Redox signaling and skeletal muscle adaptation during aerobic exercise.

Redox regulation is a fundamental physiological phenomenon related to oxygen-dependent metabolism, and skeletal muscle is mainly regarded as a primary site for oxidative phosphorylation. Several studies have revealed the importance of reactive oxygen and nitrogen species (RONS) in the signaling process relating to muscle adaptation during exercise. To date, improving knowledge of redox signaling in modulating exercise adaptation has been the subject of comprehensive work and scientific inquiry. The primary aim of this review is to elucidate the molecular and biochemical pathways aligned to RONS as activators of skeletal muscle adaptation and to further identify the interconnecting mechanisms controlling redox balance. We also discuss the RONS-mediated pathways during the muscle adaptive process, including mitochondrial biogenesis, muscle remodeling, vascular angiogenesis, neuron regeneration, and the role of exogenous antioxidants.

Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function.

We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015-0.044). This was associated with a general net cerebral output (v > a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a > v) and global cerebral blood flow (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative-nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative-nitrosative stress. KEY POINTS: Local sampling of blood across the cerebral circulation in ultra-elite apnoeists determined the extent to which severe end-apnoea hypoxaemic hypercapnia (prior normoxic normoventilation) and hyperoxaemic hypercapnia (prior hyperoxic hyperventilation) impact free radical-mediated nitric oxide bioavailability and global cerebral bioenergetic function. Apnoea generally increased the net cerebral output of free radicals and suppressed plasma nitrite consumption, thereby reducing delivery of nitric oxide consistent with elevated oxidative-nitrosative stress. The apnoea-induced elevation in global cerebral blood flow was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose. Cerebral oxidative-nitrosative stress was greater during hypoxaemic hypercapnia compared with hyperoxaemic hypercapnia and coincided with a lower apnoea-induced elevation in global cerebral blood flow, highlighting a key catalytic role for hypoxaemia. This applied model of voluntary human asphyxia might have broader implications for the management and treatment of neurological diseases characterized by extremes of oxygen demand and carbon dioxide production.

Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle.

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

A systematic review and meta-analysis of the SIRT1 response to exercise.

Sirtuin 1 (SIRT1) is a key physiological regulator of metabolism and a target of therapeutic interventions for cardiometabolic and ageing-related disorders. Determining the factors and possible mechanisms of acute and adaptive SIRT1 response to exercise is essential for optimising exercise interventions aligned to the prevention and onset of disease. Exercise-induced SIRT1 upregulation has been reported in animals, but, to date, data in humans have been inconsistent. This exploratory systematic review and meta-analysis aims to assess various exercise interventions measuring SIRT1 in healthy participants. A total of 34 studies were included in the meta-analysis (13 single bout exercise, 21 training interventions). Studies were grouped according to tissue sample type (blood, muscle), biomarkers (gene expression, protein content, enzyme level, enzyme activity), and exercise protocols. A single bout of high-intensity or fasted exercise per se increases skeletal muscle SIRT1 gene expression as measured by qPCR or RT-PCR, while repeated resistance training alone increases blood SIRT1 levels measured by ELISA. A limited number of studies also show a propensity for an increase in muscle SIRT1 activity as measured by fluorometric or sirtuin activity assay. In conclusion, exercise acutely upregulates muscle SIRT1 gene expression and chronically increases SIRT1 blood enzyme levels.

Proof of concept of prehabilitation: a combination of education and behavioural change, to promote physical activity in people with fibromyalgia.

OBJECTIVES: To establish proof of concept of a prehabilitation intervention, a combination of education and behavioural change, preceding a physical activity programme in people with fibromyalgia (FM). SETTINGS: Open-label, feasibility clinical trial. PARTICIPANTS: Eleven people with FM (10 women). INTERVENTIONS: The prehabilitation intervention consisted of 4 weeks, 1 weekly session (~1 to 1.5 hours), aimed to increase self-efficacy and understand why and how to engage in a gentle and self-paced physical activity programme (6 weeks of walking with telephone support). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the acceptability and credibility of the intervention by means of the Credibility/Expectancy Questionnaire. Secondary outcomes comprised scales to measure FM severity, specific symptoms and sedentary behaviour. An exit interview was conducted to identify the strengths and weaknesses and barriers to the intervention. RESULTS: One participant dropped out due to finding the walking programme excessively stressful. Participants expected the intervention would improve their symptoms by 22%-38% but resulted in 5%-26% improvements. Participants would be confident in recommending this intervention to a friend who experiences similar problems. The interviews suggested that the fluctuation of symptoms should be considered as an outcome and that the prehabilitation intervention should accomodate these fluctuation. Additional suggestions were to incorporate initial interviews (patient-centred approach), to tailor the programmes to individuals' priorities and to offer a variety of physical activity programmes to improve motivation. CONCLUSIONS: This feasibility study demonstrated that our novel approach is acceptable to people with FM. Future interventions should pay attention to flexibility, symptoms fluctuation and patients support. TRIAL REGISTRATION NUMBER: NCT03764397.

Astaxanthin promotes mitochondrial biogenesis and antioxidant capacity in chronic high-intensity interval training.

PURPOSE: Reactive oxygen and nitrogen species are required for exercise-induced molecular adaptations; however, excessive exercise may cause cellular oxidative distress. We postulate that astaxanthin (ASX) can neutralize oxidative distress and stimulate mitochondrial biogenesis in high-intensity exercise-trained mice. METHODS: Six-week-old mice (n = 8/group) were treated with ASX (10 mg/kg BW) or placebo. Training groups participated in 30 min/day high-intensity interval training (HIIT) for 6 weeks. Gastrocnemius muscle was collected and assayed following the exercise training period. RESULTS: Compared to the HIIT control mice, the ASX-treated HIIT mice reduced malonaldehyde levels and upregulated the expression of Nrf2 and FOXO3a. Meanwhile, the genes NQO1 and GCLC, modulated by Nrf2, and SOD2, regulated by FOXO3a, and GPx4, were transcriptionally upregulated in the ASX-treated HIIT group. Meanwhile, the expression of energy sensors, AMPK, SIRT1, and SIRT3, increased in the ASX-treated HIIT group compared to the HIIT control group. Additionally, PGC-1α, regulated by AMPK and SIRT1, was upregulated in the ASX-treated HIIT group. Further, the increased PGC-1α stimulated the transcript of NRF1 and Tfam and mitochondrial proteins IDH2 and ATP50. Finally, the ASX-treated HIIT mice had upregulations in the transcript level of mitochondrial fusion factors, including Mfn1, Mfn2, and OPA1. However, the protein level of AMPK, SIRT1, and FOXO3a, and the transcript level of Nrf2, NQO1, PGC-1α, NRF1, Mfn1, Mfn2, and OPA1 decreased in the HIIT control group compared to the sedentary control group. CONCLUSION: Supplementation with ASX can reduce oxidative stress and promote antioxidant capacity and mitochondrial biogenesis during strenuous HIIT exercise in mice.

Exercise, type 1 diabetes mellitus and blood glucose: The implications of exercise timing.

The scientific literature shows that exercise has many benefits for individuals with type 1 diabetes. Yet, several barriers to exercise in this population exist, such as post-exercise hypoglycaemia or hyperglycaemia. Several studies suggest that the timing of exercise may be an important factor in preventing exercise-induced hypoglycaemia or hyperglycaemia. However, there is a paucity of evidence solely focused on summarising findings regarding exercise timing and the impact it has on glucose metabolism in type 1 diabetes. This report suggests that resistance or high-intensity interval exercise/training (often known as HIIT) may be best commenced at the time of day when an individual is most likely to experience a hypoglycaemic event (i.e., afternoon/evening) due to the superior blood glucose stability resistance and HIIT exercise provides. Continuous aerobic-based exercise is advised to be performed in the morning due to circadian elevations in blood glucose at this time, thereby providing added protection against a hypoglycaemic episode. Ultimately, the evidence concerning exercise timing and glycaemic control remains at an embryonic stage. Carefully designed investigations of this nexus are required, which could be harnessed to determine the most effective, and possibly safest, time to exercise for those with type 1 diabetes.

Oxidative Stress and Exercise.

It is now well-established that regular moderate-intensity exercise training can activate salient cell adaptive properties, leading to a state of oxidative eustress [...].

Circadian Clocks, Redox Homeostasis, and Exercise: Time to Connect the Dots?

Compelling research has documented how the circadian system is essential for the maintenance of several key biological processes including homeostasis, cardiovascular control, and glucose metabolism. Circadian clock disruptions, or losses of rhythmicity, have been implicated in the development of several diseases, premature ageing, and are regarded as health risks. Redox reactions involving reactive oxygen and nitrogen species (RONS) regulate several physiological functions such as cell signalling and the immune response. However, oxidative stress is associated with the pathological effects of RONS, resulting in a loss of cell signalling and damaging modifications to important molecules such as DNA. Direct connections have been established between circadian rhythms and oxidative stress on the basis that disruptions to circadian rhythms can affect redox biology, and vice versa, in a bi-directional relationship. For instance, the expression and activity of several key antioxidant enzymes (SOD, GPx, and CAT) appear to follow circadian patterns. Consequently, the ability to unravel these interactions has opened an exciting area of redox biology. Exercise exerts numerous benefits to health and, as a potent environmental cue, has the capacity to adjust disrupted circadian systems. In fact, the response to a given exercise stimulus may also exhibit circadian variation. At the same time, the relationship between exercise, RONS, and oxidative stress has also been scrutinised, whereby it is clear that exercise-induced RONS can elicit both helpful and potentially harmful health effects that are dependent on the type, intensity, and duration of exercise. To date, it appears that the emerging interface between circadian rhythmicity and oxidative stress/redox metabolism has not been explored in relation to exercise. This review aims to summarise the evidence supporting the conceptual link between the circadian clock, oxidative stress/redox homeostasis, and exercise stimuli. We believe carefully designed investigations of this nexus are required, which could be harnessed to tackle theories concerned with, for example, the existence of an optimal time to exercise to accrue physiological benefits.

Exercise decreases PP2A-specific reversible thiol oxidation in human erythrocytes: Implications for redox biomarkers.

New readily accessible systemic redox biomarkers are needed to understand the biological roles reactive oxygen species (ROS) play in humans because overtly flawed, technically fraught, and unspecific assays severely hamper translational progress. The antibody-linked oxi-state assay (ALISA) makes it possible to develop valid ROS-sensitive target-specific protein thiol redox state biomarkers in a readily accessible microplate format. Here, we used a maximal exercise bout to disrupt redox homeostasis in a physiologically meaningful way to determine whether the catalytic core of the serine/threonine protein phosphatase PP2A is a candidate systemic redox biomarker in human erythrocytes. We reasoned that: constitutive oxidative stress (e.g., haemoglobin autoxidation) would sensitise erythrocytes to disrupted ion homeostasis as manifested by increased oxidation of the ion regulatory phosphatase PP2A. Unexpectedly, an acute bout of maximal exercise lasting ~16 min decreased PP2A-specific reversible thiol oxidation (redox ratio, rest: 0.46; exercise: 0.33) without changing PP2A content (rest: 193 pg/ml; exercise: 191 pg/ml). The need for only 3-4 µl of sample to perform ALISA means PP2A-specific reversible thiol oxidation is a capillary-fingertip blood-compatible candidate redox biomarker. Consistent with biologically meaningful redox regulation, thiol reductant-inducible PP2A activity was significantly greater (+10%) at rest compared to exercise. We establish a route to developing new readily measurable protein thiol redox biomarkers for understanding the biological roles ROS play in humans.

"Why would you not listen? It is like being given the winning lottery numbers and deciding not to take them": semi-structured interviews with post-acute myocardial infarction patients and their significant others exploring factors that influence participation in cardiac rehabilitation and long-term exercise training.

PURPOSE: Despite the clinical benefits, coronary artery disease patient participation rates in cardiac rehabilitation (CR) and long-term exercise are poor. This study explored the factors related to participation in these interventions from the perspectives of post-acute myocardial infarction (AMI) patients and their significant others. METHODS: Semi-structured interviews were performed with post-AMI patients (number (n) = 10) and their significant others (n = 10) following phase-III and phase-IV CR. Reflexive thematic analysis with an inductive orientation was utilised to identify themes within the dataset (ClinicalTrials.gov identifier: NCT03907293). RESULTS: The overarching theme of the data was a perceived need to improve health, with the participants viewing health benefits as the principal motive for participating in CR and long-term exercise training. Three further themes were identified: motivation, extrinsic influences, and CR experience. These themes captured the underlying elements of the participants' decision to take part in CR and long-term exercise training for the purpose of health improvements. CONCLUSION: An AMI collectively impacts the attitudes and beliefs of patients and their significant others in relation to CR participation, long-term exercise, and health. The factors identified in this study may inform strategies to promote patient enrollment in CR and adherence to long-term exercise.IMPLICATIONS FOR REHABILITATIONPost-AMI patients and their significant others reported that health benefits were the primary motive for participating in CR and long-term exercise, with aspects related to motivation, extrinsic influences, and CR experience underpinning the decision.Healthcare professionals should supply information about health benefits during the CR referral process, with insights into the experiences of CR graduates potentially improving the strength of recommendation.CR facilitators may promote long-term exercise adherence by assisting patients with the identification of an enjoyable exercise modality.Healthcare professionals should include significant others in the CR referral process, which may enable these individuals to support the patients' decisions.

Exercise and Cardioprotection in Coronary Artery Disease: A Pilot Quasi-Experimental Study.

Sirtuin-1 is a protein that may orchestrate the cardioprotective effect of exercise by controlling cellular processes. This pilot study assessed the feasibility of performing a quasi-experimental study in this area. Patients with postacute myocardial infarction were recruited across four hospital sites in the United Kingdom. The participants were offered one weekly exercise session at Phase-III and Phase-IV cardiac rehabilitation (CR). Measurements were obtained pre-Phase-III CR (Week 1), post-Phase-III CR (Week 8), and post-Phase-IV CR (Week 22). Twenty-eight patients were recruited (79% male, 100% White, 60.2 ± 10.5 years old). The recruitment rate was not fulfilled (<70% eligible patients recruited; 0.9 participants recruited per week over 30 weeks). The success criteria for dropout rate, adherence rate, and collection of sirtuin-1 measures were satisfied. A large increase in sirtuin-1 (0.14 ± 0.03, d ≥ 0.8) was seen after Phase-III and Phase-IV CR. Collectively, a quasi-experimental study is feasible with a revised recruitment strategy.

Music Tempo: A Tool for Regulating Walking Cadence and Physical Activity Intensity in Overweight Adults?

This study investigated if music tempo can prompt a desired walking cadence, and if music can provide a stimulus to regulate physical activity intensity in a longitudinal physical activity intervention with free-living adults. Overweight adults (n = 37; 94.26 ± 17.11 kg; 49.63 ± 12.37 years) were randomly assigned to an intervention (IG, n = 17) or usual care group (UC, n = 20) as part of a novel nine-month walking intervention. IG participants walked to self-selected music with a predetermined tempo and received a behavioural change support programme. At baseline, four-, six- and nine-months participants were asked to walk around an elliptical track at their habitual pace (0-2 min) and then in time to a predetermined tempo (2-8 min) designed to elicit moderate intensity. Cadence response (steps/min) was assessed and intensity (heart rate (bpm) recorded using wireless telemetry. A repeated measures general linear model (GLM) examined differences between groups over time (p < 0.05). All data is presented as means ± SD. At each assessment point both groups displayed an immediate cadence adjustment in response to music tempo (p < 0.01) i.e., habitual cadence vs. 3 METs target cadence (p < 0.05) and 3 METs target cadence vs. 5 METs target cadence (p < 0.05). Additionally, IG participants displayed an increased habitual cadence (0-2 min) at each assessment point (p < 0.05; 110 ± 9, 121.80 ± 7.5, 121.46 ± 10, 121.93 ± 7 steps/min respectively). UC participant's habitual cadence was unchanged from 0-9 months (p > 0.05; 120 ± 10, 116 ± 13, 119 ± 12 and 119 ± 9 steps/min respectively). Music tempo may be a useful regulatory tool to prompt the free-living individual to reach an appropriate stride rate to achieve a walking pace that is at least moderate intensity. It also appears that results may be trainable as throughout the study an increased habitual walking cadence was observed, in the absence of music.

The metabolic-epigenetic nexus in type 2 diabetes mellitus.

The prevalence of type 2 diabetes mellitus (T2DM) continues to rise globally. Yet the aetiology and pathophysiology of this noncommunicable, polygenic disease, is poorly understood. Lifestyle factors, such as poor dietary intake, lack of exercise, and abnormal glycaemia, are purported to play a role in disease onset and progression, and these environmental factors may disrupt specific epigenetic mechanisms, leading to a reprogramming of gene transcription. The hyperglycaemic cell per se, alters epigenetics through chemical modifications to DNA and histones via metabolic intermediates such as succinate, α-ketoglutarate and O-GlcNAc. To illustrate, α-ketoglutarate is considered a salient co-factor in the activation of the ten-eleven translocation (TET) dioxygenases, which drives DNA demethylation. On the contrary, succinate and other mitochondrial tricarboxylic acid cycle intermediates, inhibit TET activity predisposing to a state of hypermethylation. Hyperglycaemia depletes intracellular ascorbic acid, and damages DNA by enhancing the production of reactive oxygen species (ROS); this compromised cell milieu exacerbates the oxidation of 5-methylcytosine alongside a destabilisation of TET. These metabolic connections may regulate DNA methylation, affecting gene transcription and pancreatic islet ß-cell function in T2DM. This complex interrelationship between metabolism and epigenetic alterations may provide a conceptual foundation for understanding how pathologic stimuli modify and control the intricacies of T2DM. As such, this narrative review will comprehensively evaluate and detail the interplay between metabolism and epigenetic modifications in T2DM.

Objectively quantified physical activity and sedentary behaviour in a young UAE population.

OBJECTIVES: There is a lack of public awareness of the importance of engaging in physical activity (PA) in the United Arab Emirates (UAE). Nearly 58% of the UAE adult population self-reports as being physically inactive although little accelerometer data currently exists. The aim of this study was to obtain the first dataset that objectively quantifies PA and sedentary behaviour (SB) in young UAE adults. METHODS: This cross-sectional study recruited 140 university students. Body composition and accelerometry was assessed using a Tanita body composition analyser and ActiGraph accelerometer. Differences (p≤0.05) between gender (male vs female) and body mass index (normal vs overweight/obese) were determined using independent samples t-tests and χ2 tests for nominal variables. RESULTS: Both males and females spent high amounts of time in SB, encompassing ~80% of waking hours. PA was primarily light intensity (14.1%), although males spent significantly greater time in moderate-to-vigorous intensity activity. Moreover, 50% of males compared with 76.6% of females were classified as sedentary/low active according to daily step counts. CONCLUSION: Our data provide evidence of high levels of SB among young adults in the UAE with PA being predominantly light intensity, therefore, both PA and SB should be carefully monitored in this country.

Effectiveness of Exercise on Fatigue and Sleep Quality in Fibromyalgia: A Systematic Review and Meta-analysis of Randomized Trials.

OBJECTIVES: To determine the effects of exercise on fatigue and sleep quality in fibromyalgia (primary aim) and to identify which type of exercise is the most effective in achieving these outcomes (secondary aim). DATA SOURCES: PubMed and Web of Science were searched from inception until October 18, 2018. STUDY SELECTION: Eligible studies contained information on population (fibromyalgia), intervention (exercise), and outcomes (fatigue or sleep). Randomized controlled trials (RCT) testing the effectiveness of exercise compared with usual care and randomized trials (RT) comparing the effectiveness of 2 different exercise interventions were included for the primary and secondary aims of the present review, respectively. Two independent researchers performed the search, screening, and final eligibility of the articles. Of 696 studies identified, 17 RCTs (n=1003) were included for fatigue and 12 RCTs (n=731) for sleep. Furthermore, 21 RTs compared the effectiveness of different exercise interventions (n=1254). DATA EXTRACTION: Two independent researchers extracted the key information from each eligible study. DATA SYNTHESIS: Separate random-effect meta-analyses were performed to examine the effects from RCTs and from RTs (primary and secondary aims). Standardized mean differences (SMD) effect sizes were calculated using Hedges' adjusted g. Effect sizes of 0.2, 0.4, and 0.8 were considered small, moderate, and large. Compared with usual care, exercise had moderate effects on fatigue and a small effect on sleep quality (SMD, -0.47; 95% confidence interval [CI], -0.67 to -0.27; P<.001 and SMD, -0.17; 95% CI, -0.32 to -0.01; P=.04). RTs in which fatigue was the primary outcome were the most beneficial for lowering fatigue. Additionally, meditative exercise programs were the most effective for improving sleep quality. CONCLUSIONS: Exercise is moderately effective for lowering fatigue and has small effects on enhancing sleep quality in fibromyalgia. Meditative exercise programs may be considered for improving sleep quality in fibromyalgia.

Targeted Antioxidants in Exercise-Induced Mitochondrial Oxidative Stress: Emphasis on DNA Damage.

Exercise simultaneously incites beneficial (e.g., signal) and harming (e.g., damage to macromolecules) effects, likely through the generation of reactive oxygen and nitrogen species (RONS) and downstream changes to redox homeostasis. Given the link between nuclear DNA damage and human longevity/pathology, research attempting to modulate DNA damage and restore redox homeostasis through non-selective pleiotropic antioxidants has yielded mixed results. Furthermore, until recently the role of oxidative modifications to mitochondrial DNA (mtDNA) in the context of exercising humans has largely been ignored. The development of antioxidant compounds which specifically target the mitochondria has unveiled a number of exciting avenues of exploration which allow for more precise discernment of the pathways involved with the generation of RONS and mitochondrial oxidative stress. Thus, the primary function of this review, and indeed its novel feature, is to highlight the potential roles of mitochondria-targeted antioxidants on perturbations to mitochondrial oxidative stress and the implications for exercise, with special focus on mtDNA damage. A brief synopsis of the current literature addressing the sources of mitochondrial superoxide and hydrogen peroxide, and available mitochondria-targeted antioxidants is also discussed.

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage.

High-intensity exercise damages mitochondrial DNA (mtDNA) in skeletal muscle. Whether MitoQ - a redox active mitochondrial targeted quinone - can reduce exercise-induced mtDNA damage is unknown. In a double-blind, randomized, placebo-controlled design, twenty-four healthy male participants consisting of two groups (placebo; n = 12, MitoQ; n = 12) performed an exercise trial of 4 x 4-min bouts at 90-95% of heart rate max. Participants completed an acute (20 mg MitoQ or placebo 1-h pre-exercise) and chronic (21 days of supplementation) phase. Blood and skeletal muscle were sampled immediately pre- and post-exercise and analysed for nuclear and mtDNA damage, lipid hydroperoxides, lipid soluble antioxidants, and the ascorbyl free radical. Exercise significantly increased nuclear and mtDNA damage across lymphocytes and muscle (P < 0.05), which was accompanied with changes in lipid hydroperoxides, ascorbyl free radical, and α-tocopherol (P < 0.05). Acute MitoQ treatment failed to impact any biomarker likely due to insufficient initial bioavailability. However, chronic MitoQ treatment attenuated nuclear (P < 0.05) and mtDNA damage in lymphocytes and muscle tissue (P < 0.05). Our work is the first to show a protective effect of chronic MitoQ supplementation on the mitochondrial and nuclear genomes in lymphocytes and human muscle tissue following exercise, which is important for genome stability.