AGE-RELATED ALTERATIONS OF SKELETAL-MUSCLE METABOLISM BY INTERMITTENTHYPOXIA AND TRH-ANALOG TREATMENT

The characteristics of the energy metabolism were evaluated in the gas trocnemius muscle from 3- and 24-month-old rats in normoxia or subject ed to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the followi ng metabolites related to the energy metabolism was evaluated: glycoge n, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvat e ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, g lutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate; energy charge potential. Furthermore the maximum rate of the following muscul ar enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate ki nase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; t otal NADH cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concent rations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activ ities. Ageing was characterized by a decrease in muscular creatine pho sphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobar ic mild and severe hypoxia-induced alterations of the components in th e anaerobic glycolytic pathway, tricarboxylic acid cycle and energy st orage, that were magnified in the skeletal muscle from the oldest anim als. The effect of the chronic treatment with the TRH-analogue posatir eline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular bioche mical mechanisms related to the energy transduction.