The effect of aging on skeletal muscle regeneration

Muscle atrophy and decreased strength are an accepted part of aging. While physical inactivity may account for some of these losses, physically active individuals still experience age related reduction in muscle mass and strength. The purpose of this study is to examine the effects that aging has on skeletal muscle regeneration. It is hypothesized that the recovery of muscle mass and force following muscular injury will decrease with age. The anesthetic bupivacaine, a potent myotoxic agent, was injected into the left tibialis anterior (TA) of young, adult, and senescent rats (3, 18, 31 months). The right leg served as an internal control. Following a 2, 3, or 4 week recovery period, the mass and isometric force of each TA were measured. In the young animals, the mass of the bupivacaine injected leg was 60% of the control value at two weeks post injection. By three weeks, the mass was fully recovered. In the middle age and senescent animals, mass of the injected TA was approximately 50% of the control at two weeks and remained at 50% of control following 3 and 4 weeks recovery. Muscle force measurements demonstrated parallel trends. These results indicate that skeletal muscle regeneration is impaired in middle age and senescent rats. Recently, a family of four genes was identified that causes the expression of skeletal muscle specific proteins when activated in precursor cells. One member of this family is myogenin. It is known that myogenin is expressed only during skeletal muscle regeneration, making it an excellent marker for this process. Myogenin mRNA levels were measured in the control and experimental TA muscles of the young, middle age, and senescent animals used in this experiment. All three age groups have elevated levels of myogenin mRNA in the bupivacaine-injected TA when compared to the control. In addition, the 31 month animals have significantly higher levels of myogenin mRNA in their control legs at all time periods than those found in the other age groups. It is known that the expression of myogenin is down-regulated by electrical activity. The high levels found in the control leg indicate reinnervation problems during regeneration in the old animals