Aug 2026· Journal of Cachexia, Sarcopenia and Muscle· Vol 17· 0 citations· 39 references
Medicine
TL;DR
Sustaining daily ultrarunning for more than 1 year induces substantial skeletal muscle remodelling, including reduced muscle size, impaired contractile function and mitochondrial maladaptations, despite largely preserved endocrine and haematological stability.
Abstract
ABSTRACT Background Ultra‐endurance sports are increasingly popular, yet the long‐term physiological consequences of sustained extreme training loads remain poorly understood. In particular, the effects of prolonged ultra‐endurance exercise on skeletal muscle structure, function and molecular remodelling are largely unknown. This case study examined a highly experienced ultra‐endurance athlete who completed a world‐record attempt to run 30 300 km, with extensive phenotyping focusing on skeletal muscle adaptations and recovery. Methods A 49‐year‐old male athlete (172 cm, 65 kg) ran ~70 km daily for 15 months. Musculoskeletal, cardiac and visceral ultrasonography, leg muscle strength and power measurements were performed before and after the challenge. Muscle biopsies (n = 4) from vastus lateralis were obtained immediately after completion and during 17 months of recovery to assess myosin heavy chain (MHC) composition, mitochondrial electron transport chain (ETC) complexes and proteins involved in mitochondrial turnover, autophagy and inflammation. Body composition, haematological and biochemical markers, and gut microbiota composition were monitored longitudinally. Results The athlete ran 30 300 km over 444 days, maintaining a daily distance of ~70 km despite substantial musculoskeletal discomfort, including a tibial stress reaction mid‐challenge, which resolved gradually with continued running. Body mass decreased by ~3 kg, primarily reflecting fat loss (~83%), accompanied by reductions in muscle thickness, maximal strength and power. Circulating creatine kinase (3–15‐fold), oxidative stress markers (~50%) and GDF8 (~10%–50%) were sustainedly increased, whereas IGF‐I decreased (~10%–40%), suggesting a reduced anabolic environment during the challenge. Muscle biopsy analyses revealed a progressive recovery of mitochondrial function during the 17 months following the challenge, as evidenced by a progressive increase in ETC protein abundance and the expression of regulators of mitochondrial dynamics and quality control (MFN2, PARKIN, DRP1). In contrast, markers of autophagy, apoptosis and inflammation were decreased during the 17‐months post‐challenge (LC3A/B‐I by ~50%, CASP3 by ~60% and NF‐κBSer536 by ~20%). Muscle fibre composition showed extreme predominance of slow fibres (nearly 100% MHC‐I), which persisted during recovery. Most molecular and functional alterations gradually resolved within 10–17 months. Gut microbiota diversity increased during the challenge, with enrichment of Bifidobacterium during running and Akkermansia during recovery. Conclusions Sustaining daily ultrarunning for more than 1 year induces substantial skeletal muscle remodelling, including reduced muscle size, impaired contractile function and mitochondrial maladaptations, despite largely preserved endocrine and haematological stability. These findings highlight skeletal muscle as a primary physiological system challenged during extreme endurance exercise and demonstrate that recovery from such perturbations may require more than one year.
ABSTRACT It remains unclear why exercising damaged muscles is perceived as disproportionately more effortful. Given the known role of inorganic phosphate (Pi) in fatigue and afferent sensory signaling, we tested whether muscle damage disrupts phosphate metabolism and whether this is associated with heightened ratings of perceived exertion (RPE). Eighteen adults (23 ± 4 years) completed assessments before and 48 h after muscle damage induced by unilateral eccentric knee extensions (EIMD); the contralateral leg served as control. Magnetic resonance imaging quantified quadriceps cross‐sectional area (Qcsa) and 31P‐MR spectroscopy quantified Pi, phosphocreatine (PCr), Pi/PCr, ATPγ and pH at rest, during knee‐extension exercise, and recovery. RPE was recorded throughout exercise. At 48 h, the EIMD leg showed increased soreness (17‐fold), reduced maximum voluntary contraction (−18.4% ± 3.8%) and increased Qcsa (+2.8% ± 0.4%; mean individual percentage changes ± SEM; p < 0.001). Visit × condition interactions were observed for Pi, Pi/PCr, and ATPγ at rest (ηp2 = 0.31–0.35) and across rest, exercise and recovery (ηp2 = 0.66–0.78), but not for PCr or pH. This reflected sustained elevations of Pi and Pi/PCr, and lower ATPγ in the EIMD leg alongside higher RPE at 48 h. Elevated resting Pi/PCr was strongly associated with elevated RPE (r = 0.856, p < 0.001), whereas exercise‐induced Pi/PCr changes were not associated with RPE. Overall, EIMD causes a sustained disturbance in muscle phosphate homeostasis that is strongly associated with elevated RPE. These findings provide new evidence linking resting muscle phosphate‐metabolic disturbance with heightened effort perception after damage.
Jamie S McPhee, Aneurin J Kennerley, Jean‐Christophe Lagacé et al.· Scandinavian Journal of Medi...· 0 citations
Reductions in musculoskeletal mass and function can occur with ageing and disuse. While resistance exercise training is known to minimise these detriments, it is not always feasible. Vortex wave stimulation (VWS) may mitigate skeletal muscle decline in such scenarios. The aim of the present study was to explore the acute physiological and metabolic effects of VWS in healthy older adults. Fourteen participants consumed deuterium oxide (D2O) stable oral isotope tracer for 7 days. Serial skeletal muscle biopsies were obtained to measure integrated rates of myofibrillar (iMyoPS) and sarcoplasmic (iSarcPS) muscle protein synthesis and regulatory signalling over ∼48 h before (habitual) and after two consecutive-day bouts of VWS. Myoelectrical activity and muscle oxygenation during VWS, and pre-post changes in peripheral blood flow and concentrations of inflammatory and bone turnover markers were also measured. There was an increase in iMyoPS (0.23% day-1, P = 0.025), but not iSarcPS (0.07% day-1, P = 0.582) above habitual rates following VWS. There was no difference in the expression of anabolic signalling proteins, nor peripheral blood flow following VWS. Myoelectrical activity increased during VWS (9.47 µV, P = 0.010), while muscle oxygenation decreased at the gastrocnemius (P = 0.001) and quadriceps (P = 0.017). There was a reduction in P1NP (8.27 µg L-1) and lactate (0.84 mmol L-1) concentration post-VWS (both P < 0.001), while there was no difference in other biomarkers. This is the first study to demonstrate that VWS elicits acute physiological responses congruent with musculoskeletal adaptive remodelling, which warrants further exploration. KEY POINTS: Resistance exercise is known to mitigate skeletal muscle atrophy associated with ageing and/or disuse but is not always feasible. We investigated, for the first time, the effects of a novel mechanical stimulus - vortex wave stimulation (VWS) - on integrated rates of myofibrillar and sarcoplasmic muscle protein synthesis, alongside other musculoskeletal and physiological outcomes, in healthy older adults. We demonstrated that VWS elevated myofibrillar, but not sarcoplasmic muscle protein synthesis compared to baseline, while increasing myoelectrical activity and reducing muscle oxygen saturation, lactate and bone turnover markers. These findings suggest VWS elicits acute physiological responses congruent with musculoskeletal adaptive remodelling.
A. Waddell, Marie Korzepa, Archie E. Belfield et al.· Journal of Physiology· 0 citations
INTRODUCTION
This study examined the effects of various cycling endurance training modalities, matched for total workload, on muscle mechanical and architectural characteristics in older adults.
METHODS
Fifty healthy participants (25 females, 59-79 yrs) were randomly assigned to five age and sex matched groups: one control and four workload-matched training groups (moderate-intensity continuous, heavy-intensity continuous, high-intensity interval, and heavy-intensity continuous in eccentric cycling). Training consisted of three weekly sessions over 8 weeks, with evaluations conducted at the beginning and end of the intervention with maximal voluntary isometric contractions at five different knee angles (90, 75, 60, 45, 30°) and maximal concentric and eccentric isokinetic contractions at five different knee angular velocities (45, 90, 150, 210, 250°/s). Maximum voluntary isometric torque (Tmax) and optimal knee angle (KAopt) were obtained from the isometric contractions; eccentric torque (Tecc) and maximum concentric knee angular velocity (Vmax) were obtained from the isokinetic contractions. The muscle architecture of vastus lateralis (VL) at rest (muscle thickness, pennation angle, and fascicle length) was investigated as well.
RESULTS
No statistical differences were detected between groups or time points in VL architecture, in KAopt and in Vmax. A main effect of time was observed for Tmax (p < 0.001, η2p = 0.458) and Tecc (p = 0.002, η2p = 0.191) in all the investigated training groups. The within-group comparisons indicate significant increases in Tmax in the training groups, but not in the control group.
CONCLUSIONS
Commonly applied endurance exercises improve muscle mechanical capacity (Tmax and Tecc) in older adults, with no structural (architectural) muscle remodelling, when matched for workload.
M. Trinchi, Samuel D’Emanuele, A. Monte et al.· Experimental Gerontology· 0 citations
ABSTRACT This study investigated neuromuscular fatigue and perceived fatigability across different high‐intensity endurance running protocols. Twelve males (mean ± SD; V˙O2max: 52.2 ± 6.9 mL/kg/min) ran ∼8.0 km: (i) at the velocity associated to the respiratory compensation point (vRCP; 5 × 8 min bouts ‒ RUN100%RCP); (ii) at 30% above vRCP (10 × 3 min bouts ‒ RUN130%RCP); and (iii) at 50% above vRCP (20 × 80 s bouts ‒ RUN150%RCP). Before and for 6 h post‐exercise, voluntary and evoked contractions of knee‐extensors were assessed, alongside tiredness, leg pain, and perceived recovery. Following all protocols, voluntary activation remained depressed for up to 4 h post‐exercise, while voluntary peak force was reduced for at least 6 h (p < 0.05). Other neuromuscular function markers reduced (p < 0.05) according to the protocol. No time × protocol interaction was observed for any neuromuscular function marker (p > 0.05). Aggregate data (protocol effect, p < 0.05) evidenced greater reduction in neural drive to vastus lateralis (RMSVL/Mwamp) after RUN100%RCP (−20%) compared to RUN130%RCP (−3%) and RUN150%RCP (−7%); and greater reduction in late rate of force development (RFD; 100–200 ms) and contractile function (Qtwpot) after RUN150%RCP (−18% and −8%, respectively) than RUN100%RCP (−8% and −2%, respectively). Leg pain and tiredness remained elevated (p < 0.05) for at least 6 h following all protocols. Leg pain and tiredness were greater for up to 4 h and for at least 6 h, respectively, after RUN150%RCP than RUN100%RCP (time × protocol interaction; p < 0.05). The choice of exercise protocol influences the extent of reduction in vastus lateralis neural drive, impairments in knee‐extensors contractile function, and perceived fatigability for hours following a high‐intensity endurance running.
Y. M. Dutra, Paloma Tavares Mendonça, Stuart Goodall et al.· European Journal of Sport Sc...· 1 citation
BACKGROUND
Aging is associated with progressive declines in skeletal muscle mass (SMM) and substantial interindividual variability in adaptations to resistance training (RT). However, whether training load intensity influences hypertrophic responsiveness in older adults remains unclear.
OBJECTIVE
To investigate the effects of two commonly prescribed RT loading schemes (15RM and 10RM) on estimated SMM adaptations and responsiveness in older women.
METHODS
Twenty-seven older women (67.7 ± 4.9 years; 65.7 ± 10.6 kg; 154.5 ± 5.8 cm) completed two 8-week RT interventions performed at 15RM and 10RM in a randomized crossover design, separated by a 12-week detraining period. Estimated SMM was assessed using dual-energy X-ray absorptiometry. Responsiveness was operationally defined using the standard error of measurement, and participants were classified as responders (RP) or non-responders (N-RP) according to changes in estimated SMM.
RESULTS
Both loading schemes promoted significant and comparable increases in estimated SMM (15RM: +0.62 ± 0.4 kg vs. 10RM: +0.43 ± 0.3 kg). Overall, 61.1% of participants were classified as responders in at least one condition, whereas 38.9% were classified as non-responders. Responsiveness status was consistent across conditions for most participants, with 48.1% classified as responders under both loading schemes and 25.9% as non-responders under both conditions. Only seven participants (25.9%) changed responsiveness status between interventions. No clear pattern indicated a greater likelihood of responsiveness with either loading scheme.
CONCLUSIONS
Results suggest that both the 10RM and 15RM RT protocols significantly increase estimated SMM in older women, with no significant differences between training conditions. Although substantial interindividual variability in adaptive responses exists, training load intensity does not appear to meaningfully influence responsiveness status in most individuals. These findings suggest that both loading schemes can be effectively prescribed to promote SMM gains in older women.
A. Ribeiro, Gerardo Sansone, P. Cunha et al.· Experimental Gerontology· 0 citations
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