Determinants of Telomere Length in Chronic SCI: A Pilot Study

慢性 SCI 端粒长度的决定因素：一项初步研究

• 批准号: 8495804
• 负责人: ERIC GARSHICK
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8495804
• 关键词: Age; Aging; Animals; Apoptosis; Base Sequence; Biological Markers; Blood; Blood specimen; Boston; C-reactive protein; Cardiopulmonary; Cardiovascular Diseases; Cardiovascular system; Caring; Cause of Death; Cell Death; Cells; Central obesity; Cessation of life; Chromosomes; Chronic; Clinical; DNA; Data; Development; Disease; Dual-Energy X-Ray Absorptiometry; Exercise; Fatty acid glycerol esters; Genetic Materials; Health; Hospitalization; Human; Human Chromosomes; Individual; Infection; Inflammation; Inflammatory; Interleukin-6; Length; Leukocytes; Life Style; Longitudinal Studies; Lung; Lung diseases; Measurement; Measures; Mediating; Molecular; Neurologic; Obesity; Outcome; Oxidative Stress; Pathogenesis; Patients; Peripheral; Persons; Physical activity; Pilot Projects; Plasma; Premature Mortality; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Heart Disease; Recurrence; Reporting; Research; Research Design; Research Support; Respiratory physiology; Risk; Risk Factors; Scanning; Severities; Skin Ulcer; Smoking; Spinal cord injury; Telomere Shortening; Testing; Therapeutic; Time; Urinary tract infection; Veterans; Work; cohort; disability; health administration; insight; mortality; novel; oxidative damage; premature; prognostic; pulmonary function; research study; respiratory; response; senescence; telomere; telomere loss

DESCRIPTION (provided by applicant): Telomeres are made up of repeat sequences of nucleotides at the ends of human chromosomes. The function of telomeres is to protect chromosomes from degradation and to maintain their structural integrity. Telomeres are analogous to a "molecular clock" reflecting the number of divisions a cell has undergone and cells with critically short telomeres are predisposed to enter senescence. Previous research suggests that telomere length is reduced in association with lifestyle and clinical factors that are common in study spinal cord injury (lac of exercise, obesity, chronic or recurrent inflammation from skin ulcers, and urinary tract infections) as well as in persons with cardiovascular and pulmonary diseases. These latter diseases are the most common causes of death in chronic spinal cord injury. By using telomere length as a molecular biomarker, it is proposed to study spinal cord injury as a disease state that promotes accelerated aging at the cellular level. It is hypothesized that greater central obesity determined by DXA scan and greater systemic inflammation assessed by plasma C-reactive protein and interleukin-6 will be associated with shorter telomere length, and that persons with shorter telomere length will have reduced pulmonary function. This pilot project will obtain preliminary data regarding these associations in 350 persons with chronic SCI, and assess longitudinal associations between systemic inflammation and telomere loss in a subset. The study of telomere length is significant since it may serve a biomarker of persons with chronic spinal cord injury most likely to develop of chronic cardiopulmonary disease and premature mortality.

描述（由申请人提供）： 端粒由人类染色体末端的核苷酸重复序列组成。端粒的功能是保护染色体免遭降解并保持其结构完整性。端粒类似于“分子钟”，反映细胞经历的分裂次数，端粒极短的细胞容易进入衰老。先前的研究表明，端粒长度的缩短与生活方式和临床因素有关，这些因素在研究脊髓损伤（缺乏运动、肥胖、皮肤溃疡引起的慢性或复发性炎症和尿路感染）以及心血管疾病患者中很常见和肺部疾病。后面这些疾病是慢性脊髓损伤最常见的死亡原因。通过使用端粒长度作为分子生物标志物，建议将脊髓损伤作为一种在细胞水平上促进加速衰老的疾病状态进行研究。据推测，通过 DXA 扫描确定的中心性肥胖程度较高以及通过血浆 C 反应蛋白和白细胞介素 6 评估的全身炎症程度较高将与较短的端粒长度相关，并且端粒长度较短的人肺功能会降低。该试点项目将获得 350 名慢性 SCI 患者中这些关联的初步数据，并评估一部分全身炎症和端粒丢失之间的纵向关联。端粒长度的研究具有重要意义，因为它可以作为慢性脊髓损伤患者最有可能发展为慢性心肺疾病和过早死亡的生物标志物。