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Metabolomic profiling of aging rat skeletal muscle
Author(s) -
Garvey Sean M.,
Guo Lining,
Kennedy Adam D.,
McDunn Jonathan E.,
Pereira Suzette L.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1202.15
Subject(s) - citric acid cycle , glycolysis , skeletal muscle , medicine , endocrinology , chemistry , metabolism , senescence , pentose phosphate pathway , nad+ kinase , soleus muscle , atrophy , biochemistry , metabolic pathway , biology , enzyme
Skeletal muscles undergo progressive atrophy and pathologic remodeling with age. To better understand muscle senescence, we used metabolomic profiling to characterize ‘adult’ (15‐month‐old; n=8) and ‘old’ (32‐month‐old; n=8) FBN male rats. Gastrocnemius (gastroc) and soleus muscles were analyzed, as well as plasma. Compared to adult gastroc, old gastroc showed evidence of altered glucose metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet tricarboxylic acid (TCA) cycle intermediates were reduced, and nicotinamide adenine dinucleotide was reduced 82% (p<0.0001). Indicative of muscle atrophy, 3‐methylhistidine and free amino acids were elevated in old gastroc. The monounsaturated fatty acids oleate, cis‐vaccenate, and palmitoleate, also increased in old gastroc. Old soleus showed reductions in glycolytic and TCA cycle intermediates, and 39% (p<0.0001) reduction in flavin adenine dinucleotide. Age‐related plasma biomarkers showing the largest % increases included glycocholate (218%), heme (122%), 1,5‐anhydroglucitol (119%), 1‐palmitoleoyl‐glycerophosphocholine (95%), palmitoleate (64%), and creatine (53%). These changes are consistent with reduced insulin sensitivity in aging. In sum, energetic dysfunction appears central to pathological metabolic processes in aging skeletal muscle.