Weight Loss & Exercise Effects on Telomere Length in Postmenopausal Women

减肥

• 批准号: 8206548
• 负责人: Anne M. McTiernan
• 金额: $ 18.65万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-14 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206548
• 关键词: Aerobic Exercise; Affect; Aging; Alleles; Base Pairing; Base Sequence; Behavioral; Biological; Biological Markers; Bladder; Blood Cells; Blood specimen; Body Composition; Body Weight; Body Weight Changes; Body Weight decreased; Body fat; Body mass index; Breast; C-reactive protein; Calories; Cell Aging; Cell division; Cells; Chemoprevention; Chromosomal Instability; Chromosomes; Chronic Disease; Colon; Comet Assay; DEXA; DNA; DNA Repair; DNA Structure; Data; Development; Diet; Dietary Fats; Endometrium; Epidemiologic Studies; Estradiol; Estrogens; Estrone; Exercise; Expenditure; Fasting; Fatty acid glycerol esters; Gene Dosage; Genes; Genetic Polymorphism; Genetic Recombination; Genotype; Glucose; Goals; Gonadal Steroid Hormones; Head and neck structure; Human; Inflammation; Inflammatory; Insulin; Insulin Resistance; Insulin-Like Growth-Factor Binding Protein 1; Interleukin-6; Intervention; Kidney; Lead; Length; Leptin; Leukocytes; Life Style; Link; Lung; Malignant Neoplasms; Measures; Methods; Modification; Molecular; Nucleic acid sequencing; Obesity; Observational Study; Outcome; Overweight; Parents; Pathway interactions; Peripheral; Physical activity; Postmenopause; Proteins; Randomized; Relative (related person); Research; Resources; Risk; Sampling; Serum; Serum amyloid A protein; Somatic Cell; Somatomedins; Structure; TERF1 gene; TERT gene; TNKS gene; Techniques; Telomere Shortening; Testing; Testosterone; Weight; Weight Gain; Woman; Work; adipokines; adiponectin; aged; arm; base; cancer prevention; cancer risk; cancer type; diabetes prevention program; diet and exercise; energy balance; experience; ghrelin; inflammatory marker; intervention effect; lifestyle factors; men; mimetics; novel; programs; public health relevance; randomized trial; response; sedentary; senescence; steroid hormone; telomere; weight loss intervention

DESCRIPTION (provided by applicant): Overweight, obesity, and a sedentary lifestyle increase risk for several types of cancer. Currently, little is known about the effects of lifestyle change at the cellular level in humans. The telomeric regions of chromosomes comprise the molecular caps or ends of the chromosomes. Progressive telomere shortening of somatic cells with successive cell division is a hallmark of cellular aging, with loss of ~ 50-100 base pairs per cell division. Recent epidemiologic studies have suggested an association between telomere shortening in peripheral blood cells and increased risk of several cancers. Observational data suggests that overweight and obesity are associated with telomere shortening, but there is a lack of research on 1) the independent and combined effects of dietary weight loss and exercise on telomere length and 2) the amount of weight loss, or change in body composition that may be necessary to effect changes in telomere length. We propose to investigate within a completed randomized trial the independent and combined effects of dietary weight loss, exercise, and the two combined, compared with controls, on leukocyte telomere length (T/S ratio) measured in samples collected at baseline and 12 months in 438 postmenopausal, overweight/obese, sedentary women aged 50-75 years. Women were randomized to reduced calorie weight loss "diet-only" that achieved a mean 9.9% loss of baseline weight (N=118); 2) moderate intensity aerobic exercise (225 min/wk) intervention "exercise-only" that produced a mean 2.6% weight loss (N=117); 3) both interventions "diet+exercise" with mean 11.6% weight loss (N=116); and 4) control (0.7% weight loss) (N=87). The weight loss program was a group-based modification of the Diabetes Prevention Program lifestyle change weight loss program, and included goals of 500-1000 kcal/day reduction, dietary fat < 25% of calories, goal 10% weight loss in first 6 months, and behavioral change techniques. Mean exercise over 12 months was 83% of goal 225 minutes/week in the 2 exercise groups. Attrition was 9%. Primary analyses will be intent-to-treat of intervention effect on telomere shortening. The primary endpoint will be changes in relative telomere length of leukocyte DNA. Additional analyses will be correlational, investigating associations between telomere length and other analytes already measured in the trial: DNA damage repair (COMET), sex hormones, insulin & glucose, inflammation (C-reactive protein, serum amyloid A, interleukin-6), insulin like growth factor 1 and binding protein 3, and adipokines (adiponectin, leptin). Effect modification by gene SNP alleles related to telomere length (TERT, TRF1, TNKS1, TRF2, RAP1, POT1, and rs12696304 near TERC) will also be tested. The proposed research is highly novel, and takes advantage of an existing resource of stored DNA from a completed trial. If weight loss or exercise reduces telomere shortening, it will provide additional clues to the links between these lifestyle factors and risks for cancer and other chronic diseases that have been associated with telomere length. PUBLIC HEALTH RELEVANCE: This project will investigate the effects of physical activity, reduced-calorie weight loss and the combination of these two interventions, on the length of telomeres, which is a part of DNA. Shorter telomeres have been linked to cancer risk. The project includes 438 postmenopausal, overweight/obese, sedentary women who have already completed the trial from which blood samples will be used.

描述（由申请人提供）：超重、肥胖和久坐的生活方式会增加患多种癌症的风险。目前，人们对生活方式改变对人类细胞水平的影响知之甚少。染色体的端粒区域包含染色体的分子帽或末端。随着连续细胞分裂，体细胞的端粒逐渐缩短是细胞衰老的标志，每次细胞分裂会损失约 50-100 个碱基对。最近的流行病学研究表明，外周血细胞端粒缩短与多种癌症风险增加之间存在关联。观察数据表明，超重和肥胖与端粒缩短有关，但缺乏以下方面的研究：1）饮食减肥和运动对端粒长度的独立影响和综合影响；2）体重减轻量或身体成分的变化可能是影响端粒长度变化所必需的。我们建议在一项已完成的随机试验中调查饮食减肥、运动以及两者相结合对白细胞端粒长度（T/S 比）的独立影响和综合影响（与对照相比），这些影响是在 438 名 50-75 岁绝经后、超重/肥胖、久坐的女性中收集的基线和 12 个月样本中测量的。女性被随机分配到“仅通过饮食”减少热量的减肥组，基线体重平均减轻了 9.9%（N=118）； 2) 中等强度有氧运动（225 分钟/周）干预“仅运动”，平均体重减轻 2.6%（N=117）； 3) 两种干预措施“饮食+运动”平均减重 11.6% (N=116)； 4) 对照（体重减轻 0.7%）（N=87）。该减肥计划是对糖尿病预防计划生活方式改变减肥计划进行的基于小组的修改，包括每天减少 500-1000 kcal 的目标、饮食脂肪<卡路里的 25%、前 6 个月内体重减轻 10% 的目标以及行为改变技术。 2 个锻炼组 12 个月内的平均锻炼量为每周 225 分钟目标的 83%。员工流失率为 9%。主要分析将是针对端粒缩短的干预效果的意向治疗。主要终点是白细胞 DNA 相对端粒长度的变化。其他分析将是相关性的，调查端粒长度与试验中已测量的其他分析物之间的关联：DNA损伤修复（COMET）、性激素、胰岛素和葡萄糖、炎症（C反应蛋白、血清淀粉样蛋白A、白细胞介素6）、胰岛素样生长因子1和结合蛋白3以及脂肪因子（脂联素、瘦素）。还将测试与端粒长度相关的基因 SNP 等位基因（TERT、TRF1、TNKS1、TRF2、RAP1、POT1 和 TERC 附近的 rs12696304）的效果修饰。拟议的研究非常新颖，并且利用了已完成试验中存储的 DNA 的现有资源。如果减肥或运动减少端粒缩短，它将为这些生活方式因素与癌症和其他与端粒长度相关的慢性疾病风险之间的联系提供更多线索。 公共健康相关性：该项目将研究体力活动、低热量减肥以及这两种干预措施的结合对端粒长度（DNA 的一部分）的影响。较短的端粒与癌症风险有关。该项目包括 438 名绝经后、超重/肥胖、久坐的女性，她们已经完成了将使用血液样本的试验。