a Departamento de Bioquímica y Biología Molecular, Facultad de Medicina , Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo , Oviedo , Spain.
b Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) , Madrid , Spain.
Autophagy. 2019 Mar;15(3):558-559. doi: 10.1080/15548627.2018.1533059. Epub 2018 Oct 18.
Methionine restriction, i.e., a partial depletion of the essential sulfur amino acid methionine from nutrition, extends lifespan in model organisms including yeast, nematodes, mice and rats. Recent results indicate that this strategy also prolongs health span and longevity in 2 short-lived strains of mice (with the Lmna or zmpste24 genotypes) that represent animal models of Hutchinson-Gilford progeria syndrome (HGPS). The beneficial effects of methionine restriction on HGPS could be linked to reduced inflammation, and improved DNA stability, as well as the normalization of lipid and bile acid metabolism. Previous work has established that behavioral, nutritional, pharmacological and genetic manipulations that extend longevity in model organisms are only efficient if they induce increased autophagic flux. Methionine restriction extends lifespan in Saccharomyces cerevisiae in an Atg5- and Atg7-dependent fashion, supporting the notion that methionine restriction may indeed mediate its antiaging effects through the induction of macroautophagy/autophagy as well. Based on these findings, we speculate that autophagy might constitute an actionable therapeutic target to treat progeroid syndromes.
蛋氨酸限制，即营养中必需的含硫氨基酸蛋氨酸的部分耗尽，可延长酵母、线虫、小鼠和大鼠等模式生物的寿命。最近的研究结果表明，这种策略也可以延长两种寿命较短的小鼠（具有 Lmna 或 zmpste24 基因型）的健康跨度和寿命，这两种小鼠代表亨廷顿病性进行性肌阵挛震颤综合征（HGPS）的动物模型。蛋氨酸限制对 HGPS 的有益影响可能与炎症减少、DNA 稳定性提高以及脂质和胆汁酸代谢的正常化有关。以前的工作已经证明，如果能够诱导自噬通量增加，那么延长模式生物寿命的行为、营养、药理和遗传操作才是有效的。蛋氨酸限制以依赖 Atg5 和 Atg7 的方式延长酿酒酵母的寿命，这支持了这样一种观点，即蛋氨酸限制可能确实通过诱导巨自噬/自噬来介导其抗衰老作用。基于这些发现，我们推测自噬可能成为治疗进行性疾病综合征的可行治疗靶点。
