Methionine is an essential sulphur-containing amino acid involved in protein synthesis, regulation of protein function and methylation reactions. Dietary methionine restriction (0.12–0.17% methionine in food) extends the life span of various animal species and delays the onset of aging-associated diseases and cancers. In the liver, methionine restriction attenuates steatosis and delays the development of non-alcoholic steatohepatitis due to antioxidative action and metabolic reprogramming. The limited intake of methionine stimulates the fatty acid oxidation in the liver and the export of lipoproteins as well as inhibits de novo lipogenesis. These effects are mediated by various signaling pathways and effector molecules, including sirtuins, growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding proteins, adenosine monophosphate-dependent kinase and general control nonderepressible 2 pathway. Additionally, methionine restriction stimulates the synthesis of fibroblast growth factor-21 in the liver, which increases the insulin sensitivity of peripheral tissues. In the brain, methionine restriction delays the onset of neurodegenerative diseases and increases the resistance to various forms of stress through antioxidative effects and alterations in lipid composition. This review aimed to summarize the morphological, functional and molecular changes in the liver and brain caused by the methionine restriction, with possible implications in the prolongation of maximal life span.

中文翻译：

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饮食蛋氨酸限制对肝脏和大脑功能和代谢重编程的影响——对长寿的影响

蛋氨酸是一种必需的含硫氨基酸，参与蛋白质合成、蛋白质功能调节和甲基化反应。饮食中的蛋氨酸限制（食物中 0.12-0.17% 的蛋氨酸）可延长各种动物物种的寿命，并延缓与衰老相关的疾病和癌症的发生。在肝脏中，由于抗氧化作用和代谢重编程，限制蛋氨酸可减轻脂肪变性并延缓非酒精性脂肪性肝炎的发展。蛋氨酸的有限摄入会刺激肝脏中的脂肪酸氧化和脂蛋白的输出，并抑制从头脂肪生成。这些作用由各种信号通路和效应分子介导，包括sirtuins、生长激素/胰岛素样生长因子-1 轴、甾醇调节元件结合蛋白、一磷酸腺苷依赖性激酶和一般控制非抑制性2 通路。此外，限制蛋氨酸可刺激肝脏中成纤维细胞生长因子 21 的合成，从而增加外周组织的胰岛素敏感性。在大脑中，限制蛋氨酸可延缓神经退行性疾病的发作，并通过抗氧化作用和脂质成分的改变增加对各种形式压力的抵抗力。本综述旨在总结蛋氨酸限制引起的肝脏和大脑的形态、功能和分子变化，