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We used in vivo pulsed SILAC labelling to quantify new protein incorporation into cartilage, bone, and skin of mice across the healthy life course. We report dynamic turnover of the matrisome, the proteins of the extracellular matrix, in bone and cartilage during skeletal maturation, which was markedly reduced after skeletal maturity. Comparing young adult with older adult mice, new protein incorporation was reduced in all tissues. STRING clustering revealed changes in epigenetic modulators across all tissues, a decline in chondroprotective growth factors such as FGF2 and TGF\u03b2 in cartilage, and clusters indicating mitochondrial dysregulation and reduced collagen synthesis in bone. Several pathways were implicated in age-related disease. Fewer changes were observed for skin. This methodology provides dynamic protein data at a tissue level, uncovering age-related molecular changes that may predispose to disease.<\/jats:p>","DOI":"10.7554\/elife.66635","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T09:46:03Z","timestamp":1632476763000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.66635","source":"Crossref","is-referenced-by-count":36,"title":["Age-dependent changes in protein incorporation into collagen-rich tissues of mice by in vivo pulsed SILAC labelling"],"prefix":"10.7554","volume":"10","author":[{"given":"Yoanna","family":"Ariosa-Morejon","sequence":"first","affiliation":[{"name":"Kennedy Institute of Rheumatology, Arthritis Research UK Centre for OA Pathogenesis, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Santos","sequence":"additional","affiliation":[{"name":"Big Data Institute, Li-Ka Shing Centre for Health 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