PROTON LEAK, OXIDATIVE STRESS, AND ENERGY RESTRICTION

描述(改编自调查者摘要)：CR 在多种啮齿动物中延长寿命的工作具有很高的相关性和 对衰老研究的意义。线粒体不会无缝地将 线粒体膜电位转化为化学能，即三磷酸腺苷。相反，有一些 质子通过线粒体内部“泄漏”的几种可能性 不需要通过ATPase和合成ATP的膜。 研究人员提出了这样的假设，即它确实是速度和 这些泄漏反应的程度都是1)休息的主要因素 线粒体O2消耗，以及2)主要贡献者产生 活性氧(ROS)。卡路里限制已被证明 始终如一地延长寿命，减少几种生化 线粒体和氧化应激的终点在有丝分裂后特异 纸巾。前提是卡路里限制(CR)、甲状腺功能减退和 膳食脂肪的调节会降低线粒体的通透性(即质子 泄漏)，因此减少了分子氧消耗，并可能 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.