Hipkiss Alan R
Centre for Experimental Therapeutics, William Harvey Research Institute, Barts' and the London Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London, EC1 6BQ, UK.
Biogerontology. 2007 Apr;8(2):221-4. doi: 10.1007/s10522-006-9034-x. Epub 2006 Sep 13.
The possibility is discussed that dietary restriction modulates ageing and onset of related pathologies by, in addition to upregulation of proteolysis, suppression of glycolysis which in turn decreases generation of methylglyoxal (MG), a highly toxic glycating agent which can provoke cellular senescence and many age-related pathologies. This proposal is supported by the observation that intermittent feeding can mimic dietary restriction's effects on mouse lifespan without any overall reduction in calorie intake. That MG-induced modification of the chaperone and anti-apoptotic protein (Hsp27) increases its protective functions suggests a possible hormetic response to transient MG production during transient periods of glycolysis in dietary restricted animals. It is suggested that in the ad libitum-fed state permanent glycolysis would suppress proteolysis and continuously generate MG which overwhelms the anti-MG defence systems. It is proposed that periods of fasting might be a more acceptable approach than permanent undernutrition in our attempts to slow human ageing, although timing of meals may prove important.
本文讨论了一种可能性，即饮食限制除了上调蛋白水解作用外，还通过抑制糖酵解来调节衰老及相关病理状态的发生，糖酵解的抑制进而减少了甲基乙二醛（MG）的生成，MG是一种剧毒的糖化剂，可引发细胞衰老和许多与年龄相关的病理状态。间歇性喂食可模拟饮食限制对小鼠寿命的影响，而不会使卡路里摄入量总体减少，这一观察结果支持了上述观点。MG对伴侣蛋白和抗凋亡蛋白（Hsp27）的修饰增加了其保护功能，这表明在饮食限制的动物中，糖酵解短暂时期内对短暂产生的MG可能存在一种适应性反应。有人认为，在自由进食状态下，持续的糖酵解会抑制蛋白水解作用，并持续产生MG，从而使抗MG防御系统不堪重负。有人提出，在我们试图减缓人类衰老的过程中，禁食期可能比长期营养不良更易接受，不过进餐时间可能也很重要。
