Telomere Length Analysis in Chronic Fatigue Syndrome
Authors: Unger E R , Murray J , Oakley LP , Lin JM , Rajeevan MS 
Published: November 2023

Background

Chronic fatigue syndrome (CFS) is a severely disabling condition associated with multi‐system symptoms including marked post‐exertional malaise, fatigue, pain, unrefreshing sleep and cognitive impairment. The symptoms and risk factors share features with accelerating aging. Aging and a variety of metabolic, inflammatory, infectious and neoplastic conditions have been associated with accelerated telomere attrition. This analysis was performed to evaluate whether CFS shares this association.

Methods

DNA was isolated from 705 PAXgene whole blood samples from 751 participants in the 2007–09 follow‐up of the Georgia CFS Surveillance study who completed the clinical evaluation used to identify exclusionary medical and psychiatric conditions that could explain fatigue. Using the 1994 CFS Research Case Definition with questionnaire‐based subscale thresholds for fatigue, function and symptoms, participants were classified as: 1) CFS if all criteria met (n=71); 2) CFS‐X if CFS with exclusionary conditions (n=78); 3) Insufficient Symptoms/Fatigue (ISF) if only some criteria met, regardless of exclusionary conditions (n=340); 4) Non‐Fatigued (NF) if no criteria met and no exclusionary conditions (n=212;47 NF participants with exclusions were not included and 3 could not be classified). Relative telomere length was measured using real‐time PCR. Telomere specific primers generate a signal proportional to total sum of the length of all telomeres in the sample (T). Telomere signal is normalized to signal from primers to single‐copy gene (S). The T/S ratio is proportional to average telomere length per cell. T/S is expressed relative to reference DNA, assigned T/S of 1.0. Conversion of T/S to Southern blot hybridization determination of terminal restriction fragment telomere length in base pairs (bp) was based on data from 20 healthy volunteers tested by both methods. Linear and logistic models were used to examine association between CFS, T/S ratio and covariates. Level of significance was set at p < 0.05. This analysis concerned 639 participants with telomere, classification and co‐variate data: 77 CFS‐X, 64 CFS, 302 ISF, and 196 NF.

Results

Age (48.04 ± 0.38 years) did not differ across groups, but obesity, sex, race, education and income, significantly differed. T/S ratios ranged from 0.269 to 4.138. When comparing T/S ratios across groups, telomere lengths were significantly shorter in CFS and ISF than NF (CFS: 0.93±0.03, ISF: 0.94±0.02; NF: 1.09±0.04). These differences remained significant after adjusting for covariates (age, BMI, waist‐hip‐ratio, education, and sex). Based on adjusted group means, telomere length was shorter by 212, 593 and 508 bp in CFS‐X, CFS and ISF compared to NF. As expected there was a significant negative correlation between telomere length and age in the study sample overall. NF subjects started with long telomeres but shortened at a faster rate (59 bp/year) than the rate of telomere shortening in CFS‐X (25.4 bp/year), CFS (21.2 bp/year) and ISF (4.2 bp/year).

Conclusions

Our results indicate that CFS should be included in the list of conditions associated with telomere shortening. Further work is needed to evaluate if the shortening has functional significance in CFS.