COENZYME Q INTAKE, OXIDATIVE STRESS, AND AGING IN MICE

小鼠的辅酶 Q 摄入量、氧化应激和衰老

基本信息

批准号：
6756547
负责人：
RAJINDAR S SOHAL
金额：
$ 32.8万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-03-01 至 2007-05-31
项目状态：
已结题

项目摘要

The main purpose of this study is to determine whether the long-term administration of co-enzyme Q (CoQ) , or ubiquinone, retards or accelerates the aging process in mice and to elucidate the underlying mechanisms. CoQ is present in the hydrophobic interior of virtually all the cellular membranes and has versatile functions. It is best known as a component of the electron transport system in the inner mitochondrial membrane, where, in concert with alpha-tocopherol, it also acts as an antioxidant, inhibiting oxidative damage. Paradoxically, auto-oxidation of CoQ is also the main source of mitochondrial superoxide anion radical and H2O2 generation CoQ is being widely consumed by humans as a dietary supplement, even though the effects of long-term intake of CoQ are virtually unknown. Whether the long-term intake of CoQ leads to an attenuation or an exacerbation of oxidative stress has not been determine. The present study will elucidate the nature of biochemical and behavioral perturbations following the administration of exogenous CoQ10 to mice. The specific hypothesis to be validated or refuted is that "CoQ administration will decrease the level of oxidative stress, improve and preserve mitochondrial respiratory functions, enhance motor and cognitive performance, and extend life span of mice." Specific Aims include determination of the effects of CoQ administration on: (1) the longevity of mice; (2) age-associated changes in mitochondrial respiratory functions and oxidative damage; (3) perturbations of homeostasis among the main anti-oxidative defenses; (4) age-related accrual of oxidative damage to lipids, proteins and DNA in tissue homogenates; and (5) age-associated decline in cognitive and motor abilities of the mice. Results of this study will provide an understanding of the mechanisms by which CoQ intake may have a beneficial or deleterious effect on the aging process in mice.

这项研究的主要目的是确定共同酶Q（COQ）或泛氨基酮的长期施用是否阻碍或加速小鼠的衰老过程并阐明基本机制。 COQ存在于几乎所有细胞膜的疏水内部中，并且具有多功能功能。它是内部线粒体膜中电子传输系统的组成部分的最著名的，在该膜中，它与α-生育酚一起协同起作用，也充当抗氧化剂，抑制氧化损伤。矛盾的是，COQ的自身氧化也是线粒体超氧化物阴离子自由基和H2O2 Generation CoQ的主要来源，即使人类长期摄入COQ的效果实际上是未知的，即使人类作为饮食补充剂被广泛消费。 COQ的长期摄入量是否导致衰减或氧化应激加剧。本研究将阐明外源性COQ10向小鼠施用后的生化和行为扰动的性质。要验证或驳斥的具体假设是“ COQ给药将降低氧化应激水平，改善和保留线粒体呼吸功能，增强运动和认知性能，并延长小鼠的寿命。”具体目的包括确定COQ给药对以下原因的影响：（1）小鼠的寿命；（2）与年龄相关的线粒体呼吸功能和氧化损伤的变化；（3）主要抗氧化防御措施之间稳态的扰动；（4）组织匀浆中脂质，蛋白质和DNA的氧化损伤的应计；（5）小鼠认知和运动能力的年龄相关。这项研究的结果将对COQ摄入可能对小鼠的衰老过程产生有益或有害影响的机制有一种理解。