Telomere shortiening (Elizabeth Unger)

Seanko

Well-Known Member
Dr Elizabeth Unger & colleagues at the CDC in Atlanta have published a paper on Telomere shortening in ME/CFS in the FASEB biology journal
Telomere Length Analysis in Chronic Fatigue Syndrome
Below is a readable summary from ME Research UK
Telomere Shortening




Telomeres are ‘caps’ of DNA and protein located at the end of chromosomes to protect them from deteriorating or becoming fused with other chromosomes when cells are dividing. Structurally, they consist of a region of hundreds or even thousands of repetitive sequences of nucleotide letters, usually repeats of the sequence TTAGGG.

One of the characteristics of telomeres is that they become shorter during the ageing process; they shorten every time a cell divides – human blood cells shorten by 30−70 base pairs per year on average. This weakens the structural integrity of cells and causes them to age and die faster. It remains unknown whether telomere shortening is simply a sign of ‘cellular age’ or whether it contributes to the ageing process more directly. We do know, however, that telomeres are shorter than usual in patients with diseases like cancer, osteoporosis and the cardiovascular disorders, even when the effect of ageing is taken into account.

Recently, evidence has come to light that telomeres are also shorter than normal in people with ME/CFS. The study, presented as an abstract at the Experimental Biology 2016 Meeting and published this month in The FASEB Journal (read more), comes from Prof Unger’s group at the CDC in Atlanta. The researchers isolated DNA from whole blood samples from 639 participants who had taken part in the 2004 Georgia CFS Surveillance study (read more), one of the two population-based longitudinal studies of CFS undertaken by the CDC in the past 20 years. From each sample, relative telomere length was measured using real-time PCR. Using questionnaire-based methods, 64 participants were classified as fulfilling all the criteria for Fukuda 1994 CFS; 77 fulfilled all the criteria but had other exclusionary conditions; 302 fulfilled only some of the criteria (‘fatigue’ group in this case), and 196 met none of the criteria (‘healthy controls’ in this case).

Overall, telomere lengths were found to be significantly longer in the healthy controls than in the Fukuda 1994 CFS patients or in the group of ‘fatigue’ patients, and these differences remained significant after statistical adjustment for differences between groups. Based on adjusted group means, telomere length was shorter by 593 and 508 base pairs in the CFS and ‘fatigue’ groups, respectively, compared with the controls. As expected, there was a correlation between telomere length and age in the total sample. Given this evidence, the authors suggest that CFS should be considered a condition of ‘telomere shortening’.

As shortened telomeres are also found in a range of other chronic diseases, including cancer (read more), diabetes, Alzheimer’s disease and Parkinson’s disease, the phenomenon is most likely associated with chronic illness per se, rather than with ME/CFS in particular. It is intriguing to note, however, that telomeres are highly susceptible to oxidative stress, which is known to damage DNA; the higher the cellular oxidative stress levels the greater the degree of shortening (read more). Given that ME Research UK-funded work has found high levels of oxidative stress and associated arterial stiffness to be a feature in ME/CFS patients (read more), it may be that telomere shortening is intimately linked with ongoing inflammatory processes.

Though telomere length decreases with age, it seems that the process is not inevitable and that they can also increase in length. At present, scientists are exploring interventions to lengthen telomeres. Telomerase is the enzyme that repairs shortened or dysfunctional telomeres, and various telomerase-activating drugs are under development, with some success as recent work on blood disorders has shown (read more). Also, statins seem to have a protective role against telomere shortening, and lifestyle factors may have an important role to play. For example, telomere length is positively linked with nutritional status in human and animal studies (see a review), possibly through the effects of various nutrients on reducing inflammation and oxidative stress, and a study in 2013found that lifestyle changes (a plant-based diet, moderate exercise, stress reduction and weekly group support) increased telomere length by about 10% in men with prostate cancer.

Of course, it is too early to know the precise meaning of telomere shortening in ME/CFS patients and what, if anything, should be done to combat it, but these intriguing findings add to the evidence of an underlying disease process in people with the illness, and we await the publication of the full scientific paper with great interest.
 

Seanko

Well-Known Member
The full abstract details from the FASEB journal are below.
Telomere Length Analysis in Chronic Fatigue Syndrome
Telomere Length Analysis in Chronic Fatigue Syndrome

  1. E R Unger, J Murray, LP Oakley JM Lin and MS Rajeevan
    Centers for Disease Control and Prevention, Atlanta, GA
Abstract

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.
Footnotes

  • This abstract is from the Experimental Biology 2016 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
 
Last edited:

Cort

Founder of Health Rising and Phoenix Rising
Staff member
The details from the FASEB journal are below.
Telomere Length Analysis in Chronic Fatigue Syndrome

  1. E R Unger, J Murray, LP Oakley JM Lin and MS Rajeevan
  1. mce-anchor
    Centers for Disease Control and Prevention, Atlanta, GA
Abstract

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.
Footnotes

  • This abstract is from the Experimental Biology 2016 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nice!

Hey, this is another finding using the Reeves criteria - as poor as it is - that fits with what we would expect to find. Interesting that low telomere length was was found in the non ME/CFS but still fatigue group as well. A nice large study as well - people - no one is going to dispute these results

Nice as well MERUK highlighted increased oxidative stress. Increased oxidative stress is one of the most consistent results in ME/CFS. Shungu's lactate findings suggest it is increased in the brain as well as the body.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
These preliminary data imply that chronic pain is a more serious condition than has typically been recognized in terms of bodily aging.

Shortened telomere length was associated with increased pain in FM as well

J Pain. 2012 Oct;13(10):959-69. doi: 10.1016/j.jpain.2012.07.003.Pain is associated with short leukocyte telomere length in women with fibromyalgia. Hassett AL1, Epel E, Clauw DJ, Harris RE, Harte SE, Kairys A, Buyske S, Williams DA.

Telomere length, considered a measure of biological aging, is linked to morbidity and mortality. Psychosocial factors associated with shortened telomeres are also common in chronic pain; yet, little is known about telomere length in pain populations. Leukocyte telomere length was evaluated in 66 women with fibromyalgia and 22 healthy female controls. Participants completed questionnaires and a subgroup of fibromyalgia patients underwent quantitative sensory testing (QST; n = 12) and neuroimaging (n = 12). Telomere length was measured using the quantitative polymerase chain reaction method.

Although patients had shorter telomere length than controls, the difference was not statistically significant. However, higher levels of pain within fibromyalgia were associated with shorter telomere length (P = .039).

When pain and depression were combined, patients categorized as high-pain/high-depression had an age-adjusted telomere length 265 base pairs shorter than those with low-pain/low-depression (P = .043), a difference consistent with approximately 6 years of chronological aging.

In the subset tested, telomere length was also related to pain threshold and pain sensitivity, as well as gray matter volume, such that patients with shorter telomeres were more sensitive to evoked pain and had less gray matter in brain regions associated with pain processing (eg, primary somatosensory cortex). These preliminary data support a relationship between pain and telomere length.
PERSPECTIVE:

Our findings support a link between premature cellular aging and chronic pain. These preliminary data imply that chronic pain is a more serious condition than has typically been recognized in terms of bodily aging.

Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserve
 

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