Modified Calcium Homeostasis in Aged Mouse Skeletal Muscle

In aging decreased physical activity and reduced muscle mass (sarcopenia) leads to impaired muscle force and increased fatigability accompanied by a decline in sarcoplasmic reticulum (SR) calcium release. As an essential trace element selenium plays a significant role in muscle functions, as in selenium deficiency skeletal muscle disorders manifesting in muscle pain, fatigue, proximal weakness, and serum creatine kinase elevation could develop. Here in vivo physical activity of control and myostatin deficient (Cmpt) mice during 22 months were examined. Their performance in grip and voluntary wheel tests reached its maximum 3 month after birth and declined after 10 month. This decrease was faster in Cmpt mice as the average daily running distance decreased to 37% in control and to 25% in Cmpt mice in old age. In vitro force was measured on soleus and extensor digitorum longus (EDL) muscles from 20-month-old control, Cmpt, and selenium supplemented mice. Albeit the absolute force was higher in Cmpt than in control mice, after normalization to cross section EDL was significantly stronger in the latter (4.70±0.88 vs 7.61±0.96 mN/mm2, respectively). Selenium supplementation significantly increased the maximal force of EDL (10.89±0.60 mN/mm2). Changes in intracellular calcium concentration were measured on enzymatically isolated intact flexor digitorum brevis muscle fibers using Fura-2. The rate of KCl depolarization-evoked SR calcium release was greater in selenium supplemented than in control animals (691±100 vs 481±33 µM/s, respectively). Western-blot analysis revealed no change in the expression of the dihydropyridine receptor in the three animal groups while that of the ryanodine receptor declined with aging which was reversed by long-term training. Our results support the positive effects of selenium and training on SR calcium release in old age associated muscle weakness. On the other hand, the increased muscle mass of Cmpt mice during their lifespan doesn’t improve their physical performance in old age. Supported by: NKFIH-K-115461