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.
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.
