title: Contributions of the ubiquitin-proteasome pathway and apoptosis to human skeletal muscle wasting with age.
abstract: The primary mechanism that contributes to decreasing skeletal muscle strength and size with healthy aging is not presently known. This study examined the contribution of the ubiquitin-proteasome pathway and apoptosis to skeletal muscle wasting in older adults (n = 21; mean age = 72.76 +/- 8.31 years) and young controls (n = 21; mean age = 21.48 +/- 2.93 years). Subjects underwent a percutaneous muscle biopsy of the vastus lateralis to determine: (1) ubiquitin ligase gene expression (MAFbx and MuRF1); (2) frequency of apoptosis; and (3) individual fiber type and cross-sectional area. In addition, a whole muscle strength test was also performed. A one-way ANOVA revealed significant increases in the number of positive TUNEL cells in older adults (87%; p < 0.05), although no significant increase in caspase-3/7 activity was detected. Additionally, ubiquitin ligase gene expression, individual muscle fiber type and CSA were not different between old and young subjects. Muscle strength was also significantly lower in old compared to young subjects (p < 0.05). In conclusion, this study indicates a preferential role for apoptosis contributing to decreases in muscle function with age.
authors.affiliation: Applied Physiology Laboratory, University of Kansas, 1301 Sunnyside Ave, Robinson Center Room 101DJ, Lawrence, KS 66045, USA.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Whitman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wacker
authors.forename: Scott R
authors.initials: SR
authors.lastname: Richmond
authors.forename: Michael P
authors.initials: MP
authors.lastname: Godard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D009124:Muscle Proteins / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D009133:Muscular Atrophy / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D044843:SKP Cullin F-Box Protein Ligases / Q000502:physiology; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex