ENERGY METABOLISM AND OXIDATIVE STRESS IN AGING

衰老过程中的能量代谢和氧化应激

• 批准号: 6775169
• 负责人: Eric Ravussin
• 金额: $ 28.1万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6775169
• 关键词: DNA damage; SDS polyacrylamide gel electrophoresis; age difference; aging; bioenergetics; blood proteins; body composition; carbohydrate metabolism; cardiovascular disorder; clinical research; free radical oxygen; gene expression; high performance liquid chromatography; human population genetics; human population study; human subject; insulin sensitivity /resistance; oxidative stress; peroxidation; photon absorptiometry; proteomics; quality of life; DNA damage; SDS polyacrylamide gel electrophoresis; age difference; aging; bioenergetics; blood proteins; body composition; carbohydrate metabolism; cardiovascular disorder; clinical research; free radical oxygen; gene expression; high performance liquid chromatography; human population genetics; human population study; human subject; insulin sensitivity /resistance; oxidative stress; peroxidation; photon absorptiometry; proteomics; quality of life

Both genetic and environmental factors play a major role in aging and the quality of life in the elderly. This project entitled "Energy Metabolism and Oxidative Stress in Aging" is part of a multi-disciplinary, multi-institutional approach to provide the fundamental knowledge that will allow the creation of preventive and compensatory interventions to improve the health of the aging population. Calorie restriction from birth or during adult life is known to prolong life in rodents and lower species alike. Calorie restriction may confer increased longevity by lowering metabolic rate and therefore reducing the oxidative damage caused by deleterious byproducts of energy metabolism called reactive oxygen species (ROS). In this project we will test whether healthy nonagenarians have a relatively low metabolic rate when compared to middle aged and young individuals and whether the low metabolic rate is associated with low levels of oxidative stress as measured by DNA damage, lipid peroxidation and protein carbonylation. Since very little is known about physical activity in very old people, we will measure it using state-of-the-art methods, i.e. doubly labeled water. The level of physical activity will be compared to the results of physical functionality assessed in Project 4 of this application with the hypothesis that these 2 parameters will be positively correlated. We will also test whether nonagenarians have unusually low levels of markers for cardiovascular disease and insulin resistance. Finally, we will determine whether nonagenarians have a particular pattern of serum proteins compared to younger groups of subjects. In this revised application, we now provide preliminary data about our ability to measure oxidative DNA damage (relationship between age and DNA oxidative damage) and proteomics (composite gel comparing the serum protein of a 92 to a 45 year old female) in old and younger subjects. Data from Project 3 will be compared to data from Projects 1, 2, 4 and 5, including genetic results, expression of genes involved in carbohydrate metabolism and stress resistance, physical functionality and cognitive functionality. Subjects will be recruited, screened and enrolled in the study over the 4 first years, and the fifth year will be used to analyze the data and write up the results.

遗传和环境因素在老年人的衰老和生活质量中都起着重要作用。该项目标题为“衰老中的能量代谢和氧化应激”是多学科的多机构方法的一部分，以提供基本知识，从而允许建立预防性和补偿性干预措施，以改善衰老人群的健康状况。 众所周知，从出生或成年生活中的卡路里限制会延长啮齿动物和较低的物种的寿命。卡路里限制可能通过降低代谢率来赋予寿命增加，从而降低由称为活性氧（ROS）的能量代谢的有害副产品造成的氧化损害。在这个项目中，我们将测试健康的非癌症与中年和年轻人相比，健康的非生产者的代谢率是否相对较低，以及低代谢率是否与通过DNA损伤，脂质过氧化和蛋白质羰基化测量的氧化应激水平低有关。由于对非常老的人的体育锻炼知之甚少，因此我们将使用最先进的方法（即双重标记的水）对其进行衡量。体育活动的水平将与本应用项目4中评估的物理功能的结果进行比较，并假设这两个参数将呈正相关。我们还将测试非癌症的心血管疾病和胰岛素抵抗的标记水平异常低。最后，我们将确定与年轻的受试者相比，非癌症是否具有特定的血清蛋白质模式。在此修订后的应用中，我们现在提供有关测量氧化性DNA损伤（年龄和DNA氧化损伤之间的关系）和蛋白质组学（比较老年人和年轻受试者的92年血清蛋白与45岁女性的血清蛋白）的初步数据。 将项目3的数据与项目1、2、4和5的数据进行比较，包括遗传结果，涉及碳水化合物代谢的基因的表达以及抗压力，身体功能和认知功能。 在第4年的研究中将招募，筛选和招募受试者，并将使用第五年来分析数据并写出结果。