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Medicine & Science in Sports & Exercise:
BASIC SCIENCES: Original Investigations

Athletes with Exercise-Associated Fatigue Have Abnormally Short Muscle DNA Telomeres

COLLINS, MALCOLM1; RENAULT, VALÉRIE2; GROBLER, LIESL A.1; ST CLAIR GIBSON, ALAN1; LAMBERT, MICHAEL I.1; WAYNE DERMAN, E.1; BUTLER-BROWNE, GILLIAN S.2; NOAKES, TIMOTHY D.1; MOULY, VINCENT2

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Abstract

COLLINS, M., V. RENAULT, L. A. GROBLER, A. ST CLAIR GIBSON, M. I. LAMBERT, E. W. DERMAN, G. S. BUTLER-BROWNE, T. D. NOAKES, and V. MOULY. Athletes with Exercise-Associated Fatigue Have Abnormally Short Muscle DNA Telomeres. Med. Sci. Sports Exerc., Vol. 35, No. 9, pp. 1524–1528, 2003.

Introduction/Purpose : Although the beneficial health effects of regular moderate exercise are well established, there is substantial evidence that the heavy training and racing carried out by endurance athletes can cause skeletal muscle damage. This damage is repaired by satellite cells that can undergo a finite number of cell divisions. In this study, we have compared a marker of skeletal muscle regeneration of athletes with exercise-associated chronic fatigue, a condition labeled the “fatigued athlete myopathic syndrome” (FAMS), with healthy asymptomatic age- and mileage-matched control endurance athletes.

Methods: Muscle biopsies of the vastus lateralis were obtained from 13 patients diagnosed with FAMS and from 13 healthy control subjects. DNA was extracted from the muscle samples and their telomeric restriction fragment (TRF) or telomere lengths were measured by Southern blot analysis.

Results: All 13 symptomatic athletes reported a progressive decline in athletic performance, decreased ability to tolerate high mileage training, and excessive muscular fatigue during exercise. The minimum value of TRF lengths (4.0 ± 1.8 kb) measured on the DNA from vastus lateralis biopsies from these athletes were significantly shorter than those from 13 age- and mileage-matched control athletes (5.4 ± 0.6 kb, P < 0.05). Three of the FAMS patients had extremely short telomeres (1.0 ± 0.3 kb). The minimum TRF lengths of the remaining 10 symptomatic athletes (4.9 ± 0.5 kb, P < 0.05) were also significantly shorter that those of the control athletes.

Conclusion : These findings suggest that skeletal muscle from symptomatic athletes with FAMS show extensive regeneration which most probably results from more frequent bouts of satellite cell proliferation in response to recurrent training- and racing-induced muscle injury.

Prolonged, demanding, weight-bearing exercise has been reported to cause both acute and more chronic muscle damage (reviewed in 12). Although adult skeletal muscles are made up of highly differentiated, elongated multinucleated postmitotic cells, they also contain a small population of quiescent mononucleated satellite cells that are located between the sarcolemma and the basement membrane (13). These cells are responsible for both muscle growth and repair. After skeletal muscle damage, the satellite cells proliferate and then fuse to repair or replace the damaged fibers. Some of these mononucleated cells will return to quiescence to restore the population of satellite cells (3). With age, there is a progressive reduction in both the proliferative capacity and the total number of satellite cells (15,16). The proliferative capacity of the satellite cells is limited, in part, by the loss of telomeric sequences, which are specialized DNA-protein structures at the end of the chromosomes (1). During each somatic cell division, a small piece of telomeric DNA is lost. Once the telomeric DNA becomes too short a DNA damage signal is initiated causing the cell to become senescent and stop dividing, thus limiting the regenerative capacity of the cell (6). Since the proliferating satellite cells will lose a small piece of telomeric DNA during each replicative cycle, the newly incorporated DNA in the repaired fiber will have shorter telomeres (5). Thus, the number of cycles of satellite cell proliferation as well as their remaining regenerative capacity can be determined indirectly by measuring the telomeric length or, more specifically, the minimum telomeric restriction fragment (TRF) lengths of DNA from skeletal muscle biopsies (5,16).

Athletes suffering from exercise-related chronic fatigue are ideally suited for studying any potential long-term detrimental effects of high-volume endurance training. These athletes have a long history of very high training loads and participation in competitions. They demonstrated a precipitous decline in performance which is not related to ordinary aging, they present with complaints of chronic fatigue dominated by skeletal muscle symptoms including excessive delayed-onset-muscle-soreness, muscle stiffness, weakness, and tenderness as well as a failure to adapt to training. Typically they have sought the help of many clinicians without success. Clinical characteristics and recognized skeletal muscle pathological features, including those of the muscular dystrophies and mitochondrial myopathies, are also excluded in these athletes. The athletes who fulfill these criteria have previously been described as suffering from the “fatigued athlete myopathic syndrome” (FAMS) (7,20,21).

In this study, we have compared the lengths of the TRF in DNA isolated from biopsies of vastus lateralis muscles sampled from endurance athletes suffering from FAMS with those from control athletes, matched for age and historical training volume. We postulate that the skeletal muscle symptoms of the athletes suffering from FAMS might be caused by extensive muscle regeneration.

©2003The American College of Sports Medicine

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