Skeletal muscle mitochondrial H₂O₂ emission increases with immobilization and decreases after aerobic training in young and older men

Abstract

Key pointsr Currently, it is not known whether impaired mitochondrial function contributes to human ageing or whether potential impairments in mitochondrial function with age are secondary to physical inactivity.r The present study investigated mitochondrial respiratory function and reactive oxygen species emission at a predefined membrane potential in young and older men subjected to 2 weeks of one-leg immobilization followed by 6 weeks of aerobic cycle training.r Immobilization increased reactive oxygen species emission and decreased ATP generating respiration. Subsequent aerobic training reversed these effects.r By contrast, age had no effect on the measured variables. r The results of the present study support the notion that increased mitochondrial reactive oxygen species production mediates the detrimental effects seen after physical inactivity and that ageing per se does not cause mitochondrial dysfunction.Abstract Mitochondrial dysfunction, defined as increased oxidative stress and lower capacity for energy production, may be seen with ageing and may cause frailty, or it could be that it is secondary to physical inactivity. We studied the effect of 2 weeks of one-leg immobilization followed by 6 weeks of supervised cycle training on mitochondrial function in 17 young (mean ± SEM: 23 ± 1 years) and 15 older (68 ± 1 years) healthy men. Submaximal H 2 O 2 emission and respiration were measured simultaneously at a predefined membrane potential in isolated mitochondria from skeletal muscle using two protocols: pyruvate + malate (PM) and succinate + rotenone (SR). This allowed measurement of leak and ATP generating respiration from which the coupling efficiency can be calculated. The protein content of the anti-oxidants manganese superoxide dismuthase (MnSOD), CuZn superoxide dismuthase, catalase and gluthathione peroxidase 1 was measured by western blotting. Immobilization decreased ATP generating respiration using PM and increased H 2 O 2 emission using both PM and SR similarly in young and older men. Both were restored to baseline after the training period. Furthermore, MnSOD and catalase content increased with endurance training. The young men had a higher leak respiration at inclusion using PM and a higher membrane potential in State 3 using both substrate combinations. Collectively, the findings of the present study support the notion that increased mitochondrial reactive oxygen species mediates the detrimental effects seen after physical inactivity. Age, on the other hand, was not associated with impairments in anti-oxidant protein levels, mitochondrial respiration or H 2 O 2 emission using either protocol.

Living in flowing water increases resistance to ultraviolet B radiation

“…In humans, chronic exercise caused similar increases in antioxidant capacities and reduced ROS damage, and one of the recognised benefits of regular exercise is that it reduces oxidative stress (Gram et al, 2015;Radak et al, 2013). Our results indicate that the transfer of the increased antioxidant capacity to improve resilience to the negative effects of UV-B radiation is an additional benefit of regular exercise beyond its direct health-promoting effects (Booth et al, 2012;Hawley and Holloszy, 2009;Joseph et al, 2016).…”

“…Physical activity increases ROS production by contracting muscle acutely (Powers and Jackson, 2008). However, chronic low-to midlevel physical activity (exercise) increases antioxidant defences, such that oxidative stress is reduced with chronic exercise (Gram et al, 2015;Radak et al, 2013). Defences against oxidative stress in muscle include enzymatic antioxidants like superoxide dismutase (SOD) and catalase (CAT), and non-enzymatic ROS scavengers such as glutathione (GSH; Sen, 1995;Steinbacher and Eckl, 2015).…”

From physical inactivity to immobilization: Dissecting the role of oxidative stress in skeletal muscle insulin resistance and atrophy

“…Mitochondria contributes to muscle ROS production during immobilization [52, [54][55][56], but other studies highlight that XO plays also an important role [57,58]. To the best of our knowledge no studies reported that NOX, NOS or ER plays a role in the production of ROS induced by immobilization.…”

“…Data from animals, and more recently from humans, indicate that immobilization increases O 2 -and H 2 O 2 emissions in skeletal muscle [52][53][54][55][56]. Mitochondria contributes to muscle ROS production during immobilization [52, [54][55][56], but other studies highlight that XO plays also an important role [57,58].…”

UV-B exposure reduces locomotor performance by impairing muscle function but not mitochondrial ATP production

“…Increased ROS generation is a significant component of UV-B-induced damage to cells (Gniadecki et al, 2001;Ichihashi et al, 2003;Paz et al, 2008;Birch-Machin and Swalwell, 2010). Excess ROS can have detrimental effects on muscle function and metabolism, thereby impacting performance of animals under natural conditions (Kuwahara et al, 2010;Gram et al, 2015). However, the mechanistic pathways by which UV-B-induced ROS affect animal performance remain unsolved.…”