Muscle-specific overexpression of Atg2 gene and endurance exercise delay age-related deteriorations of skeletal muscle and heart function via activating the AMPK/Sirt1/PGC-1α pathway in male Drosophila
Muscle-specific overexpression of Atg2 gene and endurance exercise delay age-related deteriorations of skeletal muscle and heart function via activating the AMPK/Sirt1/PGC-1α pathway in male Drosophila
复制标题
肌肉特异性ATG2基因的过度表达和耐力运动通过激活AMPK/Sirt1/PGC-1α通路延缓雄性果蝇骨骼肌和心脏功能的增龄性恶化
DOI：
10.1096/fj.202301312r
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发表时间：
2023-11-01
期刊：
影响因子：
4.8
通讯作者：
Yin，Xin-Yuan
中科院分区：
文献类型：
--
作者：
Wang，Jing-Feng;Wen，Deng-Tai;Yin，Xin-Yuan
atg 2是自噬形成的关键基因，在调节衰老进程中起重要作用。运动是抵抗细胞氧化应激、延缓肌肉衰老的重要工具。然而，运动与肌肉Atg 2基因在调节骨骼肌衰老中的关系仍不清楚。在此，通过在果蝇中构建AtgUAS/MhcGal 4系统，实现肌肉Atg 2基因的过表达或敲低，并且这些果蝇也经受2周的运动干预。结果表明，Atg 2的过表达和运动都显着增加了衰老果蝇的攀爬速度，攀爬耐力，心脏功能和寿命。它们还显著上调了肌肉Atg 2、AMPK、Sirt 1和PGC-1α基因的表达，并显著降低了肌肉丙二醛和甘油三酯。当两者结合起来时，这些积极的好处更加明显。然而，Atg 2敲低对骨骼肌，心脏和寿命的影响与其过表达相比是逆转的。重要的是，运动改善了Atg 2敲低诱导的年龄相关变化。因此，目前的研究结果证实，肌肉Atg 2的过表达和运动都延迟了骨骼肌、心脏功能和寿命的年龄相关性恶化，运动也可以逆转Atg 2敲低诱导的年龄相关性变化。其分子机制与Atg 2基因的过表达和运动有关，这增加了AMPK/Sirt 1/PGC-1α通路的活性，氧化和抗氧化平衡以及衰老肌肉中的脂质代谢。
Atg2 is a key gene in autophagy formation and plays an important role in regulating aging progress. Exercise is an important tool to resist oxidative stress in cells and delay muscle aging. However, the relationship between exercise and the muscle Atg2 gene in regulating skeletal muscle aging remains unclear. Here, overexpression or knockdown of muscle Atg2 gene was achieved by constructing the AtgUAS/MhcGal4 system in Drosophila, and these flies were also subjected to an exercise intervention for 2 weeks. The results showed that both overexpression of Atg2 and exercise significantly increased the climbing speed, climbing endurance, cardiac function, and lifespan of aging flies. They also significantly up‐regulated the expression of muscle Atg2, AMPK, Sirt1, and PGC‐1α genes, and they significantly reduced muscle malondialdehyde and triglyceride. These positive benefits were even more pronounced when the two were combined. However, the effects of Atg2 knockdown on skeletal muscle, heart, and lifespan were reversed compared to its overexpression. Importantly, exercise ameliorated age‐related changes induced by Atg2 knockdown. Therefore, current results confirmed that both overexpression of muscle Atg2 and exercise delayed age‐related deteriorations of skeletal muscle, the heart function, and lifespan, and exercise could also reverse age‐related changes induced by Atg2 knockdown. The molecular mechanism is related to the overexpression of the Atg2 gene and exercise, which increase the activity of the AMPK/Sirt1/PGC‐1α pathway, oxidation and antioxidant balance, and lipid metabolism in aging muscle.