Resveratrol, a SIRT1 activator, attenuates aging-associated alterations in skeletal muscle and heart in mice.
Resveratrol, a SIRT1 activator, attenuates aging-associated alterations in skeletal muscle and heart in mice.
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白藜芦醇是一种 SIRT1 激活剂，可减轻小鼠骨骼肌和心脏与衰老相关的变化。
DOI：
10.1016/j.jphs.2023.04.001
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发表时间：
2023
影响因子：
3.5
通讯作者：
Kuno Atsushi
中科院分区：
文献类型：
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作者：
Hosoda Ryusuke;Nakashima Ryuta;Yano Masaki;Iwahara Naotoshi;Asakura Seidai;Nojima Iyori;Saga Yukika;Kunimoto Risa;Horio Yoshiyuki;Kuno Atsushi
衰老与多个器官的损伤有关，包括骨骼肌和心脏。在这项研究中，我们研究了白藜芦醇，一种NAD+依赖的蛋白脱乙酰基酶Sirtuin-1(SIRT1)的激活剂，是否可以减轻与年龄相关的小鼠骨骼肌减少和心肌细胞肥大。从28周龄开始用白藜芦醇(0.4 mg/kg饮食)治疗32周的小鼠，可以防止与衰老相关的旋转木马骑行时间缩短。直方图分析显示，60周龄(Wo)小鼠的胫前肌萎缩程度明显高于20周龄(Wo)小鼠，白藜芦醇可使萎缩的胫前肌缩小。在心脏方面，白藜芦醇减轻了与衰老相关的心肌细胞直径的增加。与20-wo小鼠相比，60-wo小鼠TA肌乙酰化蛋白增多，自噬活性降低。白藜芦醇治疗降低了TA肌肉中乙酰化蛋白的水平，并恢复了自噬活性。白藜芦醇也抑制了与衰老相关的心肌自噬的减少。骨骼肌特异性SIRT1基因敲除小鼠的TA肌肉中乙酰化蛋白和萎缩的肌肉纤维增加，自噬活性降低。这些结果表明，白藜芦醇处理激活SIRT1可通过恢复自噬来抑制小鼠的肌萎缩症和心肌肥大。
Aging is associated with impairment of multiple organs, including skeletal muscle and heart. In this study, we investigated whether resveratrol, an activator of an NAD+-dependent protein deacetylase Sirtuin-1 (SIRT1), attenuates age-related sarcopenia and cardiomyocyte hypertrophy in mice. Treatment of mice with resveratrol (0.4 g/kg diet) from 28 weeks of age for 32 weeks prevented aging-associated shortening of rotarod riding time. In the tibialis anterior (TA) muscle, histogram analysis showed that the atrophic muscle was increased in 60-week-old (wo) mice compared with 20-wo mice, which was attenuated by resveratrol. In the heart, resveratrol attenuated an aging-associated increase in the cardiomyocyte diameter. Acetylated proteins were increased and autophagic activity was reduced in the TA muscle of 60-wo mice compared with those of 20-wo mice. Resveratrol treatment reduced levels of acetylated proteins and restored autophagic activity in the TA muscle. Aging-related reduction in myocardial autophagy was also suppressed by resveratrol. Skeletal muscle-specific SIRT1 knockout mice showed increases in acetylated proteins and atrophic muscle fibers and reduced autophagic activity in the TA muscle. These results suggest that activation of SIRT1 by treatment with resveratrol suppresses sarcopenia and cardiomyocyte hypertrophy by restoration of autophagy in mice.