Department of Physical Therapy and Assistive Technology, National Yang-Ming University, 155, Sec. 2, Li-nong St, Taipei, 112, Taiwan.
Department of Exercise and Health Science, College of Human Development and Health, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
Geroscience. 2019 Dec;41(6):871-880. doi: 10.1007/s11357-019-00109-8. Epub 2019 Nov 1.
In skeletal muscles, calorie restriction (CR) preserves muscle mass in middle-aged rats but not younger rats. The underlying mechanisms for this age-specific response are unknown. Skeletal muscle mass depends on several factors, with protein synthesis and degradation playing major roles. Therefore, the purpose of this study was to investigate whether CR affects younger and older animals differently on mTOR signaling and ubiquitin-proteasome pathway (UPP). Four-, 8-, and 16-month-old rats, with or without 40% CR for a duration of 14 weeks, were sacrificed after an overnight fasting. Total protein content and the phosphorylation level of AKT, mTOR, S6K, and 4EBP1 and protein content of key markers in the UPP (FOXO3a, atrogin, MuRF1, ubiquitinated proteins, proteasome subunits alpha 7 and beta 5) were determined. Unlike younger rats, CR decreased the content of phosphorylated mTOR, S6K, phosphorylated S6K, FOXO3a, and ubiquitinated proteins in middle-aged rats. In conclusion, CR-induced reduction of content/ phosphorylation levels of key proteins in mTOR signaling and the UPP occurred in the middle-aged rats but not younger rats. The age-dependent effects of CR on mTOR signaling and the UPP indirectly explained the age-related effects of CR on muscle mass of animals.
在骨骼肌中，热量限制（CR）可以维持中年大鼠的肌肉质量，但不能维持年轻大鼠的肌肉质量。这种年龄特异性反应的潜在机制尚不清楚。骨骼肌质量取决于多种因素，其中蛋白质合成和降解起着主要作用。因此，本研究旨在探讨 CR 是否对年轻和年老动物的 mTOR 信号和泛素-蛋白酶体途径（UPP）产生不同的影响。4 个月、8 个月和 16 个月大的大鼠，无论是否进行 40%的 CR，持续 14 周，经过一夜禁食后被处死。测定总蛋白含量和 AKT、mTOR、S6K 和 4EBP1 的磷酸化水平，以及 UPP 中的关键标志物（FOXO3a、atrogin、MuRF1、泛素化蛋白、蛋白酶体亚基 alpha 7 和 beta 5）的蛋白含量。与年轻大鼠不同，CR 降低了中年大鼠中磷酸化 mTOR、S6K、磷酸化 S6K、FOXO3a 和泛素化蛋白的含量。总之，CR 诱导的 mTOR 信号和 UPP 中关键蛋白的含量/磷酸化水平的降低仅发生在中年大鼠中，而不在年轻大鼠中。CR 对 mTOR 信号和 UPP 的年龄依赖性影响间接解释了 CR 对动物肌肉质量的年龄相关影响。
