappl.1998.85.3.1011","volume":"85","author":"LE Gosselin","year":"1998","unstructured":"Gosselin, L. E. et al. Effect of exercise training on passive stiffness in locomotor skeletal muscle: role of extracellular matrix. J. Appl. Physiol. 85, 1011\u20131016 (1998).","journal-title":"J. Appl. Physiol."},{"key":"2435_CR70","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.immuni.2016.01.009","volume":"44","author":"W Kuswanto","year":"2016","unstructured":"Kuswanto, W. et al. Poor repair of skeletal muscle in aging mice reflects a defect in local, interleukin-33-dependent accumulation of regulatory T cells. Immunity 44, 355\u2013367 (2016).","journal-title":"Immunity"},{"key":"2435_CR71","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/s41586-022-05535-x","volume":"613","author":"V Moiseeva","year":"2023","unstructured":"Moiseeva, V. et al. Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration. Nature 613, 169\u2013178 (2023).","journal-title":"Nature"},{"key":"2435_CR72","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/s42003-022-04088-z","volume":"5","author":"A Lovric","year":"2022","unstructured":"Lovric, A. et al. Single-cell sequencing deconvolutes cellular responses to exercise in human skeletal muscle. Commun. Biol. 5, 1121 (2022).","journal-title":"Commun. Biol"},{"key":"2435_CR73","doi-asserted-by":"publisher","first-page":"e07370","DOI":"10.7554\/eLife.07370","volume":"4","author":"SM Cahalan","year":"2015","unstructured":"Cahalan, S. M. et al. Piezo1 links mechanical forces to red blood cell volume. eLife 4, e07370 (2015).","journal-title":"eLife"},{"key":"2435_CR74","doi-asserted-by":"publisher","first-page":"30014","DOI":"10.1074\/jbc.M704817200","volume":"282","author":"C Handschin","year":"2007","unstructured":"Handschin, C. et al. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1\u03b1 muscle-specific knock-out animals. J. Biol. Chem. 282, 30014\u201330021 (2007).","journal-title":"J. Biol. Chem."},{"key":"2435_CR75","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1038\/nprot.2015.110","volume":"10","author":"L Liu","year":"2015","unstructured":"Liu, L., Cheung, T. H., Charville, G. W. & Rando, T. A. Isolation of skeletal muscle stem cells by fluorescence-activated cell sorting. Nat. Protoc. 10, 1612\u20131624 (2015).","journal-title":"Nat. Protoc."},{"key":"2435_CR76","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.4049\/jimmunol.1400391","volume":"195","author":"PK Langston","year":"2015","unstructured":"Langston, P. K. et al. Au-ACRAMTU-PEt3 alters redox balance to inhibit T cell proliferation and function. J. Immunol. 195, 1984\u20131994 (2015).","journal-title":"J. Immunol."},{"key":"2435_CR77","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nprot.2014.006","volume":"9","author":"S Picelli","year":"2014","unstructured":"Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171\u2013181 (2014).","journal-title":"Nat. Protoc."},{"key":"2435_CR78","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"2435_CR79","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1093\/bioinformatics\/bty895","volume":"35","author":"A Zhu","year":"2019","unstructured":"Zhu, A., Ibrahim, J. G. & Love, M. I. Heavy-tailed prior distributions for sequence count data: removing the noise and preserving large differences. Bioinformatics 35, 2084\u20132092 (2019).","journal-title":"Bioinformatics"},{"key":"2435_CR80","doi-asserted-by":"publisher","unstructured":"Korotkevich, G. et al. Fast gene set enrichment analysis. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/060012 (2021).","DOI":"10.1101\/060012"},{"key":"2435_CR81","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).","journal-title":"Nat. Commun."},{"key":"2435_CR82","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72564-9","volume":"10","author":"A Cal\u00f2","year":"2020","unstructured":"Cal\u00f2, A. et al. Spatial mapping of the collagen distribution in human and mouse tissues by force volume atomic force microscopy. Sci. Rep. 10, 15664 (2020).","journal-title":"Sci. Rep."},{"key":"2435_CR83","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1039\/c5ib00040h","volume":"7","author":"I Acerbi","year":"2015","unstructured":"Acerbi, I. et al. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr. Biol. 7, 1120\u20131134 (2015).","journal-title":"Integr. Biol."},{"key":"2435_CR84","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.jbiomech.2010.12.018","volume":"44","author":"J Peloquin","year":"2011","unstructured":"Peloquin, J., Huynh, J., Williams, R. M. & Reinhart-King, C. A. Indentation measurements of the subendothelial matrix in bovine carotid arteries. J. Biomech. 44, 815\u2013821 (2011).","journal-title":"J. Biomech."},{"key":"2435_CR85","doi-asserted-by":"publisher","first-page":"100167","DOI":"10.1016\/j.xpro.2020.100167","volume":"1","author":"Y Shen","year":"2020","unstructured":"Shen, Y., Schmidt, T. & Diz-Munoz, A. Protocol on tissue preparation and measurement of tumor stiffness in primary and metastatic colorectal cancer samples with an atomic force microscope. STAR Protoc. 1, 100167 (2020).","journal-title":"STAR Protoc."},{"key":"2435_CR86","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.cmet.2019.03.013","volume":"30","author":"S Sato","year":"2019","unstructured":"Sato, S. et al. Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis. Cell Metab. 30, 92\u2013110 (2019).","journal-title":"Cell Metab."}],"updated-by":[{"DOI":"10.1038\/s41590-026-02485-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000}}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02435-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02435-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02435-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T08:02:45Z","timestamp":1773216165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02435-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":86,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["2435"],"URL":"https:\/\/doi.org\/10.1038\/s41590-026-02435-4","relation":{},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"19 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41590-026-02485-8","URL":"https:\/\/doi.org\/10.1038\/s41590-026-02485-8","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}