Changes in Telomere Length and Indicators of Oxidative Stress in Critically Ill Mechanically Ventilated Adults - A Pilot Study.

Abstract

Background: Telomeres are structures at the end of chromosomes that shorten with each cell division. The purpose of this pilot project is to report changes in telomere length (T/S ratio), indicators of oxidative stress (serum protein carbonyl, vitamin C, GSH:GSSG, and total antioxidant capacity) from Intensive Care Unit (ICU) admission to ICU discharge, and to explore their association with ICU-related morbidities among critically ill mechanically ventilated adults.

Methods: Blood was collected from mechanically ventilated patients (n = 25) at enrollment and within 48 hours of ICU discharge. Telomere length from peripheral blood mononuclear cells (PBMCs) was determined using RTqPCR. ELISAs were used to measure indicators of oxidative stress. Descriptive analysis, paired t-tests, and Pearson's correlations were performed.

Results: Mean age was 62.0 ± 12.3 years, 28.6% were male, and 76.2% were White with disease severity using APACHE III (74.6 ± 24.6) and SOFA (7.6 ± 3.2). Mean T/S ratios shortened (ICU: 0.712, post-ICU: 0.683, p < 0.001, n = 19) and serum protein carbonyl increased (ICU: 7437 nmol/mg ± 3328, post-ICU: 10,254 nmol/mg ± 3962, p < 0.005) as did the oxidative stress index (protein carbonyl/GSH:GSSG, ICU: 1049.972 ± 420.923, post-ICU: 1348.971 ± 417.175, p = 0.0104). T/S ratio was positively associated with APACHE III scores (ICU: r = 0.474, post-ICU: r = 0.628, p < 0.05).

Conclusions: Pilot findings suggest that critical illness significantly correlates with telomere attrition, perhaps due to increased oxidative stress. Future larger and longitudinal studies investigating mechanisms of telomere attrition and associations with clinical outcomes are needed to identify potential modifiable factors for subsequent intervention to improve outcomes for critically ill patients.