Determinants of Telomere Length in Chronic SCI: A Pilot Study

描述(由申请人提供)： 端粒是由人类染色体末端的核苷酸重复序列组成的。端粒的功能是保护染色体不被降解，并保持其结构的完整性。端粒类似于反映细胞分裂次数的“分子钟”，端粒极短的细胞容易进入衰老。先前的研究表明，端粒长度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、慢性或复发性皮肤溃疡和尿路感染)以及患有心血管和肺部疾病的人中很常见。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，有人建议在细胞水平上将脊髓损伤作为一种促进加速衰老的疾病状态来研究。据推测，DXA扫描确定的中心性肥胖程度越大，血浆C-反应蛋白和白细胞介素6评估的全身炎症程度越高，端粒长度越短，端粒长度越短的人肺功能就越差。这项试点项目将获得350名慢性脊髓损伤患者中有关这些相关性的初步数据，并在子集中评估全身炎症和端粒丢失之间的纵向相关性。端粒长度的研究意义重大，因为它可以作为慢性脊髓损伤患者的生物标记物，最有可能发展为慢性心肺疾病和过早死亡。

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.