Kitada Munehiro, Ogura Yoshio, Monno Itaru, Xu Jing, Koya Daisuke
Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
Biomedicines. 2021 Jan 29;9(2):130. doi: 10.3390/biomedicines9020130.
Enhanced oxidative stress is closely related to aging and impaired metabolic health and is influenced by diet-derived nutrients and energy. Recent studies have shown that methionine restriction (MetR) is related to longevity and metabolic health in organisms from yeast to rodents. The effect of MetR on lifespan extension and metabolic health is mediated partially through a reduction in oxidative stress. Methionine metabolism is involved in the supply of methyl donors such as S-adenosyl-methionine (SAM), glutathione synthesis and polyamine metabolism. SAM, a methionine metabolite, activates mechanistic target of rapamycin complex 1 and suppresses autophagy; therefore, MetR can induce autophagy. In the process of glutathione synthesis in methionine metabolism, hydrogen sulfide (HS) is produced through cystathionine-β-synthase and cystathionine-γ-lyase; however, MetR can induce increased HS production through this pathway. Similarly, MetR can increase the production of polyamines such as spermidine, which are involved in autophagy. In addition, MetR decreases oxidative stress by inhibiting reactive oxygen species production in mitochondria. Thus, MetR can attenuate oxidative stress through multiple mechanisms, consequently associating with lifespan extension and metabolic health. In this review, we summarize the current understanding of the effects of MetR on lifespan extension and metabolic health, focusing on the reduction in oxidative stress.
氧化应激增强与衰老及代谢健康受损密切相关，且受饮食来源的营养物质和能量影响。最近的研究表明，从酵母到啮齿动物，蛋氨酸限制（MetR）与生物体的寿命和代谢健康有关。MetR对寿命延长和代谢健康的影响部分是通过降低氧化应激来介导的。蛋氨酸代谢参与甲基供体如S-腺苷甲硫氨酸（SAM）的供应、谷胱甘肽合成和多胺代谢。SAM作为一种蛋氨酸代谢产物，激活雷帕霉素复合物1的机制靶点并抑制自噬；因此，MetR可诱导自噬。在蛋氨酸代谢的谷胱甘肽合成过程中，通过胱硫醚-β-合酶和胱硫醚-γ-裂解酶产生硫化氢（HS）；然而，MetR可通过该途径诱导HS产生增加。同样，MetR可增加多胺如亚精胺的产生，多胺参与自噬。此外，MetR通过抑制线粒体中活性氧的产生来降低氧化应激。因此，MetR可通过多种机制减轻氧化应激，从而与寿命延长和代谢健康相关。在本综述中，我们总结了目前对MetR对寿命延长和代谢健康影响的理解，重点是氧化应激的降低。
