Hyun Dong-Hoon, Hernandez Joe O, Mattson Mark P, de Cabo Rafael
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Ageing Res Rev. 2006 May;5(2):209-20. doi: 10.1016/j.arr.2006.03.005. Epub 2006 May 11.
Oxidative stress over time leads to the accumulation of damaged macromolecules and to profound physiological changes that are associated with several age-related diseases. The plasma membrane redox system (PMRS) appears to attenuate oxidative stress acting as a compensatory mechanism during the aging process. The PMRS appears to play a protective role during mitochondrial dysfunction to provide cells with a survival mechanism by lowering oxidative stress. The PMRS accomplishes this by producing more NAD(+) for glycolytic ATP production via transfer of electrons from intracellular reducing equivalents to extracelluar acceptors. Ubiquinone and alpha-tocopherol are key antioxidant molecules in the plasma membrane that are affected by aging and can be up-regulated by dietary interventions such as calorie restriction (CR). Up-regulation of PMRS activity leads to cell survival and membrane homeostasis under stress conditions and during calorie restriction. Further studies of the PMRS may provide not only additional information on the mechanisms involved in aging and CR, but may provide therapeutic targets for the prevention and treatment of age-related diseases.
随着时间的推移，氧化应激会导致受损大分子的积累以及与多种年龄相关疾病相关的深刻生理变化。质膜氧化还原系统（PMRS）似乎作为衰老过程中的一种补偿机制，减弱氧化应激。在线粒体功能障碍期间，PMRS似乎发挥保护作用，通过降低氧化应激为细胞提供一种生存机制。PMRS通过将细胞内还原当量的电子转移到细胞外受体，产生更多的NAD⁺用于糖酵解ATP的产生，从而实现这一点。泛醌和α-生育酚是质膜中的关键抗氧化分子，它们会受到衰老的影响，并且可以通过诸如热量限制（CR）等饮食干预上调。在应激条件下和热量限制期间，PMRS活性的上调会导致细胞存活和膜稳态。对PMRS的进一步研究不仅可能提供有关衰老和CR所涉及机制的更多信息，还可能为预防和治疗年龄相关疾病提供治疗靶点。
