title: Severe atrophy of slow myofibers in aging muscle is concealed by myosin heavy chain co-expression.
abstract: Although slow myofibers are considered less susceptible to atrophy with aging, slow fiber atrophy may have been underestimated previously. First, the marked atrophy of the aging rat soleus (Sol) muscle cannot be explained by the atrophy of only the fast fibers, due to their low abundance. Second, the increase in small fibers co-expressing both fast and slow myosin heavy chains (MHC) in the aging rat Sol is proportional to a decline in pure MHC slow fibers (Snow et al., 2005), suggesting that these MHC co-expressing fibers represent formerly pure slow fibers. Thus, we examined the size and proportion of MHC slow, MHC fast, and MHC fast-slow co-expressing fibers in the Sol and mixed region of the gastrocnemius (Gas) muscle in young adult (YA) and senescent (SEN) rats. Our results suggest that formerly pure MHC slow fibers are the source of MHC co-expressing fibers with aging in both muscle regions. Accounting for the atrophy of these fibers in calculating MHC slow fiber atrophy with aging revealed that MHC slow fibers atrophy on average by 40% in the Sol and by 38% in the mixed Gas, values which are similar to the 60% and 31% atrophy of pure MHC fast fibers in the Sol and mixed Gas, respectively. Probing for the atrophy-dependent ubiquitin ligase, MAFbx (atrogin 1), it was suggested that former slow fibers acquire atrophy potential via the up-regulation of MAFbx coincident with the co-expression of fast MHC. These results redefine the impact of aging on slow fiber atrophy, and emphasize the necessity of addressing the atrophy of fast and slow fibers in seeking treatments for aging muscle atrophy.
authors.affiliation: Muscle Aging Diagnostics Laboratory, Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Fennigje M
authors.initials: FM
authors.lastname: Purves-Smith
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Solbak
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Rowan
authors.forename: Russell T
authors.initials: RT
authors.lastname: Hepple
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D008297:Male; D018613:Microscopy, Confocal; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; D018995:Myosin Heavy Chains