{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:46:50Z","timestamp":1791960410835,"version":"4.3.4"},"reference-count":92,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23H03308"],"award-info":[{"award-number":["23H03308"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG092299"],"award-info":[{"award-number":["R01AG092299"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG090356"],"award-info":[{"award-number":["R01AG090356"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG052978"],"award-info":[{"award-number":["R01AG052978"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG061005"],"award-info":[{"award-number":["R01AG061005"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG087565"],"award-info":[{"award-number":["R01AG087565"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Aging"],"DOI":"10.1038\/s43587-026-01225-9","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:03:33Z","timestamp":1790672613000},"page":"2164-2184","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise enhances aged chondrocyte health through microRNA-29-enriched extracellular vesicles"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-1502","authenticated-orcid":false,"given":"Hirotaka","family":"Iijima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandarp M.","family":"Dave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8447-6177","authenticated-orcid":false,"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3011-8010","authenticated-orcid":false,"given":"Adam M.","family":"Khay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8991-6546","authenticated-orcid":false,"given":"Ella","family":"D\u2019Amico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Yee","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee J.","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6800-9368","authenticated-orcid":false,"given":"John M.","family":"Jakicic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5497-5968","authenticated-orcid":false,"given":"Fabrisia","family":"Ambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"1225_CR1","doi-asserted-by":"publisher","first-page":"E320","DOI":"10.1152\/ajpendo.00215.2020","volume":"319","author":"J Denham","year":"2020","unstructured":"Denham, J. & Spencer, S. J. Emerging roles of extracellular vesicles in the intercellular communication for exercise-induced adaptations. Am. J. Physiol. Endocrinol. Metab. 319, E320\u2013E329 (2020).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"1225_CR2","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1093\/biosci\/biv084","volume":"65","author":"MP Zaborowski","year":"2015","unstructured":"Zaborowski, M. P., Balaj, L., Breakefield, X. O. & Lai, C. P. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience 65, 783\u2013797 (2015).","journal-title":"Bioscience"},{"key":"1225_CR3","doi-asserted-by":"publisher","first-page":"605","DOI":"10.3389\/fphys.2020.00605","volume":"11","author":"VD Nair","year":"2020","unstructured":"Nair, V. D. et al. Sedentary and trained older men have distinct circulating exosomal microRNA profiles at baseline and in response to acute exercise. Front. Physiol. 11, 605 (2020).","journal-title":"Front. Physiol."},{"key":"1225_CR4","doi-asserted-by":"publisher","first-page":"100055","DOI":"10.1016\/j.crmeth.2021.100055","volume":"1","author":"PM Vanderboom","year":"2021","unstructured":"Vanderboom, P. M. et al. A size-exclusion-based approach for purifying extracellular vesicles from human plasma. Cell Rep. Methods 1, 100055 (2021).","journal-title":"Cell Rep. Methods"},{"key":"1225_CR5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s00395-017-0628-z","volume":"112","author":"Y Bei","year":"2017","unstructured":"Bei, Y. et al. Exercise-induced circulating extracellular vesicles protect against cardiac ischemia-reperfusion injury. Basic Res. Cardiol. 112, 38 (2017).","journal-title":"Basic Res. Cardiol."},{"key":"1225_CR6","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nrendo.2016.76","volume":"12","author":"A Safdar","year":"2016","unstructured":"Safdar, A., Saleem, A. & Tarnopolsky, M. A. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat. Rev. Endocrinol. 12, 504\u2013517 (2016).","journal-title":"Nat. Rev. Endocrinol."},{"key":"1225_CR7","doi-asserted-by":"publisher","first-page":"6328","DOI":"10.1073\/pnas.0914843107","volume":"107","author":"DM Pegtel","year":"2010","unstructured":"Pegtel, D. M. et al. Functional delivery of viral miRNAs via exosomes. Proc. Natl Acad. Sci. USA 107, 6328\u20136333 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1225_CR8","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1101\/gad.1937010","volume":"24","author":"H Herranz","year":"2010","unstructured":"Herranz, H. & Cohen, S. M. MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems. Genes Dev. 24, 1339\u20131344 (2010).","journal-title":"Genes Dev."},{"key":"1225_CR9","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/nrendo.2015.25","volume":"11","author":"P Arner","year":"2015","unstructured":"Arner, P. & Kulyt\u00e9, A. MicroRNA regulatory networks in human adipose tissue and obesity. Nat. Rev. Endocrinol. 11, 276\u2013288 (2015).","journal-title":"Nat. Rev. Endocrinol."},{"key":"1225_CR10","doi-asserted-by":"publisher","first-page":"W65","DOI":"10.1093\/nar\/gky408","volume":"46","author":"AK Wong","year":"2018","unstructured":"Wong, A. K., Krishnan, A. & Troyanskaya, O. G. GIANT 2.0: genome-scale integrated analysis of gene networks in tissues. Nucleic Acids Res. 46, W65\u2013W70 (2018).","journal-title":"Nucleic Acids Res."},{"key":"1225_CR11","doi-asserted-by":"publisher","first-page":"20870","DOI":"10.1073\/pnas.0810772105","volume":"105","author":"K Lage","year":"2008","unstructured":"Lage, K. et al. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes. Proc. Natl Acad. Sci. USA 105, 20870\u201320875 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1225_CR12","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nrrheum.2016.65","volume":"12","author":"RF Loeser","year":"2016","unstructured":"Loeser, R. F., Collins, J. A. & Diekman, B. O. Ageing and the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 12, 412\u2013420 (2016).","journal-title":"Nat. Rev. Rheumatol."},{"key":"1225_CR13","unstructured":"GBD 2021 Osteoarthritis Collaborators. Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 5, e508\u2013e522 (2023)."},{"key":"1225_CR14","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.joca.2014.01.003","volume":"22","author":"TE McAlindon","year":"2014","unstructured":"McAlindon, T. E. et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr. Cartil. 22, 363\u2013388 (2014).","journal-title":"Osteoarthr. Cartil."},{"key":"1225_CR15","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/j.joca.2016.12.008","volume":"6","author":"H Iijima","year":"2017","unstructured":"Iijima, H. et al. Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model. Osteoarthr. Cartil. 6, 964\u2013975 (2017).","journal-title":"Osteoarthr. Cartil."},{"key":"1225_CR16","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.stem.2018.02.003","volume":"22","author":"TA Rando","year":"2018","unstructured":"Rando, T. A. & Ambrosio, F. Regenerative rehabilitation: applied biophysics meets stem cell therapeutics. Cell Stem Cell 22, 306\u2013309 (2018).","journal-title":"Cell Stem Cell"},{"key":"1225_CR17","doi-asserted-by":"publisher","first-page":"W521","DOI":"10.1093\/nar\/gkaa309","volume":"48","author":"F Kern","year":"2020","unstructured":"Kern, F. et al. miEAA 2.0: integrating multi-species microRNA enrichment analysis and workflow management systems. Nucleic Acids Res. 48, W521\u2013W528 (2020).","journal-title":"Nucleic Acids Res."},{"key":"1225_CR18","first-page":"D148","volume":"48","author":"H-Y Huang","year":"2020","unstructured":"Huang, H.-Y. et al. miRTarBase 2020: updates to the experimentally validated microRNA\u2013target interaction database. Nucleic Acids Res. 48, D148\u2013D154 (2020).","journal-title":"Nucleic Acids Res."},{"key":"1225_CR19","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/jcp.21237","volume":"213","author":"AL Berrier","year":"2007","unstructured":"Berrier, A. L. & Yamada, K. M. Cell\u2013matrix adhesion. J. Cell Physiol. 213, 565\u2013573 (2007).","journal-title":"J. Cell Physiol."},{"key":"1225_CR20","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1152\/physiolgenomics.00141.2011","volume":"44","author":"AJ Kriegel","year":"2012","unstructured":"Kriegel, A. J., Liu, Y., Fang, Y., Ding, X. & Liang, M. The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury. Physiol. Genomics 44, 237\u2013244 (2012).","journal-title":"Physiol. Genomics"},{"key":"1225_CR21","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/s41592-025-02994-8","volume":"23","author":"RSG Sealfon","year":"2026","unstructured":"Sealfon, R. S. G. et al. HumanBase: an interactive AI platform for human biology. Nat. Methods 23, 483\u2013484 (2026).","journal-title":"Nat. Methods"},{"key":"1225_CR22","doi-asserted-by":"publisher","first-page":"5408","DOI":"10.1111\/jcmm.15204","volume":"24","author":"Z Zhao","year":"2020","unstructured":"Zhao, Z. et al. Mechanotransduction pathways in the regulation of cartilage chondrocyte homoeostasis. J. Cell. Mol. Med. 24, 5408\u20135419 (2020).","journal-title":"J. Cell. Mol. Med."},{"key":"1225_CR23","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1113\/expphysiol.1984.sp002805","volume":"69","author":"A Knight","year":"1984","unstructured":"Knight, A. & Levick, J. R. Morphometry of the ultrastructure of the blood\u2013joint barrier in the rabbit knee. Q. J. Exp. Physiol. 69, 271\u2013288 (1984).","journal-title":"Q. J. Exp. Physiol."},{"key":"1225_CR24","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/bioinformatics\/bty637","volume":"35","author":"A Valdeolivas","year":"2019","unstructured":"Valdeolivas, A. et al. Random walk with restart on multiplex and heterogeneous biological networks. Bioinformatics 35, 497\u2013505 (2019).","journal-title":"Bioinformatics"},{"key":"1225_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35359-2","volume":"14","author":"H Iijima","year":"2023","unstructured":"Iijima, H. et al. Age-related matrix stiffening epigenetically regulates \u03b1-Klotho expression and compromises chondrocyte integrity. Nat. Commun. 14, 18 (2023).","journal-title":"Nat. Commun."},{"key":"1225_CR26","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1146\/annurev-bioeng-071114-040829","volume":"17","author":"JM Phillip","year":"2015","unstructured":"Phillip, J. M., Aifuwa, I., Walston, J. & Wirtz, D. The mechanobiology of aging. Annu. Rev. Biomed. Eng. 17, 113\u2013141 (2015).","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"1225_CR27","doi-asserted-by":"publisher","first-page":"6829","DOI":"10.18632\/aging.204248","volume":"14","author":"T Schmauck-Medina","year":"2022","unstructured":"Schmauck-Medina, T. et al. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging 14, 6829\u20136839 (2022).","journal-title":"Aging"},{"key":"1225_CR28","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nnano.2008.410","volume":"4","author":"M Stolz","year":"2009","unstructured":"Stolz, M. et al. Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat. Nanotechnol. 4, 186\u2013192 (2009).","journal-title":"Nat. Nanotechnol."},{"key":"1225_CR29","doi-asserted-by":"publisher","first-page":"101393","DOI":"10.1016\/j.arr.2021.101393","volume":"70","author":"M Selman","year":"2021","unstructured":"Selman, M. & Pardo, A. Fibroageing: an ageing pathological feature driven by dysregulated extracellular matrix-cell mechanobiology. Ageing Res. Rev. 70, 101393 (2021).","journal-title":"Ageing Res. Rev."},{"key":"1225_CR30","doi-asserted-by":"publisher","first-page":"9424","DOI":"10.1073\/pnas.1505700112","volume":"112","author":"JH Kim","year":"2015","unstructured":"Kim, J. H. et al. Matrix cross-linking-mediated mechanotransduction promotes posttraumatic osteoarthritis. Proc. Natl Acad. Sci. USA 112, 9424\u20139429 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1225_CR31","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1007\/s10735-013-9502-y","volume":"44","author":"W Zhong","year":"2013","unstructured":"Zhong, W. et al. YAP-mediated regulation of the chondrogenic phenotype in response to matrix elasticity. J. Mol. Histol. 44, 587\u2013595 (2013).","journal-title":"J. Mol. Histol."},{"key":"1225_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/srep20395","volume":"6","author":"J Du","year":"2016","unstructured":"Du, J. et al. Extracellular matrix stiffness dictates Wnt expression through integrin pathway. Sci. Rep. 6, 20395 (2016).","journal-title":"Sci. Rep."},{"key":"1225_CR33","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41368-022-00165-5","volume":"14","author":"C Zhou","year":"2022","unstructured":"Zhou, C. et al. Microenvironmental stiffness mediates cytoskeleton re-organization in chondrocytes through laminin-FAK mechanotransduction. Int J. Oral Sci. 14, 15 (2022).","journal-title":"Int J. Oral Sci."},{"key":"1225_CR34","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.pcad.2013.09.012","volume":"56","author":"DL Swift","year":"2014","unstructured":"Swift, D. L., Johannsen, N. M., Lavie, C. J., Earnest, C. P. & Church, T. S. The role of exercise and physical activity in weight loss and maintenance. Prog. Cardiovasc. Dis. 56, 441\u2013447 (2014).","journal-title":"Prog. Cardiovasc. Dis."},{"key":"1225_CR35","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1038\/s43587-021-00143-2","volume":"1","author":"A Sahu","year":"2021","unstructured":"Sahu, A. et al. Regulation of aged skeletal muscle regeneration by circulating extracellular vesicles. Nat. Aging 1, 1148\u20131161 (2021).","journal-title":"Nat. Aging"},{"key":"1225_CR36","doi-asserted-by":"publisher","first-page":"e12404","DOI":"10.1002\/jev2.12404","volume":"13","author":"JA Welsh","year":"2024","unstructured":"Welsh, J. A. et al. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J. Extracell. Vesicles 13, e12404 (2024).","journal-title":"J. Extracell. Vesicles"},{"key":"1225_CR37","doi-asserted-by":"publisher","first-page":"3336","DOI":"10.1002\/jcp.30094","volume":"236","author":"B Est\u00e9banez","year":"2021","unstructured":"Est\u00e9banez, B., Jim\u00e9nez-Pav\u00f3n, D., Huang, C. J., Cuevas, M. J. & Gonz\u00e1lez-Gallego, J. Effects of exercise on exosome release and cargo in in vivo and ex vivo models: a systematic review. J. Cell Physiol. 236, 3336\u20133353 (2021).","journal-title":"J. Cell Physiol."},{"key":"1225_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-10-r100","volume":"7","author":"AE Carpenter","year":"2006","unstructured":"Carpenter, A. E. et al. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 7, R100 (2006).","journal-title":"Genome Biol."},{"key":"1225_CR39","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.matbio.2014.08.007","volume":"39","author":"RF Loeser","year":"2014","unstructured":"Loeser, R. F. Integrins and chondrocyte-matrix interactions in articular cartilage. Matrix Biol. 39, 11\u201316 (2014).","journal-title":"Matrix Biol."},{"key":"1225_CR40","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","volume":"110","author":"RO Hynes","year":"2002","unstructured":"Hynes, R. O. Integrins: bidirectional, allosteric signaling machines. Cell 110, 673\u2013687 (2002).","journal-title":"Cell"},{"key":"1225_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81378-2","volume":"11","author":"T Kanamoto","year":"2021","unstructured":"Kanamoto, T. et al. Integrin \u03b12\u03b21 plays an important role in the interaction between human articular cartilage-derived chondrocytes and atelocollagen gel. Sci. Rep. 11, 1757 (2021).","journal-title":"Sci. Rep."},{"key":"1225_CR42","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","volume":"44","author":"M Kanehisa","year":"2016","unstructured":"Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44, D457\u2013D462 (2016).","journal-title":"Nucleic Acids Res."},{"key":"1225_CR43","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/npp.2012.112","volume":"38","author":"LD Moore","year":"2013","unstructured":"Moore, L. D., Le, T. & Fan, G. DNA methylation and its basic function. Neuropsychopharmacology 38, 23\u201338 (2013).","journal-title":"Neuropsychopharmacology"},{"key":"1225_CR44","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1093\/gerona\/glab386","volume":"77","author":"H Iijima","year":"2022","unstructured":"Iijima, H. et al. Meta-analysis integrated with multi-omics data analysis to elucidate pathogenic mechanisms of age-related knee osteoarthritis in mice. J. Gerontol. A Biol. Sci. Med. Sci. 77, 1321\u20131334 (2022).","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"1225_CR45","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41684-022-00986-1","volume":"51","author":"SJ Jackson","year":"2017","unstructured":"Jackson, S. J. et al. Does age matter? The impact of rodent age on study outcomes. Lab. Anim. 51, 160\u2013169 (2017).","journal-title":"Lab. Anim."},{"key":"1225_CR46","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1097\/PHM.0000000000002161","volume":"102","author":"K Chowdhary","year":"2023","unstructured":"Chowdhary, K. et al. Aging affects the efficacy of platelet-rich plasma treatment for osteoarthritis. Am. J. Phys. Med. Rehabil. 102, 597\u2013604 (2023).","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"1225_CR47","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1161\/HYPERTENSIONAHA.109.144428","volume":"55","author":"Y Liu","year":"2010","unstructured":"Liu, Y. et al. Renal medullary microRNAs in Dahl salt-sensitive rats: miR-29b regulates several collagens and related genes. Hypertension 55, 974\u2013982 (2010).","journal-title":"Hypertension"},{"key":"1225_CR48","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1016\/j.ajpath.2013.08.027","volume":"183","author":"V Ramdas","year":"2013","unstructured":"Ramdas, V., McBride, M., Denby, L. & Baker, A. H. Canonical transforming growth factor-\u03b2 signaling regulates disintegrin metalloprotease expression in experimental renal fibrosis via miR-29. Am. J. Pathol. 183, 1885\u20131896 (2013).","journal-title":"Am. J. Pathol."},{"key":"1225_CR49","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/MAJ.0b013e318267680d","volume":"346","author":"J Cheng","year":"2013","unstructured":"Cheng, J., Wang, Y., Wang, D. & Wu, Y. Identification of collagen 1 as a post-transcriptional target of miR-29b in skin fibroblasts: therapeutic implication for scar reduction. Am. J. Med. Sci. 346, 98\u2013103 (2013).","journal-title":"Am. J. Med. Sci."},{"key":"1225_CR50","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.15252\/emmm.201303604","volume":"6","author":"RL Montgomery","year":"2014","unstructured":"Montgomery, R. L. et al. MicroRNA mimicry blocks pulmonary fibrosis. EMBO Mol. Med. 6, 1347\u20131356 (2014).","journal-title":"EMBO Mol. Med."},{"key":"1225_CR51","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.1038\/s41598-017-03616-w","volume":"7","author":"J-Y Ko","year":"2017","unstructured":"Ko, J.-Y. et al. MicroRNA-29a counteracts synovitis in knee osteoarthritis pathogenesis by targeting VEGF. Sci. Rep. 7, 3584 (2017).","journal-title":"Sci. Rep."},{"key":"1225_CR52","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.bbi.2012.04.006","volume":"26","author":"N Kawanishi","year":"2012","unstructured":"Kawanishi, N. et al. Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet-induced obesity in mice. Brain Behav. Immun. 26, 931\u2013941 (2012).","journal-title":"Brain Behav. Immun."},{"key":"1225_CR53","doi-asserted-by":"publisher","first-page":"103","DOI":"10.14348\/molcells.2016.2179","volume":"39","author":"X Li","year":"2016","unstructured":"Li, X., Zhen, Z., Tang, G., Zheng, C. & Yang, G. MiR-29a and MiR-140 protect chondrocytes against the anti-proliferation and cell matrix signaling changes by IL-1\u03b2. Mol. Cells 39, 103\u2013110 (2016).","journal-title":"Mol. Cells"},{"key":"1225_CR54","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.ymthe.2019.01.008","volume":"27","author":"H Wang","year":"2019","unstructured":"Wang, H. et al. Exosome-mediated miR-29 transfer reduces muscle atrophy and kidney fibrosis in mice. Mol. Ther. 27, 571\u2013583 (2019).","journal-title":"Mol. Ther."},{"key":"1225_CR55","doi-asserted-by":"publisher","first-page":"4977","DOI":"10.2147\/IJN.S442876","volume":"19","author":"EY Lin","year":"2024","unstructured":"Lin, E. Y. et al. Engineered exosomes containing microRNA-29b-2 and targeting the somatostatin receptor reduce presenilin 1 expression and decrease the \u03b2-amyloid accumulation in the brains of mice with Alzheimer\u2019s disease. Int. J. Nanomed. 19, 4977\u20134994 (2024).","journal-title":"Int. J. Nanomed."},{"key":"1225_CR56","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01508-4","volume":"20","author":"R Chen","year":"2022","unstructured":"Chen, R. et al. Delivery of engineered extracellular vesicles with miR-29b editing system for muscle atrophy therapy. J. Nanobiotechnology 20, 304 (2022).","journal-title":"J. Nanobiotechnology"},{"key":"1225_CR57","doi-asserted-by":"publisher","first-page":"eaao0475","DOI":"10.1126\/scitranslmed.aao0475","volume":"10","author":"MC Lampi","year":"2018","unstructured":"Lampi, M. C. & Reinhart-King, C. A. Targeting extracellular matrix stiffness to attenuate disease: from molecular mechanisms to clinical trials. Sci. Transl. Med. 10, eaao0475 (2018).","journal-title":"Sci. Transl. Med."},{"key":"1225_CR58","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1021\/acs.nanolett.0c04834","volume":"21","author":"S Guo","year":"2021","unstructured":"Guo, S. et al. Stimulating extracellular vesicles production from engineered tissues by mechanical forces. Nano Lett. 21, 2497\u20132504 (2021).","journal-title":"Nano Lett."},{"key":"1225_CR59","doi-asserted-by":"publisher","first-page":"8210","DOI":"10.1002\/jcp.29476","volume":"235","author":"T Najrana","year":"2020","unstructured":"Najrana, T. et al. Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells. J. Cell Physiol. 235, 8210\u20138223 (2020).","journal-title":"J. Cell Physiol."},{"key":"1225_CR60","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1249\/MSS.0000000000003549","volume":"57","author":"M Yamagata","year":"2025","unstructured":"Yamagata, M., Kimura, T., Chang, A. H. & Iijima, H. Sex differences in ambulatory biomechanics: a meta-analysis providing a mechanistic insight into knee osteoarthritis. Med. Sci. Sports Exerc. 57, 144\u2013153 (2025).","journal-title":"Med. Sci. Sports Exerc."},{"key":"1225_CR61","doi-asserted-by":"crossref","unstructured":"Vechetti, I. J. Jr, Valentino, T., Mobley, C. B. & McCarthy, J. J. The role of extracellular vesicles in skeletal muscle and systematic adaptation to exercise. J. Physiol. 599, 845\u2013861 (2021).","DOI":"10.1113\/JP278929"},{"key":"1225_CR62","doi-asserted-by":"publisher","first-page":"a029827","DOI":"10.1101\/cshperspect.a029827","volume":"8","author":"A Safdar","year":"2018","unstructured":"Safdar, A. & Tarnopolsky, M. A. Exosomes as mediators of the systemic adaptations to endurance exercise. Cold Spring Harb. Perspect. Med. 8, a029827 (2018).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"1225_CR63","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.jshs.2023.11.001","volume":"13","author":"M Kotewitsch","year":"2024","unstructured":"Kotewitsch, M., Heimer, M., Schmitz, B. & Mooren, F. C. Non-coding RNAs in exercise immunology: a systematic review. J. Sport Health Sci. 13, 311\u2013338 (2024).","journal-title":"J. Sport Health Sci."},{"key":"1225_CR64","doi-asserted-by":"publisher","first-page":"100992","DOI":"10.1016\/j.jshs.2024.100992","volume":"14","author":"L Sun","year":"2025","unstructured":"Sun, L. et al. GEPREP: A comprehensive data atlas of RNA-seq-based gene expression profiles of exercise responses. J. Sport Health Sci. 14, 100992 (2025).","journal-title":"J. Sport Health Sci."},{"key":"1225_CR65","doi-asserted-by":"crossref","unstructured":"Law, C. W. et al. RNA-seq analysis is easy as 1-2-3 with limma, Glimma and edgeR. F1000Res 5, ISCB Comm J-1408 (2016).","DOI":"10.12688\/f1000research.9005.2"},{"key":"1225_CR66","first-page":"1438","volume":"5","author":"Y Chen","year":"2016","unstructured":"Chen, Y., Lun, A. T. & Smyth, G. K. From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline. F1000Res 5, 1438 (2016).","journal-title":"F1000Res"},{"key":"1225_CR67","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"1225_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29","volume":"15","author":"CW Law","year":"2014","unstructured":"Law, C. W., Chen, Y., Shi, W. & Smyth, G. K. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).","journal-title":"Genome Biol."},{"key":"1225_CR69","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"1225_CR70","doi-asserted-by":"publisher","first-page":"e14043","DOI":"10.1111\/acel.14043","volume":"23","author":"H Iijima","year":"2024","unstructured":"Iijima, H., Zhang, F., Ambrosio, F. & Matsui, Y. Network-based cytokine inference implicates Oncostatin M as a driver of an inflammation phenotype in knee osteoarthritis. Aging Cell 23, e14043 (2024).","journal-title":"Aging Cell"},{"key":"1225_CR71","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.ajhg.2008.02.013","volume":"82","author":"S K\u00f6hler","year":"2008","unstructured":"K\u00f6hler, S., Bauer, S., Horn, D. & Robinson, P. N. Walking the interactome for prioritization of candidate disease genes. Am. J. Hum. Genet. 82, 949\u2013958 (2008).","journal-title":"Am. J. Hum. Genet."},{"key":"1225_CR72","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1113\/JP285349","volume":"603","author":"H Iijima","year":"2025","unstructured":"Iijima, H., Ambrosio, F. & Matsui, Y. Network-based systematic dissection of exercise-induced inhibition of myosteatosis in older individuals. J. Physiol. 603, 45\u201367 (2025).","journal-title":"J. Physiol."},{"key":"1225_CR73","doi-asserted-by":"publisher","first-page":"e70683","DOI":"10.1111\/acel.70683","volume":"25","author":"TJ McNeill","year":"2026","unstructured":"McNeill, T. J., Ambrosio, F. & Iijima, H. Network model to predict age-related transcriptional reprogramming. Aging Cell 25, e70683 (2026).","journal-title":"Aging Cell"},{"key":"1225_CR74","doi-asserted-by":"publisher","first-page":"S92","DOI":"10.1002\/pmrj.70150","volume":"18","author":"NB Katz","year":"2026","unstructured":"Katz, N. B. et al. Relaxin-2 as a modifiable hormonal pathway in knee osteoarthritis: dose dependent effects on chondrocyte phenotype. PM R 18, S92\u2013S103 (2026).","journal-title":"PM R"},{"key":"1225_CR75","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics 16, 284\u2013287 (2012).","journal-title":"Omics"},{"key":"1225_CR76","doi-asserted-by":"publisher","first-page":"3429","DOI":"10.1021\/pr200021n","volume":"10","author":"HM Moore","year":"2011","unstructured":"Moore, H. M. et al. Biospecimen reporting for improved study quality (BRISQ). J. Proteome Res. 10, 3429\u20133438 (2011).","journal-title":"J. Proteome Res."},{"key":"1225_CR77","doi-asserted-by":"publisher","first-page":"e12385","DOI":"10.1002\/jev2.12385","volume":"12","author":"F Lucien","year":"2023","unstructured":"Lucien, F. et al. MIBlood-EV: minimal information to enhance the quality and reproducibility of blood extracellular vesicle research. J. Extracell. Vesicles 12, e12385 (2023).","journal-title":"J. Extracell. Vesicles"},{"key":"1225_CR78","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","volume":"7","author":"C Th\u00e9ry","year":"2018","unstructured":"Th\u00e9ry, C. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 7, 1535750 (2018).","journal-title":"J. Extracell. Vesicles"},{"key":"1225_CR79","doi-asserted-by":"publisher","first-page":"5443","DOI":"10.1021\/acs.nanolett.9b01943","volume":"19","author":"K Wang","year":"2019","unstructured":"Wang, K. et al. Substrate stiffness-dependent carbon nanotube-induced lung fibrogenesis. Nano Lett. 19, 5443\u20135451 (2019).","journal-title":"Nano Lett."},{"key":"1225_CR80","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07253-3","volume":"9","author":"A Sahu","year":"2018","unstructured":"Sahu, A. et al. Age-related declines in \u03b1-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration. Nat. Commun. 9, 4859 (2018).","journal-title":"Nat. Commun."},{"key":"1225_CR81","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","volume":"224","author":"S Bolte","year":"2006","unstructured":"Bolte, S. & Cordeli\u00e8res, F. P. A guided tour into subcellular colocalization analysis in light microscopy. J. Microsc. 224, 213\u2013232 (2006).","journal-title":"J. Microsc."},{"key":"1225_CR82","doi-asserted-by":"publisher","first-page":"C723","DOI":"10.1152\/ajpcell.00462.2010","volume":"300","author":"KW Dunn","year":"2011","unstructured":"Dunn, K. W., Kamocka, M. M. & McDonald, J. H. A practical guide to evaluating colocalization in biological microscopy. Am. J. Physiol. Cell Physiol. 300, C723\u2013C742 (2011).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"1225_CR83","doi-asserted-by":"crossref","unstructured":"Flurkey, K., Currer, J. M. & Harrison, D. Mouse models in aging research. in The Mouse in Biomedical Research 637\u2013672 (Elsevier, 2007).","DOI":"10.1016\/B978-012369454-6\/50074-1"},{"key":"1225_CR84","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","volume":"18","author":"SS Glasson","year":"2010","unstructured":"Glasson, S. S., Chambers, M. G., Van Den Berg, W. B. & Little, C. B. The OARSI histopathology initiative\u2014recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthr. Cartil. 18, S17\u2013S23 (2010).","journal-title":"Osteoarthr. Cartil."},{"key":"1225_CR85","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.joca.2013.10.007","volume":"22","author":"D Hayashi","year":"2014","unstructured":"Hayashi, D. et al. Pre-radiographic osteoarthritic changes are highly prevalent in the medial patella and medial posterior femur in older persons: Framingham OA study. Osteoarthr. Cartil. 22, 76\u201383 (2014).","journal-title":"Osteoarthr. Cartil."},{"key":"1225_CR86","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.joca.2021.01.006","volume":"29","author":"AR Armstrong","year":"2021","unstructured":"Armstrong, A. R., Carlson, C. S., Rendahl, A. K. & Loeser, R. F. Optimization of histologic grading schemes in spontaneous and surgically-induced murine models of osteoarthritis. Osteoarthr. Cartil. 29, 536\u2013546 (2021).","journal-title":"Osteoarthr. Cartil."},{"key":"1225_CR87","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","volume":"14","author":"KP Pritzker","year":"2006","unstructured":"Pritzker, K. P. et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthr. Cartil. 14, 13\u201329 (2006).","journal-title":"Osteoarthr. Cartil."},{"key":"1225_CR88","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-017-0428-1","volume":"9","author":"E Ntoumou","year":"2017","unstructured":"Ntoumou, E. et al. Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes. Clin. Epigenetics 9, 127 (2017).","journal-title":"Clin. Epigenetics"},{"key":"1225_CR89","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/ki.2011.445","volume":"81","author":"Y-C Sun","year":"2012","unstructured":"Sun, Y.-C., Chang, S.-C. & Wu, M.-S. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 81, 640\u2013650 (2012).","journal-title":"Kidney Int."},{"key":"1225_CR90","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 18, e3000410 (2020).","journal-title":"PLoS Biol."},{"key":"1225_CR91","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/164_2019_284","volume":"257","author":"CH Emmerich","year":"2020","unstructured":"Emmerich, C. H. & Harris, C. M. Minimum information and quality standards for conducting, reporting, and organizing in vitro research. Handb. Exp. Pharmacol. 257, 177\u2013196 (2020).","journal-title":"Handb. Exp. Pharmacol."},{"key":"1225_CR92","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/S0197-2456(98)00037-3","volume":"19","author":"WD Dupont","year":"1998","unstructured":"Dupont, W. D. & Plummer, W. D. Jr. Power and sample size calculations for studies involving linear regression. Control Clin. Trials 19, 589\u2013601 (1998).","journal-title":"Control Clin. Trials"}],"container-title":["Nature Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01225-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01225-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01225-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:07:14Z","timestamp":1791958034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01225-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":92,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["1225"],"URL":"https:\/\/doi.org\/10.1038\/s43587-026-01225-9","relation":{},"ISSN":["2662-8465"],"issn-type":[{"value":"2662-8465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"20 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}