{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:55:36Z","timestamp":1793030136443,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T00:00:00Z","timestamp":1582588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30AR066262"],"award-info":[{"award-number":["P30AR066262"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG046282"],"award-info":[{"award-number":["R01AG046282"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age\u2010related diseases. Therefore, we investigated age\u2010related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24\u00a0months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3\u00a0months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA\u2010seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up\u2010regulation of M1\/pro\u2010inflammatory genes in macrophages from old mice as well as dysregulation of other immune\u2010related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age\u2010matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA\u2010seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age\u2010related changes, and depleting infiltrating macrophages can improve fracture healing in old mice.<\/jats:p>","DOI":"10.1111\/acel.13112","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T09:31:51Z","timestamp":1582623111000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Age\u2010related changes to macrophages are detrimental to fracture healing in mice"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-6498","authenticated-orcid":false,"given":"Daniel","family":"Clark","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery School of Medicine Orthopaedic Trauma Institute Zuckerberg San Francisco General Hospital University of California San Francisco San Francisco CA USA"},{"name":"Division of Periodontology Department of 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