West Daniel W D, Marcotte George R, Chason Courtney M, Juo Natalie, Baehr Leslie M, Bodine Sue C, Baar Keith
Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA, United States.
Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, United States.
Front Physiol. 2019 Jan 14;9:1915. doi: 10.3389/fphys.2018.01915. eCollection 2018.
Anabolic resistance to feeding in aged muscle is well-characterized; however, whether old skeletal muscle is intrinsically resistant to acute mechanical loading is less clear. The aim of this study was to determine the impact of aging on muscle protein synthesis (MPS), ribosome biogenesis, and protein breakdown in skeletal muscle following a single bout of resistance exercise. Adult male F344/BN rats aged 10 (Adult) and 30 (Old) months underwent unilateral maximal eccentric contractions of the hindlimb. Precursor rRNA increased early post-exercise (6-18 h), preceding elevations in ribosomal mass at 48 h in Adult and Old; there were no age-related differences in these responses. MPS increased early post-exercise in both Adult and Old; however, at 48 h of recovery, MPS returned to baseline in Old but not Adult. This abbreviated protein synthesis response in Old was associated with decreased levels of IRS1 protein and increased BiP, CHOP and eIF2α levels. Other than these responses, anabolic signaling was similar in Adult and Old muscle in the acute recovery phase. Basal proteasome activity was lower in Old, and resistance exercise did not increase the activity of either the ATP-dependent or independent proteasome, or autophagy (Cathepsin L activity) in either Adult or Old muscle. We conclude that MPS and ribosome biogenesis in response to maximal resistance exercise in old skeletal muscle are initially intact; however, the MPS response is abbreviated in Old, which may be the result of ER stress and/or blunted exercise-induced potentiation of the MPS response to feeding.
衰老肌肉对进食的合成代谢抵抗已得到充分表征;然而,老年骨骼肌是否对急性机械负荷存在内在抵抗尚不清楚。本研究的目的是确定衰老对单次抗阻运动后骨骼肌中肌肉蛋白合成(MPS)、核糖体生物发生和蛋白分解的影响。10个月大(成年)和30个月大(老年)的成年雄性F344/BN大鼠进行后肢单侧最大离心收缩。前体rRNA在运动后早期(6 - 18小时)增加,早于成年和老年组在48小时时核糖体质量的升高;这些反应不存在年龄相关差异。成年和老年组运动后早期MPS均增加;然而,在恢复48小时时,老年组MPS恢复到基线水平,而成年组未恢复。老年组这种缩短的蛋白合成反应与IRS1蛋白水平降低以及BiP、CHOP和eIF2α水平升高有关。除了这些反应外,在急性恢复期,成年和老年肌肉中的合成代谢信号相似。老年组基础蛋白酶体活性较低,抗阻运动并未增加成年或老年肌肉中ATP依赖性或非依赖性蛋白酶体的活性,也未增加自噬(组织蛋白酶L活性)。我们得出结论,老年骨骼肌对最大抗阻运动的MPS和核糖体生物发生最初是完整的;然而,老年组的MPS反应缩短,这可能是内质网应激和/或运动诱导的MPS对进食反应的增强减弱的结果。