Age-related changes in the mitotic and metabolic characteristics of muscle-derived cells.

Age-related sarcopenia could partly result from cumulative repeated episodes of incomplete repair and regeneration. We hypothesized that mitotic and metabolic events associated with satellite cell activation and proliferation could be altered with aging. Muscle-derived cells (mdc) were isolated from gastrocnemius and quadriceps muscles of young (3 wk old), adult (9 mo old), and old (24 mo old) Sprague-Dawley male rats (n = 10/group). The mdc from young growing rats started to proliferate earlier compared with adult and old animals. Cell cycle duration was significantly reduced with aging from 36.5 +/- 3.2 to 28.0 +/- 2.2 h. However, the proportion of noncycling (G0 phase) and cycling (G1 + S + G2 + M phases) cultured mdc was statistically unchanged among the three age groups. Significantly lower increase in c-met and proliferating cell nuclear antigen expression were observed in cultured mdc of old rats upon serum stimulation. Major changes in the expression of citrate synthase, lactate dehydrogenase, proteasome, caspase 3, plasminogen activators (PAs), and matrix metalloproteinase 2-9 (MMP2-9) were observed upon serum stimulation, but no age-related difference was noted. However, when measured on crushed muscle extracts, PAs and MMP2-9 enzyme activities were significantly decreased with aging. Our results show that cellular and biochemical events associated with the control of mdc activation and proliferation occur with aging. These alterations may participate in the accumulation of repeated episodes of incomplete repair and regeneration throughout the life span, thus contributing to the loss of skeletal muscle mass and function with aging.

Mitotic activity of rat muscle satellite cells in response to serum stimulation: relation with cellular metabolism.

Cellular and molecular adaptations of satellite cells isolated from rat hindlimb muscles (n = 10) were investigated in response to serum stimulation. Flow cytometry analysis of the amounts of DNA and RNA indicated that 97.7 +/- 0.7% of satellite cells were in G0 at the end of the isolation procedure, whereas 93.2 +/- 2.0% of cells were cycling after serum exposure. The length of cell division was 34.0 +/- 2.8 h. Myoblast proliferation was asynchronous, suggesting the existence of heterogeneous cell populations in skeletal muscle. Myoblast proliferation was also accompanied by a significant increase in c-met expression, and major adaptations of energetic and proteolytic metabolisms, including an increase in the relative contribution of glycolytic metabolism for energy production, an increase in proteasome and matrix metalloproteinases 2 and 9 activities, and a decrease in plasminogen activator activities. Our data suggest that, along with molecular adaptations leading to cell cycle activation itself, adaptations in energetic and proteolytic metabolisms are crucial events involved in satellite cell activation and myoblast proliferation.