Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy

Background: Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-based exercise training program on fitness, muscle, and motor function in FSHD patients. Methods: Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n = 8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35 minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO 2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention. Results: The compliance rate was 91% in TG. Significant improvements with training were observed in the VO 2 peak (+19%, P = 0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P = 0.008) and 46% (P = 0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG. Conclusions: A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue

Short Telomere Length Is Related to Limitations in Physical Function in Elderly European Adults

The present study aims to explore the potential influence of leucocyte telomere length (LTL) on both a single indicator and a composite construct of physical functioning in a large European population of elderly men and women across diverse geographical locations. A total of 1,221 adults (65–79 years) were recruited from five European countries within the framework of NU-AGE study. The physical functioning construct was based on the 36-item Short Form Health Survey. Handgrip strength was used as a single indicator of muscle function and LTL was assessed using quantitative real-time PCR. Women had significantly longer (p < 0.05) LTL than men. Participants in Poland had significantly shorter LTL than in the other study centers, whereas participants in the Netherlands had significantly longer LTL than most of the other centers (p < 0.01). An analysis of LTL as a continuous outcome against physical functioning by using linear models revealed inconsistent findings. In contrast, based on an analysis of contrasting telomere lengths (first vs. fifth quintile of LTL), a significant odds ratio (OR) of 1.7 (95% CI: 1.1 – 2.6; p < 0.05) of having functional limitation was observed in those belonging to the first LTL quintile compared to the fifth. Interestingly, having the shortest LTL was still related to a higher likelihood of having physical limitation when compared to all remaining quintiles (OR: 1.5, 95% CI: 1.1 – 2.1; p < 0.05), even after adjustment by study center, age, sex, and overweight status. Collectively, our findings suggest that short LTL is an independent risk factor that accounts for functional decline in elderly European populations. The influence of LTL on functional limitation seems driven by the detrimental effect of having short telomeres rather than reflecting a linear dose-response relationship

Skeletal muscle telomere length is not impaired in healthy physically active old women and men

We have previously shown that the number of satellite cells is lower in old than young men and women. The aim of this study was to further explore the effects of aging on the regenerative potential of skeletal muscle in 16 young and 26 old men and women with comparable physical activity level (young, 25 +/- 4 years; old, 75 +/- 4 years). Mean and minimum telomere lengths were determined using Southern blot analyses on biopsies obtained from the tibialis anterior muscle. There were no significant age or gender effects on mean and minimal telomeric lengths, suggesting that the replicative potential in the remaining satellite cells in the tibialis anterior muscle is not impaired with increasing age and the existence of in vivo regulatory mechanisms allowing the maintenance of telomere length. These results imply that moderate physical activity regularly performed by old subjects is not associated with accelerated telomere loss

Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r = 0.69, p = .020) and in mean (r = 0.74, p = .014) and minimum SMTL (r = 0.88, p = .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r 2 = 0.30, p = .030), percentage total body (r 2 = 0.43, p = .014), and thigh (r 2 = 0.55, p = .004) fat, while minimum SMTL was associated with fat-free mass (r 2 = 0.27, p = .020) and thigh muscle area (r 2 = 0.42, p = .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.peerReviewe

Exercise training in normobaric hypoxia in endurance runners. III. Muscular adjustments of selected gene transcripts.

We hypothesized that specific muscular transcript level adaptations participate in the improvement of endurance performances following intermittent hypoxia training in endurance-trained subjects. Fifteen male high-level, long-distance runners integrated a modified living low-training high program comprising two weekly controlled training sessions performed at the second ventilatory threshold for 6 wk into their normal training schedule. The athletes were randomly assigned to either a normoxic (Nor) (inspired O2 fraction = 20.9%, n = 6) or a hypoxic group exercising under normobaric hypoxia (Hyp) (inspired O2 fraction = 14.5%, n = 9). Oxygen uptake and speed at second ventilatory threshold, maximal oxygen uptake (VO2 max), and time to exhaustion (Tlim) at constant load at VO2 max velocity in normoxia and muscular levels of selected mRNAs in biopsies were determined before and after training. VO2 max (+5%) and Tlim (+35%) increased specifically in the Hyp group. At the molecular level, mRNA concentrations of the hypoxia-inducible factor 1alpha (+104%), glucose transporter-4 (+32%), phosphofructokinase (+32%), peroxisome proliferator-activated receptor gamma coactivator 1alpha (+60%), citrate synthase (+28%), cytochrome oxidase 1 (+74%) and 4 (+36%), carbonic anhydrase-3 (+74%), and manganese superoxide dismutase (+44%) were significantly augmented in muscle after exercise training in Hyp only. Significant correlations were noted between muscular mRNA levels of monocarboxylate transporter-1, carbonic anhydrase-3, glucose transporter-4, and Tlim only in the group of athletes who trained in hypoxia (P < 0.05). Accordingly, the addition of short hypoxic stress to the regular endurance training protocol induces transcriptional adaptations in skeletal muscle of athletic subjects. Expressional adaptations involving redox regulation and glucose uptake are being recognized as a potential molecular pathway, resulting in improved endurance performance in hypoxia-trained subjects

Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication

With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation–induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1(+) satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7(+) cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.—Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication