Derave Wim, Jones Glenys, Hespel Peter, Harris Roger C
Research Center for Exercise and Health, Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, KU Leuven, Leuven, Belgium.
Rejuvenation Res. 2008 Jun;11(3):641-7. doi: 10.1089/rej.2008.0699.
The histidine-containing dipeptides (HCD) carnosine and anserine are found in high concentrations in mammalian skeletal muscle. Given its versatile biologic properties, such as antioxidative, antiglycation, and pH buffering capacity, carnosine has been implicated as a protective factor in the aging process. The present study aimed to systematically explore age-related changes in skeletal muscles HCD content in a murine model of accelerated aging. Additionally, we investigated the effect of lifelong creatine supplementation on muscle HCD content and contractile fatiguability. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 weeks. At week 10, 25, and 60, tibialis anterior muscles were dissected and analysed for HCD and taurine content by HPLC. Soleus and EDL muscles were tested for in vitro contractile fatigue and recovery. From 10 to 60 weeks of age, muscular carnosine (-45%), taurine (-24%), and total creatine (-42%) concentrations gradually and significantly decreased. At 25 but not at 60 weeks, oral creatine supplementation significantly increased carnosine (+88%) and anserine (+40%) content compared to age-matched control-fed animals. Taurine and total creatine content were not affected by creatine supplementation at any age. Creatine-treated mice showed attenuated muscle fatigue (soleus) and enhanced force recovery (m. extensor digitorum longus [EDL]) compared to controls at 25 weeks, but not at 60 weeks. From the present study, we can conclude that skeletal muscle tissue exhibits a significant decline in HCD content at old age. Oral creatine supplementation is able to transiently but potently increase muscle carnosine and anserine content, which coincides with improved resistance to contractile fatigue.
含组氨酸的二肽（HCD）肌肽和鹅肌肽在哺乳动物骨骼肌中含量很高。鉴于其具有多种生物学特性，如抗氧化、抗糖基化和pH缓冲能力，肌肽被认为是衰老过程中的一种保护因子。本研究旨在系统地探讨加速衰老小鼠模型中骨骼肌HCD含量的年龄相关变化。此外，我们研究了终身补充肌酸对肌肉HCD含量和收缩疲劳性的影响。雄性衰老加速小鼠（SAMP8）从10周龄到60周龄分别喂食对照饮食或补充肌酸（食物摄入量的2%）的饮食。在第10、25和60周时，解剖胫骨前肌，通过高效液相色谱法分析HCD和牛磺酸含量。对比目鱼肌和趾长伸肌进行体外收缩疲劳和恢复测试。从10周龄到60周龄，肌肉中的肌肽（-45%）、牛磺酸（-24%）和总肌酸（-42%）浓度逐渐且显著下降。在25周时，与年龄匹配的对照喂养动物相比，口服补充肌酸显著增加了肌肽（+88%）和鹅肌肽（+40%）的含量，但在60周时没有。在任何年龄，补充肌酸都不会影响牛磺酸和总肌酸的含量。与对照组相比，在25周时，补充肌酸的小鼠肌肉疲劳减轻（比目鱼肌），力量恢复增强（趾长伸肌），但在60周时没有。从本研究中，我们可以得出结论，老年时骨骼肌组织中HCD含量显著下降。口服补充肌酸能够短暂但有效地增加肌肉中肌肽和鹅肌肽的含量，这与对收缩疲劳抵抗力的改善相吻合。
