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: 8274496
• 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/8274496
• 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

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. PUBLIC HEALTH RELEVANCE: Telomeres are a part of human chromosomes that function to protect chromosomes from damage. It has been proposed that telomeres are analogous to a molecular clock reflecting the number of divisions a cell has undergone. Cells with critically short telomeres ultimately undergo cell death. The proposed pilot study will obtain preliminary information regarding associations between reduced telomere length with greater central obesity, reduced pulmonary function, and increased blood biomarkers of systemic inflammation. It is proposed that the measurement of telomere length in persons with spinal cord injury will be a molecular biomarker that can be used to detect persons at greatest risk to develop reduced pulmonary function and cardiopulmonary diseases. This study is consistent with the Veterans Health Administration's commitment to providing longitudinal care to persons with chronic spinal cord injury and supporting research directed at understanding causes of disability and death.

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不被降解并保持其结构完整性。端粒类似于“分子钟”，反映了细胞所经历的分裂次数，端粒非常短的细胞容易进入衰老。以前的研究表明，端粒长度减少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，皮肤溃疡和尿路感染引起的慢性或复发性炎症）以及心血管和肺部疾病患者中很常见。这些疾病是慢性脊髓损伤中最常见的死亡原因。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促进细胞水平加速老化的疾病状态进行研究。据推测，DXA扫描确定的更严重的中心性肥胖以及血浆C反应蛋白和白细胞介素6评估的更严重的全身炎症将与较短的端粒长度相关，而端粒长度较短的人将具有较低的肺功能。该试点项目将获得350名慢性SCI患者的这些相关性的初步数据，并评估一个子集中全身炎症和端粒丢失之间的纵向关联。端粒长度的研究是有意义的，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。 公共卫生相关性： 端粒是人类染色体的一部分，其功能是保护染色体免受损害。有人提出端粒类似于分子钟，反映了细胞所经历的分裂次数。端粒非常短的细胞最终会经历细胞死亡。拟议的试点研究将获得关于端粒长度减少与更大的中心性肥胖，肺功能降低和全身性炎症的血液生物标志物增加之间的关联的初步信息。有人建议，在脊髓损伤的人端粒长度的测量将是一种分子生物标志物，可用于检测的人在最大的风险，发展减少肺功能和心肺疾病。这项研究符合退伍军人健康管理局的承诺，即为慢性脊髓损伤患者提供纵向护理，并支持旨在了解残疾和死亡原因的研究。