Association of chronic fatigue syndrome with premature telomere attrition

Abstract

Background: Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a severely debilitating condition of unknown etiology. The symptoms and risk factors of ME/CFS share features of accelerated aging implicated in several diseases. Using telomere length as a marker, this study was performed to test the hypothesis that ME/CFS is associated with accelerated aging. Methods: Participant (n=639) data came from the follow-up time point of the Georgia CFS surveillance study. Using the 1994 CFS Research Case Definition with questionnaire-based subscale thresholds for fatigue, function, and symptoms, participants were classified into four illness groups: CFS if all criteria were met (n=64), CFS-X if CFS with exclusionary conditions (n=77), ISF (insufficient symptoms/fatigue) if only some criteria were met regardless of exclusionary conditions (n=302), and NF (non-fatigued) if no criteria and no exclusionary conditions (n=196). Relative telomere length (T/S ratio) was measured using DNA from whole blood and real-time PCR. General linear models were used to estimate the association of illness groups or T/S ratio with demographics, biological measures and covariates with significance set at p<0.05. Results: The mean T/S ratio differed significantly by illness group (p=0.0017); the T/S ratios in CFS (0.90±0.03) and ISF (0.94±0.02) were each significantly lower than in NF (1.06±0.04). Differences in T/S ratio by illness groups remained significant after adjustment for covariates of age, sex, body mass index, waist-hip ratio, post-exertional malaise and education attainment. Telomere length was shorter by 635, 254 and 424 base pairs in CFS, CFS-X and ISF, respectively, compared to NF. This shorter telomere length translates to roughly 10.1-20.5, 4.0-8.2 and 6.6-13.7years of additional aging in CFS, CFS-X and ISF compared to NF respectively. Further, stratified analyses based on age and sex demonstrated that the association of ME/CFS with short telomeres is largely moderated by female subjects<45years old. Conclusions: This study found a significant association of ME/CFS with premature telomere attrition that is largely moderated by female subjects<45years old. Our results indicate that ME/CFS could be included in the list of conditions associated with accelerated aging. Further work is needed to evaluate the functional significance of accelerated aging in ME/CFS.