{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:55:31Z","timestamp":1790574931058,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["2T32AG058527\u201006A1"],"award-info":[{"award-number":["2T32AG058527\u201006A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG021334"],"award-info":[{"award-number":["P30AG021334"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["5T32AR048522\u201020"],"award-info":[{"award-number":["5T32AR048522\u201020"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01\u2010AR075726"],"award-info":[{"award-number":["R01\u2010AR075726"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30AI094189"],"award-info":[{"award-number":["P30AI094189"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sarcopenia, the age\u2010related loss of muscle strength and mass, contributes to adverse health outcomes in older adults. Exercise engages calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    )\u2010 and redox\u2010dependent signaling pathways that enhance muscle performance and adaptation, whereas aging disrupts Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and redox homeostasis. CaMKII is a key transducer of both signals, raising the possibility that sustained CaMKII signaling becomes maladaptive with aging. Here, we show that CaMKII protein abundance is increased in aged mouse skeletal muscle and that sustained CaMKII activation in young muscle is sufficient to impair contractile function before substantial atrophy develops and, with prolonged activation, to promote progressive muscle loss. Sustained CaMKII activation also disrupted mitochondrial organization and shifted the young\u2010muscle transcriptome toward an aged profile characterized by inflammatory and stress\u2010response pathways. Inhibiting canonical NF\u2010\u03baB signaling partially preserved contractile force during prolonged CaMKII activation without preserving muscle mass, and mediation analysis implicated heme\/iron\u2010related transcriptional remodeling in the muscle\u2010mass\u2010independent decline in force. Conversely, expression of CN19o, a peptide inhibitor of CaMKII, in aged muscle improved contractile function and shifted the transcriptome away from an aging\u2010associated profile without inducing hypertrophy. Together, these findings identify sustained CaMKII signaling as a contributor to age\u2010associated muscle dysfunction and support a context\u2010dependent shift from adaptive CaMKII signaling in youth to maladaptive signaling in aging, consistent with antagonistic pleiotropy.\n                  <\/jats:p>","DOI":"10.1111\/acel.70704","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:40:01Z","timestamp":1789040401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sustained Activation of\n                    <scp>CaMKII<\/scp>\n                    Promotes Skeletal Muscle Contractile Dysfunction in Aging"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-4052","authenticated-orcid":false,"given":"Michael R.","family":"Bene","sequence":"first","affiliation":[{"name":"Division of Geriatric Medicine and Gerontology, Biology of Healthy Aging Program Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0270-5181","authenticated-orcid":false,"given":"Tae","family":"Chung","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab  Chicago Illinois USA"},{"name":"Department of Physical Medicine and Rehabilitation Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-089X","authenticated-orcid":false,"given":"Elizabeth D.","family":"Luczak","sequence":"additional","affiliation":[{"name":"Division of Cardiology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2600-067X","authenticated-orcid":false,"given":"Gabriel","family":"Lopez\u2010Cecetaite","sequence":"additional","affiliation":[{"name":"Division of Cardiology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7995-8160","authenticated-orcid":false,"given":"William A.","family":"Fountain","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine and Gerontology, Biology of Healthy Aging Program Johns Hopkins School of Medicine  Baltimore Maryland USA"},{"name":"School of Health and Human Sciences Indiana University Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-0671","authenticated-orcid":false,"given":"Giovanni","family":"Rosales\u2010Soto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1138-1382","authenticated-orcid":false,"given":"Erick","family":"Hern\u00e1ndez\u2010Ochoa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Antonescu","sequence":"additional","affiliation":[{"name":"Genetic Resources Core Facility, Computational Bioanalysis Division, and Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-2324","authenticated-orcid":false,"given":"Liliana","family":"Florea","sequence":"additional","affiliation":[{"name":"Genetic Resources Core Facility, Computational Bioanalysis Division, and Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9477-4057","authenticated-orcid":false,"given":"Seeun J.","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine and Gerontology, Biology of Healthy Aging Program Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9539-9520","authenticated-orcid":false,"given":"Emily","family":"Elassal","sequence":"additional","affiliation":[{"name":"College of Computer, Mathematical, and Natural Sciences University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2958-8149","authenticated-orcid":false,"given":"Anne","family":"Le","sequence":"additional","affiliation":[{"name":"Gigantest, Inc.  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