Stress, Mood, Omega-3 Fatty Acids, & Telomeric Aging: Randomized Controlled Trial

压力、情绪、Omega-3 脂肪酸、

• 批准号: 8129094
• 负责人: JANICE KIECOLT-GLASER
• 金额: $ 26.52万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8129094
• 关键词: Acids; Acute; Address; Affect; Aftercare; Aging; Aging-Related Process; Basic Science; Blood; Cell Aging; Cells; Chromosomal Stability; Chromosomes; Clinical; Coronary heart disease; Data; Diet; Dietary Intervention; Disease; Dose; Double-Blind Method; Eicosapentaenoic Acid; Enzymes; Funding; Health; Health behavior; Individual; Inflammation; Inflammatory Response; Intervention; Laboratories; Length; Leukocytes; Life Style; Link; Literature; Maintenance; Measures; Mediating; Moods; N-3 polyunsaturated fatty acid; Omega-3 Fatty Acids; Oxidative Stress; Parents; Patients; Placebo Control; Placebos; Plasma; Polyunsaturated Fatty Acids; Prospective Studies; Psychological Stress; Randomized Controlled Trials; Relative (related person); Reporting; Research Personnel; Sampling; Stress; Supplementation; Telomerase; Telomere Capping; Telomere Shortening; Testing; Time; acute stress; age related; biological adaptation to stress; cell age; clinically significant; cost; cytokine; depressive symptoms; innovation; mortality; novel; primary outcome; programs; psychological distress; response; restoration; stressor; success; telomere

DESCRIPTION (provided by applicant): Telomeres are important for chromosomal stability and replication, and the enzyme telomerase is important for telomere formation, maintenance, and restoration. Telomerase activity and telomere length, cell aging measures, have clinical significance for health: a growing literature has linked lower levels of telomerase activity and shorter telomeres with health behaviors, age-related diseases, and mortality. Inflammation and oxidative stress accelerate telomere shortening; oxidative stress promotes telomere erosion during cellular replication, and inflammation enhances the leukocyte turnover rate. The omega-3 (n-3) polyunsaturated fatty acids (PUFAs) can reduce inflammation and decrease oxidative stress. Accordingly, by adding cell aging studies to an ongoing NIA-funded double-blind, placebo-controlled randomized controlled trial (RCT) that addresses the impact of n-3 PUFA supplementation on inflammation and mood (R01 AG029562), this study will assess the impact of diet-related reductions in inflammation and oxidative stress on telomerase activity and leukocyte telomere length. Key preliminary data from the collaborating UCSF and OSU laboratories support both the relevance and likelihood of success. UCSF's recent large prospective study with stable coronary heart disease patients demonstrated that higher baseline n-3 PUFA levels were associated with slower telomere attrition 5 years later, and another UCSF study showed increased telomerase activity following a 3-month intervention, providing a reasonable mechanism. In accord with this finding, preliminary collaborative OSU/UCSF data from the OSU n-3 RCT show that individuals receiving n-3 supplementation had longer telomeres at the end of the four-month trial, in contrast to modest telomere shortening observed among placebo subjects, producing a significant group by time interaction. Thus, the proposed study will assess the impact of a simple dietary intervention on the cell aging process. Further, it will test specific mechanisms such as whether the n-3 PUFAs reduce cell aging through alterations in proinflammatory cytokines and/or oxidative stress. In short, the addition of cell aging assessments to the OSU RCT will leverage our well-characterized sample to simultaneously address important and innovative basic science and clinical health questions. Our primary aim is: (1) To assess the impact of n-3 PUFA supplementation on changes in telomerase activity, and secondarily, in telomere length, as well as the relationship of these changes to n-3 dose. Secondary Aims: (2) To determine if changes in proinflammatory cytokines and oxidative stress mediate the effect of n-3 supplementation on cell aging; (3) to replicate and extend prior reports of cross-sectional relationships between telomerase activity and telomere length with proinflammatory cytokines and depressive symptoms; and (4) To replicate recent evidence showing that a laboratory stressor increases telomerase responsivity, and to explore how telomerase responsivity to acute stress may be altered by n-3 supplementation. PUBLIC HEALTH RELEVANCE: Telomerase activity and telomere length, cell aging measures, have clinical significance for health. Lower levels of telomerase activity and shorter telomeres are associated with aging, age-related diseases, and mortality. Preliminary data suggest that higher blood levels of omega-3 fatty acids may serve to slow age- related telomere attrition. By adding cell aging assessments to an ongoing randomized controlled trial of omega-3 supplementation, we can assess how omega-3 supplementation affects both telomerase activity and telomere length, as well as possible mechanisms.

描述（由申请人提供）：端粒对染色体稳定性和复制很重要，端粒酶对端粒的形成、维持和恢复很重要。端粒酶活性和端粒长度，细胞衰老的措施，对健康有临床意义：越来越多的文献将较低水平的端粒酶活性和较短的端粒与健康行为，年龄相关疾病和死亡率联系起来。炎症和氧化应激加速端粒缩短;氧化应激促进细胞复制期间的端粒侵蚀，并且炎症增强白细胞更新率。omega-3（n-3）多不饱和脂肪酸（PUFA）可以减少炎症和减少氧化应激。因此，通过将细胞衰老研究添加到正在进行的NIA资助的双盲，安慰剂对照的随机对照试验（RCT）中，该试验解决了n-3 PUFA补充剂对炎症和情绪的影响（R 01 AG 029562），该研究将评估饮食相关的炎症和氧化应激减少对端粒酶活性和白细胞端粒长度的影响。来自UCSF和OSU合作实验室的关键初步数据支持成功的相关性和可能性。UCSF最近对稳定型冠心病患者进行的大型前瞻性研究表明，较高的基线n-3 PUFA水平与5年后端粒磨损较慢有关，另一项UCSF研究显示，在3个月的干预后端粒酶活性增加，提供了合理的机制。与这一发现雅阁，来自OSU n-3 RCT的初步合作OSU/UCSF数据显示，在4个月的试验结束时，接受n-3补充剂的个体具有较长的端粒，与安慰剂受试者中观察到的适度端粒缩短相反，产生了显著的组与时间的相互作用。因此，拟议的研究将评估简单的饮食干预对细胞衰老过程的影响。此外，它将测试特定的机制，例如n-3 PUFA是否通过改变促炎细胞因子和/或氧化应激来减少细胞衰老。简而言之，在俄勒冈州立大学随机对照试验中增加细胞衰老评估将利用我们充分表征的样本，同时解决重要和创新的基础科学和临床健康问题。我们的主要目标是：（1）评估补充n-3 PUFA对端粒酶活性变化的影响，其次是端粒长度的变化，以及这些变化与n-3剂量的关系。次要目标：（2）确定促炎细胞因子和氧化应激的变化是否介导了n-3补充对细胞衰老的影响;（3）复制和扩展先前关于端粒酶活性和端粒长度与促炎细胞因子和抑郁症状之间的横截面关系的报道;和（4）为了复制最近的证据表明实验室应激物增加端粒酶反应性，并探索端粒酶对急性应激的反应性如何通过补充N-3而改变。 公共卫生相关性：端粒酶活性和端粒长度，细胞衰老的措施，对健康有临床意义。较低水平的端粒酶活性和较短的端粒与衰老、年龄相关疾病和死亡率有关。初步数据表明，血液中较高的ω-3脂肪酸水平可能有助于减缓与年龄相关的端粒磨损。通过将细胞衰老评估添加到正在进行的omega-3补充剂随机对照试验中，我们可以评估omega-3补充剂如何影响端粒酶活性和端粒长度，以及可能的机制。