{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:58:50Z","timestamp":1788886730495,"version":"build-2803163510"},"reference-count":272,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"#NEXTGENERATIONEU (NGEU)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"#NEXTGENERATIONEU (NGEU)","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}]},{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sporadic inclusion body myositis (sIBM) is the most common muscle disease of older people and is clinically characterized by slowly progressive asymmetrical muscle weakness, predominantly affecting the quadriceps, deep finger flexors, and foot extensors. At present, there are no enduring treatments for this relentless disease that eventually leads to severe disability and wheelchair dependency. Although sIBM is considered a rare muscle disorder, its prevalence is certainly higher as the disease is often undiagnosed or misdiagnosed. The histopathological phenotype of sIBM muscle biopsy includes muscle fiber degeneration and endomysial lymphocytic infiltrates that mainly consist of cytotoxic CD8+ T cells surrounding nonnecrotic muscle fibers expressing MHCI. Muscle fiber degeneration is characterized by vacuolization and the accumulation of congophilic misfolded multi-protein aggregates, mainly in their non-vacuolated cytoplasm. Many players have been identified in sIBM pathogenesis, including environmental factors, autoimmunity, abnormalities of protein transcription and processing, the accumulation of several toxic proteins, the impairment of autophagy and the ubiquitin\u2013proteasome system, oxidative and nitrative stress, endoplasmic reticulum stress, myonuclear degeneration, and mitochondrial dysfunction. Aging has also been proposed as a contributor to the disease. However, the interplay between these processes and the primary event that leads to the coexistence of autoimmune and degenerative changes is still under debate. Here, we outline our current understanding of disease pathogenesis, focusing on degenerative mechanisms, and discuss the possible involvement of aging.<\/jats:p>","DOI":"10.3390\/ijms25052742","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T11:52:55Z","timestamp":1709034775000},"page":"2742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0968-0498","authenticated-orcid":false,"given":"Valeria","family":"Guglielmi","sequence":"first","affiliation":[{"name":"Cellular and Molecular Biology of Cancer Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"},{"name":"Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1829-6917","authenticated-orcid":false,"given":"Marta","family":"Cheli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Tonin","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3412-8339","authenticated-orcid":false,"given":"Gaetano","family":"Vattemi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1212\/01.wnl.0000192260.33106.bb","article-title":"Inclusion-body myositis: Clinical, diagnostic, and pathologic aspects","volume":"66","author":"Engel","year":"2006","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1212\/WNL.28.1.8","article-title":"Inclusion body myositis: A distinct variety of idiopathic inflammatory myopathy","volume":"28","author":"Carpenter","year":"1978","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3233\/JND-150138","article-title":"Mortality and Causes of Death in Patients with Sporadic Inclusion Body Myositis: Survey Study Based on the Clinical Experience of Specialists in Australia, Europe and the USA","volume":"3","author":"Price","year":"2016","journal-title":"J. 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