Age-related alterations in the sarcolemmal environment are attenuated by lifelong caloric restriction and voluntary exercise.

Age-related alterations in the sarcolemmal environment are attenuated by lifelong caloric restriction and voluntary exercise.
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DOI:
10.1016/j.exger.2016.08.006
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发表时间:
2016-10
影响因子:
3.9
通讯作者:
Lawler, John M.
Lawler, John M.
中科院分区:
医学2区
文献类型:
--
作者:
Hord, Jeffrey M.;Botchlett, Rachel;Lawler, John M.

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骨骼肌质量和功能的减少,称为肌肉减少症,可以通过终身热量限制和运动来减轻。在老化的骨骼肌纤维中,细胞膜的完整性受损,这可能导致肌肉减少症。本研究的目的是确定终身轻度(8%)热量限制(CR)和终身CR +自愿轮跑(WR)是否可以改善衰老过程中膜支架和信号蛋白的破坏,从而维持足底肌纤维中有利的健康膜环境。将Fischer-344大鼠分为四组:24月龄成年大鼠自由进食(OAL); 24月龄大鼠限制8%热量摄入(OCR); 24月龄大鼠限制8%热量摄入+轮跑(OCRWR); 6月龄成年大鼠自由进食(YAL),以确定年龄相关的变化。衰老导致肌营养不良蛋白糖蛋白复合物(DGC)蛋白质:肌营养不良蛋白和α-突触营养蛋白的不连续膜表达。老年肌肉还显示神经元型一氧化氮合酶(nNOS),一个关键的DGC信号蛋白的含量减少。相比之下,OCR和OCRWR对年龄相关的DGC破坏提供了显着的保护。与年龄相关的膜DGC通畅性下降相结合,OAL植物中关键的膜修复蛋白(MG 53、dysferlin、膜联蛋白A6和膜联蛋白A2)显着增加。然而,终身CR和CRWR干预措施有效地维持膜修复蛋白接近YAL水平。OAL纤维也显示NADPH氧化酶亚型2(Nox 2)亚基(p67 phox和p47 phox)蛋白含量减少,与扰动的肌膜环境一致。Nox 2亚基的丢失被终身CR和CRWR阻止。因此,我们的研究结果是一致的假设,终身CR和WR是有效的对策,对年龄相关的改变,在肌纤维膜环境。
Age-related loss of skeletal muscle mass and function, referred to as sarcopenia, is mitigated by lifelong calorie restriction as well as exercise. In aged skeletal muscle fibers there is compromised integrity of the cell membrane that may contribute to sarcopenia. The purpose of this study was to determine if lifelong mild (8%) caloric restriction (CR) and lifelong CR + voluntary wheel running (WR) could ameliorate disruption of membrane scaffolding and signaling proteins during the aging process, thus maintaining a favorable, healthy membrane environment in plantaris muscle fibers. Fischer-344 rats were divided into four groups: 24-month old adults fed ad libitum (OAL); 24-month old on 8% caloric restriction (OCR); 24 month old 8% caloric restriction + wheel running (OCRWR); 6-month old sedentary adults fed ad libitum (YAL) were used to determine age-related changes. Aging resulted in discontinuous membrane expression of dystrophin glycoprotein complex (DGC) proteins: dystrophin and α-syntrophin. Older muscle also displayed decreased content of neuronal nitric oxide synthase (nNOS), a key DGC signaling protein. In contrast, OCR and OCRWR provided significant protection against age-related DGC disruption. In conjunction with the age-related decline in membrane DGC patency, key membrane repair proteins (MG53, dysferlin, annexin A6, and annexin A2) were significantly increased in the OAL plantaris. However, lifelong CR and CRWR interventions were effective at maintaining membrane repair proteins near YAL levels of. OAL fibers also displayed reduced protein content of NADPH oxidase isoform 2 (Nox2) subunits (p67phox and p47phox), consistent with a perturbed sarcolemmal environment. Loss of Nox2 subunits was prevented by lifelong CR and CRWR. Our results are therefore consistent with the hypothesis that lifelong CR and WR are effective countermeasures against age-related alterations in the myofiber membrane environment.
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