EFFECT OF AGING ON SKELETAL MUSCLE HYPERTROPHY, HYPERPLASIA AND REGENERATION1648

Abstract

To study effect of aging on muscle hypertrophy, hyperplasia and regeneration, we used a rat model of weight-lifting exercise described previously by our laboratory. This exercise successively inducing muscle hypertrophy, hyperplasia and regeneration. Wistar male rats aged 14-20 week-old were used for control group (CG), and over 120 week-old were used for old group (OG). Serial biochemical changes after the one bout of all-out exercise were examined. 3H-thymidine and 14C-leucine labeling were used to determine the changes in cellular mitotic activity (hyperplasia and regeneration) and the level of amino acid uptake and myosin synthesis(hypertrophy and hyperplasia), respectively, during 14 days after weight-lifting exercise. The intensity of the exercise and degree of muscle damage were monitored by serum creatine kinase (CK) activity. Tendency of muscle atrophy was evident in OG, and total lifting weight of OG was significantly lower than CG. Serum CK activity after the exercise was significantly increased in both group. The mitotic activity was not significantly changed in OG during 14 days, although peak increase at 2 days after exercise was apparently observed in CG. Furthermore, in the CG muscle,14 C-leucine uptake increased throughout the 14 days post-exercise period showing two cycle of increased uptake, during the first and second week. It is considered that increased amino-acid uptake during the first week, probably reflecting muscle hypertrophy and synthesis of other non-contractile related proteins. The uptake also increased during the second week probably due to muscle hyperplasia and regeneration. In the OG, however, only first week increase of leucine uptake was evident. These results suggest that ability of muscle hyperplasia and regeneration of old rat apparently decreased as represented by lower mitotic activity. However, ability of muscle hypertrophy that simply depend on protein synthesis derived by existing myonuclei was sufficiently remained in the OG muscle.