PROTON LEAK, OXIDATIVE STRESS, AND ENERGY RESTRICTION

描述（改编自研究者摘要）：CR的机制 在多种啮齿类动物中延长寿命的作用具有高度相关性， 对衰老研究的重要性。线粒体不能无缝地将 线粒体膜电位对化学能，即ATP的转化。相反， 质子通过线粒体内部“泄漏”的几种可能性 膜不需要通过ATP酶和ATP的合成通道。 研究者提出假设，认为这实际上是比率， 这些泄漏反应的程度都是1）休息的主要贡献者 线粒体O2消耗，和2）生产的主要贡献者， 活性氧簇（ROS）。热量限制已经被证明 不断地增加寿命，并减少几种生化 线粒体和氧化应激的终点，特别是在有丝分裂后 组织中前提是热量限制（CR），甲状腺功能减退， 膳食脂肪的调节将降低线粒体通透性（即质子渗透性 泄漏），从而减少分子氧消耗，并推测 氧化应激

DESCRIPTION (adapted from Investigator's abstract): The mechanism by which CR works to extend lifespan in multiple rodent species is of high relevance and significance to research into aging. Mitochondria do not seamlessly convert the mitochondrial membrane potential to chemical energy, i.e. ATP. Rather there are several possibilities for proton "leak" through the mitochondrial inner membrane that do not require passage through the ATPase and synthesis of ATP. The investigator formulates the hypothesis that it is really the rate and extent of these leak reactions that are both 1) major contributors to resting mitochondrial O2 consumption, and 2) major contributors to the production of reactive oxygen species (ROS). Caloric Restriction has been demonstrated consistently to increase lifespan, and to decrease several biochemical endpoints of mitochondrial and oxidative stress specifically in postmitotic tissues. The premise is that Caloric Restriction (CR), hypothyroidism, and modulation of dietary fat will decrease mitochondrial permeability (i.e. proton leak), therefore decreasing molecular Oxygen consumption, and presumably oxidative stress.