Mass spectrometry-based proteomic analysis of middle-aged vs. aged vastus lateralis reveals increased levels of carbonic anhydrase isoform 3 in senescent human skeletal muscle.
The age-related loss of skeletal muscle mass and associated progressive decline in contractile strength is a serious pathophysiological issue in the elderly. In order to investigate global changes in the skeletal muscle proteome after the fifth decade of life, this study analysed total extracts from human vastus lateralis muscle by fluorescence difference in-gel electrophoresis. Tissue specimens were derived from middle-aged (47-62 years) vs. aged (76-82 years) individuals and potential changes in the protein expression profiles were compared between these two age groups by a comprehensive gel electrophoresis-based survey. Age-dependent alterations in the concentration of 19 protein spots were revealed and mass spectrometry identified these components as being involved in the excitation-contraction-relaxation cycle, muscle metabolism, ion handling and the cellular stress response. This indicates a generally perturbed protein expression pattern in senescent human muscle. Increased levels of mitochondrial enzymes and isoform switching of the key contractile protein, actin, support the idea of glycolytic-to-oxidative and fast-to-slow transition processes during muscle aging. Importantly, the carbonic anhydrase (CA)3 isoform displayed an increased abundance during muscle aging, which was independently verified by immunoblotting of differently aged human skeletal muscle samples. Since the CA3 isoform is relatively muscle-specific and exhibits a fibre type-specific expression pattern, this enzyme may represent an interesting new biomarker of sarcopenia. Increased levels of CA are indicative of an increased demand of CO₂-removal in senescent muscle, and also suggest age-related fibre type shifting to slower-contracting muscles during human aging.
Department of Biology, National University of Ireland, Maynooth,                     Kildare, Ireland.
Lisa
L
Staunton
Margit
M
Zweyer
Dieter
D
Swandulla
Kay
K
Ohlendieck
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000595:Amino Acid Sequence; D024403:Carbonic Anhydrase III / Q000032:analysis*; D006801:Humans; D015151:Immunoblotting; D013058:Mass Spectrometry; D008875:Middle Aged; D008969:Molecular Sequence Data; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D052097:Quadriceps Muscle / Q000201:enzymology*
D020543:Proteome; D024403:Carbonic Anhydrase III