Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats

• DOI: 10.1007/s10522-014-9492-5
• Publication Date: 2014-03-20T13:47:27Z
• Authors: Sean M. Garvey; Janis E. Dugle; Adam D. Kennedy; Jonathan E. McDunn; William Kline; Lining Guo; Denis C. Guttridge; Suzette L. Pereira; Neile K. Edens
• Keywords: Gastrocnemius muscle; Muscle Atrophy; Carbohydrate Metabolism

Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several in particular undergo progressive atrophy degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling characterize trends metabolic changes between 15-month-old adult 32-month-old aged Fischer 344 × Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, markedly fewer signs of atrophy. Both were analyzed, as well plasma urine. Compared gastrocnemius, showed evidence reduced glycolytic metabolism, including accumulation glycolytic, glycogenolytic, pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels citrate nicotinamide adenine dinucleotide reduced, consistent mitochondrial abnormalities. Indicative 3-methylhistidine free amino acids gastrocnemius. monounsaturated fatty oleate, cis-vaccenate, palmitoleate also increased suggesting altered lipid metabolism. exhibited far carbohydrate but did show reductions several intermediates, fumarate, malate, flavin dinucleotide. Plasma biochemicals showing largest increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, creatine. These suggest insulin sensitivity Altogether, these data highlight group-specific perturbations glucose metabolism dysfunction