Muscle Weakness and the Irisin-BDNF and Oxidative Stress Axis in the 60-Day Pseudorandomised Controlled AGBRESA Bed Rest Study

Kurzfassung

BACKGROUND: Muscle atrophy and weakness are among the most detrimental consequences of disuse, microgravity, hospitalisation and ageing. Oxidative modifications of myofibrillar proteins generated by oxidative stress may contribute to the reduced force- and power-generating capacity of skeletal muscles. As part of the 60-day AGBRESA bed rest (BR) study, we studied (1) how microgravity-induced disuse affected markers of systemic and muscle oxidative stress, (2) how these related to muscle function and (3) to what extent artificial gravity (AG) attenuated these changes. Since the myokine irisin may protect against muscle deterioration in disuse, we additionally assessed serum irisin levels. METHODS: Sixteen men and eight women (33 +/- 9 years) participated in the AGBRESA study. Participants were pseudorandomly assigned to a control group (BR only), or a continuous or intermittent centrifugation group (n = 8 in each group) to assess the efficacy of daily 30-min AG in attenuating the adverse effects of BR-induced disuse. Muscle function, muscle protein carbonyls, serum irisin and key modulators of oxidative stress and cell protection in muscle and blood were assessed before, on Day 6, and at the end of BR. RESULTS: BR caused a reduction in peak torque during maximal voluntary isometric knee extension and knee flexion (p < 0.001) that was greater in women than in men (knee extension, w: -39.7 +/- 3.5%, m: -25.1 +/- 2.4%; knee flexion, w: -32.9 +/- 4.5%, m: -10.2 +/- 3.5%, p </= 0.002) and faster electrically evoked twitch muscle contractions of plantar flexor and knee extensor muscles (half relaxation time and % peak rate of relaxation, p </= 0.003). AG attenuated the BR-induced increase in evoked twitch contraction speed in the knee extensors (group x time interactions: half relaxation time, p = 0.009; % peak rate of relaxation, p = 0.030), and the loss of evoked twitch peak torque of plantar flexors (AG - 25%, Controls -48%, group x time interactions, p = 0.020). Neither BR nor AG affected the circulating levels of systemic oxidative stress and muscle carbonyl concentration and serum irisin levels. However, participants with the highest serum irisin and brain-derived neurotrophic factor levels showed lower levels of 8-iso-PGF2alpha, a marker of systemic oxidative stress (r = -0.486, p = 0.019; r = -0.512, p = 0.012, respectively) and circulating levels of the C-terminal agrin fragment, a biomarker of neuromuscular junction fragmentation. CONCLUSIONS: AG exposure attenuated some of the BR-induced changes in twitch contractile properties. Neither BR nor AG induced significant alterations in systemic oxidative stress, or muscle protein carbonylation, suggesting that the main contribution to the BR-induced loss of muscle strength during the AGBRESA study was not oxidative stress.