Abstract Skeletal muscle is a highly plastic tissue that rapidly adapts to changes in mechanical loading and metabolic activity. Periods of inactivity, including bed rest, limb immobilization or microgravity, induce a pronounced loss of muscle mass and function. This review examines the mechanistic role of myostatin (growth differentiation factor‐8; GDF‐8), a member of the transforming growth factor‐β superfamily, in mediating inactivity‐induced skeletal muscle atrophy. Accumulating evidence from human and rodent studies demonstrates that physical inactivity upregulates myostatin expression and signalling, shifting muscle protein turnover toward net protein degradation. Mechanistically, myostatin binds to the activin type IIB receptor (ActRIIB) and activates Smad2/3 signalling, which suppresses Akt phosphorylation and downstream mTOR activity, resulting in reduced protein translation. Diminished Akt signalling activates FoxO transcription factors, promoting ubiquitin–proteasome‐mediated proteolysis. In parallel, myostatin maintains satellite cells in a quiescent state, impairing MyoD‐driven activation and limiting myogenesis, thereby reducing regenerative capacity during and after physical inactivity. We provide a narrative mini‐review on the time course of gene expression of myostatin during inactivity. Finally, these mechanistic insights have stimulated therapeutic strategies targeting the myostatin–ActRIIB axis, notably bimagrumab, a monoclonal antibody against ActRIIB and inhibitor of downstream myostatin signalling. Evidence from human and rodent studies suggests that myostatin inhibition may represent a promising strategy to counteract skeletal muscle disuse atrophy caused by inactivity. Collectively, the current evidence highlights myostatin as a central molecular integrator of mechanical unloading‐induced muscle atrophy.
Derk H C Nieuwenhuijsen, M. Eggelbusch, R. Wüst· Experimental Physiology· 0 citations
OBJECTIVES
Patients with long coronavirus disease (COVID) experience disabling fatigue, autonomic dysfunction, reduced exercise capacity and post-exertional malaise (PEM). Heart rate variability (HRV) can evaluate autonomic function and monitor overexertion, potentially helping to mitigate PEM. This study aimed to use continuous multi-day HRV recordings to monitor overexertion and study autonomic function in long COVID.
METHOD
Heart rate and HRV were continuously measured in 121 patients with long COVID (43 ± 11 years, 32% male) and 21 healthy controls (42 ± 13 years, 48% male), with daily life activities tracked in a logbook. Participants underwent a (sub)maximal cardiopulmonary exercise test to determine heart rate at the first ventilatory threshold (VT1) to study HRV responses to exercise at different intensities.
RESULTS AND DISCUSSION
HRV was lower in patients with long COVID compared with healthy controls during various daily activities and sleep (p = 0.027). Across all exercise intensities surrounding the VT1, HRV remained lower for 24 h in patients compared with controls (p = 0.010). Nighttime HRV decreased with intense exercise and longer durations in patients with long COVID (p = 0.018), indicative of exercise-induced diurnal disturbances of the autonomic nervous system in long COVID.
CONCLUSION
Heart rate variability, assessed by wearables, suggests autonomic dysfunction in patients with long COVID. The delayed recovery of the sympathovagal balance after exercise close to and above VT1, suggests that the risk of PEM rises above VT1.
APPLICATION
These results confirm the applicability of wearables to assess autonomic function and manage overexertion in patients with long COVID.
Twan M Ruijgt, Anouk Slaghekke, Anneke Ellens et al.· Sports Medicine· 0 citations
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