Increased aging in primary muscle cultures of sporadic inclusion-body myositis

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• 作者：Roberta Morosetti ; Aldobr ; o Broccolini ; Cristina Sancricca ; Carla Gliubizzi ; Teresa Gidaro ; Pietro A. Tonali ; Enzo Ricci ; Massimiliano Mirabella
• 关键词：Aging ; Cultured muscle ; Satellite cells ; s-IBM ; Muscle regeneration
• 刊名：Neurobiology of Aging
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：31
• 期：7
• 页码：1205-1214
• 全文大小：1049 K

文摘

Ageing is thought to participate to the pathogenesis of sporadic inclusion-body myositis (s-IBM). Although the regenerative potential of s-IBM muscle is reduced in vivo, age-related abnormalities of satellite cells possibly accounting for the decline of muscle repair have not been demonstrated. Here we show that proliferation rate and clonogenicity of s-IBM myoblasts are significantly lower and doubling time is longer than normal age-matched controls, indicating that proliferative capacity of s-IBM muscles becomes exhausted earlier. Telomere shortening is detected in s-IBM cells suggesting premature senescence. Differently from controls, s-IBM myoblasts show increased active β-catenin mainly localized within myonuclei, indicating active Wnt stimulation. After many rounds of muscle growth, only s-IBM myoblasts accumulate congophilic inclusions and immunoreactive Aβ_1–40 deposits. Therefore, s-IBM myoblasts seem to have a constitutively impaired regenerative capacity and the intrinsic property, upon sufficient aging in vitro, to accumulate Aβ. Our results might be valuable in understanding molecular mechanisms associated with muscle aging underlying the defective regeneration of s-IBM muscle and provide new clues for future therapeutic strategies.