Abstract
Studies suggest that carnosine (beta-alanyl-L-histidine) is effective in treating neuromuscular diseases associated with aging, but there is still a need to clarify its role in motor units (MUs) function during aging. In this study, 40 male Wistar rats aged 15 months were randomly assigned to a control or to two experimental groups in which 0.1% carnosine supplementation was performed for 10 or 34 weeks. After 34 weeks, we examined fast fatigable (FF), fast fatigue-resistant (FR) and slow (S) MUs’ force properties and fatigability, as well as antioxidant potential, advanced glycation end products, activity of enzymes, and histidyl dipeptides content in the medial gastrocnemius muscle. Short- and long-term carnosine supplementation maintained the force of FF MUs at a higher level during its rapid decline seen from the initial 10 to 70 s of the fatigue test. In FF, especially long-term, and in FR MUs, especially short-term, carnosine supplementation resulted in less rapid force decline during the initial 70 s of the second fatigue protocol. Carnosine supplementation did not change muscle antioxidant potential and mortality rate (~35% in all groups), nor muscle mass with aging. Moreover, instead of the expected increase, a decrease in histidyl dipeptides by ~30% in the red portion of medial gastrocnemius muscle after long-term supplementation was found. After chronic carnosine supplementation, the specific changes in fatigue resistance were observed in FF and FR units, but not in S MU types that were not accompanied by an improvement of antioxidant potential and activity of glycolytic or oxidative enzymes in aged rats. These observations indicate that carnosine supplementation during aging may generate different physiological adaptations which should be considered as an important factor when planning treatment strategies.
Highlights
Aging is associated with an excessive production of reactive oxygen and/or nitrogen species in skeletal muscle [1,2] which leads to overactivation of specific redox-sensitive signaling pathways involved in sarcopenia, and results in muscle weakness and decreased functionality [3,4]
Our findings suggest that the beneficial effects of carnosine on muscle contractility are not necessarily accompanied with the detectible increase in muscle histidyl dipeptides concentrations, but possibly may be mediated through other mechanisms of action of these dipeptides
Short- and long-term 0.1% oral carnosine supplementation in aged rats may be beneficial for partial counteraction of the rapid force decline of fast fatigable (FF) motor units (MUs), especially during functionally important, early stages (10–70 s) of fatiguing influences
Summary
Lower activity of oxidative enzyme citrate synthase has been noted in specific older lower limb muscles (i.e., gastrocnemius), despite previously reported shifts of the muscles towards a more oxidative profile with the aging process [9]. This suggests that, compared to the young, older individuals may have lower fatigue resistance to short- and long-lasting activity in isolated motor units, keeping a similar glycolytic or oxidative muscle fiber profile
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