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Quiescent satellite cells are activated by physiological stimuli, injury or other traumatic insults for the repair of injuries or growth of the tissue. Activation of satellite cells induces proliferation and expression of MRFs, which in turn activate myogenic differentiation transcription programmes. Transitioning into and committing to terminal differentiation are regulated by myogenin and cell cycle exit markers, notably Rb1 and p21. Differentiation is then complete with the formation of new muscle fibres which incorporate into existing fibres. Upon ageing, the efficiency of differentiation is reduced as a consequence of a loss in the physiological balance between pathways regulating satellite cell quiescence and activation, notably the Notch and Wnt pathways, and increased senescence of the satellite cell pool. Extracellular factors involved in the dysregulation of differentiation upon ageing include low\u2010grade chronic inflammation and remodelling of the extracellular matrix by fibro\u2010adipogenic progenitor cells, thereby negatively affecting the differentiation capacity of satellite cells, resulting in either premature differentiation or senescence. These ageing\u2010associated alterations in muscle homeostasis appear to be amplified in inclusion body myositis (IBM), an idiopathic inflammatory myopathy that almost exclusively manifests in individuals over 45\u2009years of age, making it a prototypical age\u2010related muscle disease. IBM is characterised by chronic inflammation, progressive muscle degeneration and premature ageing of both muscle tissue and the satellite cell niche. Studied with immunohistochemical techniques and multi\u2010omics, muscle biopsy tissue demonstrated increased expression of MRFs as well as increased expression of senescence and genomic stress markers. IBM primary myoblasts demonstrated premature ageing and senescence and increased activity of the Wnt pathway, though differentiation into multinucleated myotubes did not show notable aberrations in signalling pathways or differentiation efficiency. In conclusion, ageing and chronic inflammation lead to dysregulation of key pathways that, in turn, alter the capacity of satellite cells to activate and proliferate, leading to prematurely aged satellite cells that still retain their capacity to differentiate into myofibres. Though in IBM there is an increased abundance of active differentiation markers, reflecting a regenerative response to the massive, sustained muscle atrophy, senescence of the satellite cell niche may impair effective regeneration of the lost muscle tissue.<\/jats:p>","DOI":"10.1002\/jcsm.70301","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:02:30Z","timestamp":1777867350000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ageing\u2010Associated Dysregulation of Myogenic Differentiation in Inclusion Body Myositis"],"prefix":"10.1002","volume":"17","author":[{"given":"Geert\u00a0M.","family":"de Vries","sequence":"first","affiliation":[{"name":"Translational Neurosciences and Peripheral Neuropathy Group University of Antwerp  Antwerp Belgium"},{"name":"Laboratory of Neuromuscular Pathology, Institute Born\u2010Bunge University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"De\u00a0Ridder","sequence":"additional","affiliation":[{"name":"Translational Neurosciences and Peripheral Neuropathy Group University of Antwerp  Antwerp Belgium"},{"name":"Laboratory of Neuromuscular Pathology, Institute Born\u2010Bunge University of Antwerp  Antwerp Belgium"},{"name":"Department of Neurology, Neuromuscular Reference Centre Antwerp University Hospital  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Baets","sequence":"additional","affiliation":[{"name":"Translational Neurosciences and Peripheral Neuropathy Group University of Antwerp  Antwerp Belgium"},{"name":"Laboratory of Neuromuscular Pathology, Institute Born\u2010Bunge University of Antwerp  Antwerp Belgium"},{"name":"Department of Neurology, Neuromuscular Reference Centre Antwerp University Hospital  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2021.02.006"},{"key":"e_1_2_11_3_1","first-page":"2559","volume-title":"Adult Stem Cells at Work: Regenerating Skeletal Muscle. 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