Sarcopenia is not due to lack of regenerative drive in senescent skeletal muscle.
Sarcopenia, loss of skeletal muscle mass, is a hallmark of aging commonly attributed to a decreased capacity to maintain muscle tissue in senescence, yet the mechanism behind the muscle wasting remains unresolved. To address these issues we have explored a rodent model of sarcopenia and age-related sensorimotor impairment, allowing us to discriminate between successfully and unsuccessfully aged cohort members. Immunohistochemistry and staining of cell nuclei revealed that senescent muscle has an increased density of cell nuclei, occurrence of aberrant fibers and fibers expressing embryonic myosin. Using real-time PCR we extend the findings of increased myogenic regulatory factor mRNA to show that very high levels are found in unsuccessfully aged cohort members. This pattern is also reflected in the number of embryonic myosin-positive fibers, which increase with the degree of sarcopenia. In addition, we confirm that there is no local down-regulation of IGF-I and IGF-IR mRNA in aged muscle tissue; on the contrary, the most sarcopenic individuals showed significantly higher local expression of IGF-I mRNA. Combined, our results show that the initial drive to regenerate myofibers is most marked in cases with the most advanced loss of muscle mass, a pattern that may have its origin in differences in the rate of tissue deterioration and/or that regenerating myofibers in these cases fail to mature into functional fibers. Importantly, the genetic background is a determinant of the pace of progression of sarcopenia.
Edström
Erik
E
Experimntal Neurogerontology, Department of Neuroscience, Karolinska Institutet, S171 77 Stockholm, Sweden. erik.edstrome@neuro.ki.se
Ulfhake
Brun
B
D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006614:Hindlimb; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D018485:Muscle Fibers, Skeletal / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D012038:Regeneration
D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1