Guglielmi, V.; Cheli, M.; Tonin, P.; Vattemi, G. Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging. Int. J. Mol. Sci.2024, 25, 2742.
Guglielmi, V.; Cheli, M.; Tonin, P.; Vattemi, G. Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging. Int. J. Mol. Sci. 2024, 25, 2742.
Guglielmi, V.; Cheli, M.; Tonin, P.; Vattemi, G. Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging. Int. J. Mol. Sci.2024, 25, 2742.
Guglielmi, V.; Cheli, M.; Tonin, P.; Vattemi, G. Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging. Int. J. Mol. Sci. 2024, 25, 2742.
Abstract
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 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 histopathogical 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 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, accumulation of several toxic proteins, impairment of autophagy and ubiquitin proteasome system, oxidative and nitrative stress, endoplasmic reticulum stress, myonuclear degeneration, and mitochondrial dysfunction. Aging has been also 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.
Keywords
sporadic inclusion body myositis (sIBM); muscle fiber degeneration; protein aggregation; inflammation; aging; inflammaging.
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
