S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects.
S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects.
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在大多数模式生物中，蛋氨酸限制(METR)可以延长寿命并延缓衰老相关病理的发生。在此之前，我们已经证明，添加代谢物S-腺苷-L-同型半胱氨酸可以延长酿酒酵母芽生酵母的寿命，并激活能量传感器AMP激活的蛋白激酶。然而，其中涉及的机制以及SAH是否可以延长后生动物的寿命仍不清楚。在这里，我们表明SAH补充降低了蛋氨酸水平，并概括了甲氨蝶呤的许多生理和分子效应。在酵母中，补充SAH导致雷帕霉素复合体1(TORC1)靶标的抑制和自噬的激活。此外，在秀丽隐杆线虫中，SAH治疗通过激活AMPK和提供Metr的好处来延长寿命。因此，我们建议SAH可以作为一种干预措施来降低细胞内Met，并赋予Metr好处。描述SAH如何延长寿命的模型。SAH的摄入减少了细胞内的蛋氨酸，并在酵母和线虫中诱导了与甲氨蝶呤相关的益处。SAH治疗通过抑制mTORC1、激活自噬和AMPK来延长寿命。
Methionine restriction (MetR) can extend lifespan and delay the onset of aging‐associated pathologies in most model organisms. Previously, we showed that supplementation with the metabolite S‐adenosyl‐L‐homocysteine (SAH) extends lifespan and activates the energy sensor AMP‐activated protein kinase (AMPK) in the budding yeast Saccharomyces cerevisiae. However, the mechanism involved and whether SAH can extend metazoan lifespan have remained unknown. Here, we show that SAH supplementation reduces Met levels and recapitulates many physiological and molecular effects of MetR. In yeast, SAH supplementation leads to inhibition of the target of rapamycin complex 1 (TORC1) and activation of autophagy. Furthermore, in Caenorhabditis elegans SAH treatment extends lifespan by activating AMPK and providing benefits of MetR. Therefore, we propose that SAH can be used as an intervention to lower intracellular Met and confer benefits of MetR. A model depicting how SAH extends lifespan. The intake of SAH reduces intracellular Met and induces benefits associated with MetR in yeast and nematodes. SAH treatment extended lifespan via inhibition of mTORC1 and activation of autophagy and AMPK.
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影响因子：
32.4
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