Hipkiss Alan R
Centre for Experimental Therapeutics, William Harvey Research Institute, Barts' and the London School of Medicine and Dentistry, UK.
Ann N Y Acad Sci. 2006 May;1067:361-8. doi: 10.1196/annals.1354.051.
The mechanisms by which dietary restriction (DR) suppresses aging are not understood. Suppression of glycolysis by DR could contribute to controlling senescence. Many glycolytic intermediates can glycate proteins and other macromolecules. Methyglyoxal (MG), formed from dihydroxyacetone- and glyceraldehyde-3-phosphates, rapidly glycates proteins, damages mitochondria, and induces a prooxidant state to create a senescent-like condition. Ad libitum-fed and DR animals differ in mitochondrial activity and glycolytic flux rates. Persistent glycolysis in the unrestricted condition would increase the intracellular load of glycating agents (e.g., MG) and increase ROS generation by inactive mitochondria. Occasional glycolysis during DR would decrease MG and reactive oxygen species (ROS) production and could be hormetic, inducing synthesis of glyoxalase-1 and anti-glycating agents (carnosine and polyamines).
饮食限制（DR）抑制衰老的机制尚不清楚。DR对糖酵解的抑制可能有助于控制衰老。许多糖酵解中间产物可使蛋白质和其他大分子发生糖基化。由二羟基丙酮磷酸和3-磷酸甘油醛形成的甲基乙二醛（MG）能迅速使蛋白质糖基化，损害线粒体，并诱导促氧化状态以产生类似衰老的状况。随意进食和DR处理的动物在线粒体活性和糖酵解通量率方面存在差异。在不受限制的条件下持续进行糖酵解会增加细胞内糖基化剂（如MG）的负荷，并增加无活性线粒体产生的活性氧（ROS）。DR期间偶尔进行糖酵解会减少MG和活性氧的产生，并且可能具有 hormetic 效应，诱导乙二醛酶-1以及抗糖基化剂（肌肽和多胺）的合成。
