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

• 批准号: 6362231
• 负责人: RAJINDAR S SOHAL
• 金额: $ 31.24万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6362231
• 关键词: DNA damage; aging; antioxidants; cognition; dietary supplements; enzyme activity; homeostasis; hydrogen peroxide; laboratory mouse; lipid metabolism; longevity; mitochondrial DNA; mitochondrial membrane; nutrient intake activity; nutrition related tag; oxidative stress; oxidoreductase; protein metabolism; psychomotor function; respiratory function; superoxide dismutase; tissue /cell culture; transport proteins; ubiquinone

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.

本研究的主要目的是确定长期服用辅酶 Q (CoQ) 或泛醌是否会延缓或加速小鼠的衰老过程，并阐明其潜在机制。 CoQ 几乎存在于所有细胞膜的疏水内部，并具有多种功能。它最著名的是线粒体内膜电子传递系统的一个组成部分，与α-生育酚一起，它还充当抗氧化剂，抑制氧化损伤。矛盾的是，CoQ 的自动氧化也是线粒体超氧阴离子自由基的主要来源，并且产生 H2O2 的 CoQ 作为膳食补充剂被人类广泛食用，尽管长期摄入 CoQ 的影响实际上尚不清楚。长期摄入辅酶 Q 是否会导致氧化应激减弱或加剧尚未确定。本研究将阐明给小鼠施用外源 CoQ10 后生化和行为扰动的性质。待验证或反驳的具体假设是“CoQ 给药将降低氧化应激水平，改善和保护线粒体呼吸功能，增强运动和认知性能，并延长小鼠的寿命。”具体目标包括确定 CoQ 给药对以下方面的影响：(1) 小鼠的寿命； (2)与年龄相关的线粒体呼吸功能变化和氧化损伤； (3) 主要抗氧化防御之间的稳态扰动； (4) 组织匀浆中脂质、蛋白质和 DNA 氧化损伤与年龄相关； (5)小鼠认知和运动能力与年龄相关的下降。这项研究的结果将有助于了解 CoQ 摄入对小鼠衰老过程可能产生有益或有害影响的机制。