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首页> 美国卫生研究院文献>other >Short-term caloric restriction resveratrol or combined treatment regimens initiated in late-life alter mitochondrial protein expression profiles in a fiber-type specific manner in aged animals
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Short-term caloric restriction resveratrol or combined treatment regimens initiated in late-life alter mitochondrial protein expression profiles in a fiber-type specific manner in aged animals

机译：在衰老动物中以生命周期开始的短期热量限制白藜芦醇或联合治疗方案以纤维类型特异性方式改变线粒体蛋白表达谱

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Aging is associated with a loss in muscle known as sarcopenia that is partially attributed to apoptosis. In aging rodents, caloric restriction (CR) increases health and longevity by improving mitochondrial function and the polyphenol resveratrol (RSV) has been reported to have similar benefits. In the present study, we investigated the potential efficacy of using short-term (6 weeks) CR (20%), RSV (50 mg/kg/day), or combined CR + RSV (20% CR and 50 mg/kg/day RSV), initiated at late-life (27 months) to protect muscle against sarcopenia by altering mitochondrial function, biogenesis, content, and apoptotic signaling in both glycolytic white and oxidative red gastrocnemius muscle (WG and RG, respectively) of male Fischer 344 × Brown Norway rats. CR but not RSV attenuated the age-associated loss of muscle mass in both mixed gastrocnemius and soleus muscle, while combined treatment (CR + RSV) paradigms showed a protective effect in the soleus and plantaris muscle (P < 0.05). Sirt1 protein content was increased by 2.6-fold (P < 0.05) in WG but not RG muscle with RSV treatment, while CR or CR + RSV had no effect. PGC-1α levels were higher (2-fold) in the WG from CR-treated animals (P < 0.05) when compared to ad-libitum (AL) animals but no differences were observed in the RG with any treatment. Levels of the anti-apoptotic protein Bcl-2 were significantly higher (1.6-fold) in the WG muscle of RSV and CR + RSV groups compared to AL (P < 0.05) but tended to occur coincident with elevations in the pro-apoptotic protein Bax so that the apoptotic susceptibility as indicated by the Bax to Bcl-2 ratio was unchanged. There were no alterations in DNA fragmentation with any treatment in muscle from older animals. Additionally, mitochondrial respiration measured in permeabilized muscle fibers was unchanged in any treatment group and this paralleled the lack of change in cytochrome c oxidase (COX) activity. These data suggest that short-term moderate CR, RSV, or CR + RSV tended to modestly alter key mitochondrial regulatory and apoptotic signaling pathways in glycolytic muscle and this might contribute to the moderate protective effects against aging-induced muscle loss observed in this study.
机译：衰老与肌肉减少有关，称为肌肉减少症，部分归因于细胞凋亡。在老化的啮齿动物中，热量限制（CR）通过改善线粒体功能来提高健康和寿命，据报道多酚白藜芦醇（RSV）具有类似的益处。在本研究中，我们研究了短期（6周）CR（20％），RSV（50 mg / kg / day）或CR + RSV（20％CR和50 mg / kg /第一天（RSV），在生命的后期（27个月）启动，以通过改变男性Fischer 344的糖酵解性白色腓肠肌和氧化性红色腓肠肌（分别为WG和RG）的线粒体功能，生物发生，含量和凋亡信号来保护肌肉免受肌肉减少症×挪威褐鼠。 CR而非RSV减弱了腓肠肌和比目鱼混合肌中与年龄相关的肌肉质量损失，而联合治疗（CR + RSV）范式对比目鱼肌和plant肌具有保护作用（P <0.05）。 RSV处理后，WG中Sirt1蛋白含量增加了2.6倍（P <0.05），但RG肌肉没有增加，而CR或CR + RSV没有影响。与随意（AL）动物相比，CR处理动物的WG中PGC-1α水平更高（2倍）（P <0.05），但是在任何处理下RG中均未观察到差异。与AL相比，RSV和CR + RSV组的WG肌肉中抗凋亡蛋白Bcl-2的水平显着更高（1.6倍），但倾向于与促凋亡蛋白的升高同时发生Bax，从而使Bax与Bcl-2的比例所表明的凋亡敏感性保持不变。对老年动物的肌肉进行任何治疗后，DNA片段均无变化。此外，在任何治疗组中，通透性肌纤维中测量的线粒体呼吸均未改变，这与细胞色素C氧化酶（COX）活性缺乏变化平行。这些数据表明，短期中度CR，RSV或CR + RSV倾向于适度地改变糖酵解性肌肉中关键的线粒体调节和凋亡信号通路，这可能有助于针对本研究中观察到的针对衰老引起的肌肉损失的中度保护作用。

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