Excitation-Contraction Uncoupling and Sarcopenia

The molecular and cellular mechanisms underlying sarcopenia, the age-related decline in muscle mass and strength, are not fully understood. It has been proposed that a reduced level of calcium ion-supply to contractile muscle proteins via excitation-contraction uncoupling leads to the muscle weakness associated with aging. The basic process of excitation-contraction uncoupling is a result of a larger number of ryanodine receptors being uncoupled to the voltage-sensing dihydropyridine receptor units. Other mechanisms of sarcopenia include reduced protein synthesis, mitochondrial dysfunction, inadequate nutrition, reduction in hormone levels and neuromuscular changes. In animal models of sarcopenia, a drastic decline in the α1S-subunit of the dihydropyridine receptor was observed. However, immunoblot analysis of vastus lateralis specimens from male humans aged 18 to 82 years of age showed no major changes in the relative abundance of this transverse-tubular receptor. In addition, the oligomeric status of the α1S-dihydropyridine receptor was unaltered in aged human fibres. It would appear therefore that dihydropyridine receptor expression is preserved during the aging process of human skeletal muscle fibres. Thus, the assumption that abnormal triadic signal transduction is responsible for sarcopenia can not be transferred from animal models to senescent human muscle without modifications.