Mitochondrial DNA damage is associated with earlier ventilatory threshold in military veterans with unexplained fatigue

Abstract

Exercise intolerance and post‐exertion fatigueare common symptoms of individuals with mitochondrial dysfunction, and have recently been reported in veterans with unexplained fatigue. The goal of the present study was to assess direct (mtDNA damage) and indirect (cardiopulmonary exercise) measures of mitochondrial dysfunction in fatigued veterans. Twenty‐two(50.0±4.9 years) male veterans volunteered for this study. Each veteran completed general health questionnaire including following items: physical fatigue (44.7±13.8; Fatigue Severity Scale), physical activity questionnaire (1026.4±998.9 MET·min·wk−1), and smoking history (pack years 10.0±13.0). Each veteran provided peripheral blood mononuclear cells for total DNA extraction and mtDNA damage was determined by quantitative polymerase chain reaction. All veterans completed two consecutive maximal exercise tests separated by 24 hours. During each exercise bout, the time of ventilatory threshold (VT) was identified using the v‐slope method. The time of VT was identified as an effort‐independent measure of exercise performance reflective of mitochondrial capacity. MtDNA damage was correlated with physical activity (r=0.54, p= 0.004), time of VT at second b out exercise (r=−0.65, p= 0.001), but was not correlated with pack years, fatigue severity or time of VT at first bout exercise. Using partial correlation by controlling for physical activity and pack years, mtDNA damage was correlated to time of VT at second bout exercise (r=−0.64, p= 0.004). This is the first study to describe mitochondrial dysfunction through the relationship between mtDNA damage and an earlier onset of VT in veterans with unexplained fatigue. This may indicate that post‐exertion fatigue may be related to mitochondrial dysfunction. This work may guide new diagnostic testing and treatments for veterans suffering from with unexplained fatigue.Support or Funding InformationVA Grants 1I21RX001079‐01 and 1I21CX000797‐01 (Michael J Falvo).