title: Myostatin is associated with age-related human muscle stem cell dysfunction.
abstract: Human aging is accompanied by a progressive loss of muscle mass (sarcopenia). We tested the hypothesis that older males (OMs, 70±4 yr, n=9) would have a blunted myogenic response to a physiological stimulus compared to younger controls (21±3 yr, n=9). Subjects completed an acute bout of intense unilateral muscle loading. Young healthy males matched for body mass and activity level served as the control group. Muscle biopsies and blood were obtained before and at 3, 24, and 48 h after muscle loading. The muscle stem cell response was analyzed using flow cytometry, immunofluorescent microscopy, and standard protein and mRNA analysis. OMs had 35% fewer basal stem cells and a type II fiber-specific impairment in stem cell content and proliferation. Myogenic determination factor staining and cell cycle analysis illustrated a severely blunted progression through the myogenic program. Myostatin protein and mRNA were 2-fold higher in OMs. Stem cell-specific myostatin levels were not different at baseline; however, there were 67% more myostatin-positive type II-associated stem cells in OMs at 24 h. These data illustrate an age-related impairment of stem cell function in a fiber type-specific manner. The greater colocalization of myostatin with stem cells provides a mechanism for the impaired myogenic capacity of aged muscle.
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, ON, Canada, L8S 4L8.
authors.forename: Bryon R
authors.initials: BR
authors.lastname: McKay
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Ogborn
authors.forename: Leeann M
authors.initials: LM
authors.lastname: Bellamy
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
authors.forename: Gianni
authors.initials: G
authors.lastname: Parise
mesh_terms: D030301:Activin Receptors, Type II / Q000032:analysis; D000368:Aged; D000375:Aging / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D015444:Exercise / Q000502:physiology; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D017570:MyoD Protein / Q000032:analysis; D055435:Myostatin / Q000502:physiology*; D051763:PAX7 Transcription Factor; D012333:RNA, Messenger / Q000378:metabolism; D055948:Sarcopenia / Q000503:physiopathology*; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D055815:Young Adult
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D055435:Myostatin; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D012333:RNA, Messenger; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B