Cross‐tissue telomere length measurement to determine auxiliary marker of brain telomere length in neurosurgery patients

Abstract

BackgroundTelomere length, the length of the chromosomal endcaps, is a commonly used biomarker of health and aging, as it may indicate the extent to which cells have undergone damage. Changes in telomere length have been connected to exposure to stress and poor physical health outcomes, such as heart disease, risk of stroke, and coronary artery disease. The use of telomere length as a biomarker, therefore, is reflective of its importance in cellular development and function. As a biomarker in human studies, telomere length is measured in cells taken from blood, saliva, or other easily obtained peripheral cells, even in the study of disorders of the central nervous system (CNS) such as psychiatric illness. It is unclear if telomere length plays a role in pathophysiological processes in the brain. This question could be better addressed by determining if telomere length changes in the CNS are commensurate with those in peripheral tissues.MethodsIn this study, we aim to look at the relationship between CNS neural telomere length measurements in comparison to peripheral measurements in two different tissue types to determine if peripheral telomere length measurements may be proxies for CNS measures. Samples of blood, saliva, and brain were taken in 22 neurosurgery patients before, during, and after surgery. Brain resection surgeries were performed to remove tissue at seizure focal points. Patients had an average age of 32.4 years ranging from 5 to 61 years old and 15 out of 22 patients (68%) were male. Telomere length was measured in all samples using quantitative PCR techniques.ResultsBlood telomere length, but not saliva or brain, negatively correlated with age (r=0.84, p<0.001), a previously reported phenomenon. Comparing pre‐ and post‐surgery samples, we found that saliva telomere length had a trend decrease (paired student's t‐test, p=0.08), while blood telomere length had no change. Intriguingly, we found a trend correlation between brain telomere length and pre‐surgery saliva telomere length (standardized beta = 0.47, r=0.47, p=0.09).ConclusionsWe found that telomere measures in saliva trended to be different before and after surgery, in which a significant intervening variable was use of synthetic glucocorticoids to prevent edema. We hypothesize that exposure to glucocorticoid even on this acute time course may affect saliva telomere length. Further, we have found that there may exist a relationship between brain and pre‐surgery salivary telomere length, but no other examined tissues (post‐surgery saliva, pre‐surgery blood, and post‐surgery blood). These findings may help to identify saliva telomere length as a potential correlate for brain telomere length, which may broaden its applications as a biomarker.Support or Funding InformationUniversity of Iowa CPH Advancing Graduate Student Success Award