Tommy Aune Rehn

Telomere Length and Long-Term Endurance Exercise: Does Exercise Training Affect Biological Age? A Pilot Study

Background Telomeres are potential markers of mitotic cellular age and are associated with physical ageing process. Long-term endurance training and higher aerobic exercise capacity (VO2max) are associated with improved survival, and dynamic effects of exercise are evident with ageing. However, the association of telomere length with exercise training and VO2max has so far been inconsistent. Our aim was to assess whether muscle telomere length is associated with endurance exercise training and VO2max in younger and older people. Methods Twenty men; 10 young (22–27 years) and 10 old (66–77 years), were studied in this cross-sectional study. Five out of 10 young adults and 5 out of 10 older were endurance athletes, while other halves were exercising at a medium level of activity. Mean telomere length was measured as telomere/single copy gene-ratio (T/S-ratio) using quantitative real time polymerase chain reaction. VO2max was measured directly running on a treadmill. Results Older endurance trained athletes had longer telomere length compared with older people with medium activity levels (T/S ratio 1.12±0.1 vs. 0.92±0.2, p = 0.04). Telomere length of young endurance trained athletes was not different than young non-athletes (1.47±0.2 vs. 1.33±0.1, p = 0.12). Overall, there was a positive association between T/S ratio and VO2max (r = 0.70, p = 0.001). Among endurance trained athletes, we found a strong correlation between VO2max and T/S ratio (r = 0.78, p = 0.02). However, corresponding association among non-athlete participants was relatively weak (r = 0.58, p = 0.09). Conclusion Our data suggest that VO2max is positively associated with telomere length, and we found that long-term endurance exercise training may provide a protective effect on muscle telomere length in older people.

Intrinsic skeletal muscle alterations in chronic heart failure patients: a disease-specific myopathy or a result of deconditioning?

Chronic heart failure (CHF) patients frequently experience impaired exercise tolerance due to skeletal muscle fatigue. Studies suggest that this in part is due to intrinsic alterations in skeletal muscle of CHF patients, often interpreted as a disease-specific myopathy. Knowledge about the mechanisms underlying these skeletal muscle alterations is of importance for the pathophysiological understanding of CHF, therapeutic approach and rehabilitation strategies. We here critically review the evidence for skeletal muscle alterations in CHF, the underlying mechanisms of such alterations and how skeletal muscle responds to training in this patient group. Skeletal muscle characteristics in CHF patients are very similar to what is reported in response to chronic obstructive pulmonary disease (COPD), detraining and deconditioning. Furthermore, skeletal muscle alterations observed in CHF patients are reversible by training, and skeletal muscle of CHF patients seems to be at least as trainable as that of matched controls. We argue that deconditioning is a major contributor to the skeletal muscle dysfunction in CHF patients and that further research is needed to determine whether, and to what extent, the intrinsic skeletal muscle alterations in CHF represent an integral part of the pathophysiology in this disease.

Increasing Physical Activity of High Intensity to Reduce the Prevalence of Chronic Diseases and Improve Public Health

High incidence and prevalence of chronic diseases, increasing obesity and inactivity as well as rising health expenditure represent a set of developments that cannot be considered sustainable, and will have dire long-term consequences given the increasing proportion of elderly people in our society. Based on a review of the experiences from previous large scale population-based prevention programs and the documented effects of increased physical activity and cardiorespiratory fitness on chronic diseases and its risk factors, we argue that increased physical activity, especially vigorous physical activity, is a major way to reduce the prevalence of chronic diseases and improve public health. We conclude that a coordinated population-based intervention program for improved health through increased physical activity in the entire population, with a special focus on high intensity exercise, urgently needs to be implemented nationally and internationally.

Training Effects on Skeletal Muscle Calcium Handling in Human Chronic Heart Failure

PURPOSE Patients with chronic heart failure (CHF) typically complain about skeletal muscle fatigue. In rat experiments, reduced intracellular calcium release seems to be related to fatigue development in normal skeletal muscle but not in muscle from rats with CHF. We therefore hypothesize that training may not improve intracellular calcium cycling to the same extent in muscles from patients with CHF compared with healthy controls (HC). METHODS Thirteen HC and 11 CHF patients performed 6 wk of unilateral knee extensor endurance training. Computed tomographic examinations of the thigh and biopsies of vastus lateralis were obtained bilaterally before and after the training period. RESULTS Peak power of the trained leg was 10% and 14% greater than that in the untrained leg in HC and CHF, respectively. For the HC, training resulted in a higher Ca2+ release rate and a lower leak in the trained leg associated with a tendency of increased ryanodine receptor (RyR) content with reduced phosphorylation level. In the trained leg of CHF patients, RyR content was reduced without associated changes of either Ca2+ leak or release rate. CONCLUSIONS Training in HC has an effect on Ca2+ leak and release of the sarcoplasmic reticulum, but in CHF patients, training is achieved without such changes. Thus, calcium handling seems not to be the site of decreased exercise tolerance in CHF.

Temporary fatigue and altered extracellular matrix in skeletal muscle during progression of heart failure in rats

Patients with congestive heart failure (CHF) experience increased skeletal muscle fatigue. The mechanism underlying this phenomenon is unknown, but a deranged extracellular matrix (ECM) might be a contributing factor. Hence, we examined ECM components and regulators in a rat postinfarction model of CHF. At various time points during a 3.5 mo-period after induction of CHF in rats by left coronary artery ligation, blood, interstitial fluid (IF), and muscles were sampled. Isoflurane anesthesia was employed during all surgical procedures. IF was extracted by wicks inserted intermuscularly in a hind limb. We measured cytokines in plasma and IF, whereas matrix metalloproteinase (MMP) activity and collagen content, as well as the level of glycosaminoglycans and hyaluronan were determined in hind limb muscle. In vivo fatigue protocols of the soleus muscle were performed at 42 and 112 days after induction of heart failure. We found that the MMP activity and collagen content in the skeletal muscles increased significantly at 42 days after induction of CHF, and these changes were time related to increased skeletal muscle fatigability. These parameters returned to sham levels at 112 days. VEGF in IF was significantly lower in CHF compared with sham-operated rats at 3 and 10 days, but no difference was observed at 112 days. We conclude that temporary alterations in the ECM, possibly triggered by VEGF, are related to a transient development of skeletal muscle fatigue in CHF.

Exercise training increases protein O-GlcNAcylation in rat skeletal muscle

Protein O‐GlcNAcylation has emerged as an important intracellular signaling system with both physiological and pathophysiological functions, but the role of protein O‐GlcNAcylation in skeletal muscle remains elusive. In this study, we tested the hypothesis that protein O‐GlcNAcylation is a dynamic signaling system in skeletal muscle in exercise and disease. Immunoblotting showed different protein O‐GlcNAcylation pattern in the prototypical slow twitch soleus muscle compared to fast twitch EDL from rats, with greater O‐GlcNAcylation level in soleus associated with higher expression of the modulating enzymes O‐GlcNAc transferase (OGT), O‐GlcNAcase (OGA), and glutamine fructose‐6‐phosphate amidotransferase isoforms 1 and 2 (GFAT1, GFAT2). Six weeks of exercise training by treadmill running, but not an acute exercise bout, increased protein O‐GlcNAcylation in rat soleus and EDL. There was a striking increase in O‐GlcNAcylation of cytoplasmic proteins ~50 kDa in size that judged from mass spectrometry analysis could represent O‐GlcNAcylation of one or more key metabolic enzymes. This suggests that cytoplasmic O‐GlcNAc signaling is part of the training response. In contrast to exercise training, postinfarction heart failure (HF) in rats and humans did not affect skeletal muscle O‐GlcNAcylation level, indicating that aberrant O‐GlcNAcylation cannot explain the skeletal muscle dysfunction in HF. Human skeletal muscle displayed extensive protein O‐GlcNAcylation that by large mirrored the fiber‐type‐related O‐GlcNAcylation pattern in rats, suggesting O‐GlcNAcylation as an important signaling system also in human skeletal muscle.

Preserved metabolic reserve capacity in skeletal muscle of post-infarction heart failure patients.

It has been proposed that exercise capacity during whole body exercise in post‐infarction congestive heart failure (CHF) patients is limited by skeletal muscle function. We therefore investigated the balance between cardiopulmonary and muscular metabolic capacity. CHF patients (n=8) and healthy subjects (HS, n=12) were included. Patients with coronary artery disease (CAD, n=8) were included as a control for medication. All subjects performed a stepwise incremental load test during bicycling (∼24 kg muscle mass), two‐legged knee extensor (2‐KE) exercise (∼4 kg muscle mass) and one‐legged knee extensor (1‐KE) exercise (∼2 kg muscle mass). Peak power and peak pulmonary oxygen uptake (VO2peak) increased and muscle‐specific VO2peak decreased with an increasing muscle mass involved in the exercise. Peak power and VO2peak were lower for CHF patients than HS, with values for CAD patients falling between CHF patients and HS. During bicycling, all groups utilized 24–29% of the muscle‐specific VO2peak as measured during 1‐KE exercise, with no difference between the groups. Hence, the muscle metabolic reserve capacity during whole body exercise is not different between CHF patients and HS, indicating that appropriately medicated and stable post‐infarction CHF patients are not more limited by intrinsic skeletal muscle properties during whole body exercise than HS.

Normal training response in skeletal muscle of post-infarction heart failure patients

Abstract Congestive heart failure (CHF) patients experience reduced muscle fatigue resistance and exercise capacity. The aim of this study was to assess whether skeletal muscle in CHF patients has a normal training response compared to healthy subjects. We compared the effect of one-legged knee extensor (1-KE) endurance training in CHF patients (n=10), patients with coronary artery disease (CAD, n=9) and healthy subjects (n=13). The training response was evaluated by comparing trained leg and control leg after the training period. The fall in peak torque during 75 maximal 1-KE isokinetic contractions revealed that CHF patients were less fatigue resistant than healthy subjects in the control leg, but not in the trained leg. Peak power and peak oxygen uptake during dynamic 1-KE exercise was ~10–16% higher in trained leg than control leg. This training response was not significant different between groups. Muscle biopsies of vastus lateralis showed that fibre type composition was not different between trained leg and control leg. Capillary density was 6.5% higher in trained leg than control leg when all groups were pooled. In conclusion, the more fatigable skeletal muscle of CHF patients responds equally to endurance training compared to skeletal muscle of CAD patients and healthy subjects.