Alterations in glutamine synthetase activity in rat skeletal muscle are associated with advanced age

ObjectiveGlutamine synthetase (GS), a key enzyme in the production of glutamine, is preserved in skeletal muscle during early aging (<24 mo). Because the effects of advanced age on GS are unknown, we investigated the effect of advanced age (>24 mo) on GS activity in skeletal muscle. We hypothesized that advanced age would enhance muscle GS activity.MethodsMuscle GS activities were assessed in adult (8 mo), mature adult (15 mo), aged (20–22 mo), advanced age (25–27 mo), or very advanced age (29–32 mo) female Wistar rats. Male Wistar (6–27 mo) were used to investigate the effect of gender on this activity.ResultsGlutamine synthetase activity remained low and unaltered in rats from 8 to 22 mo of age, as previously demonstrated. In contrast, GS activity was high (∼75% of individual values were higher than the low value mean) in 25-mo to 27-mo-old rats. In very-old-aged rats (29–32 mo), ∼55% of GS activity data points exhibited low values. Changes in GS protein content paralleled those in GS activities. In male rats, GS activity was also high (∼80% of individual values were higher than the mean value of 6-mo to 19-mo-old rats) at the upper limit of life expectancy (27 mo).ConclusionThere is enhanced GS activity in old female and male rats suggesting a greater need for glutamine. In some very old rats, low GS activity may be associated with longevity or reflect a limitation in glutamine production due to extremely advanced age per se.