Going retro: Oxidative stress biomarkers in modern redox biology.

The field of redox biology is inherently intertwined with oxidative stress biomarkers. Oxidative stress biomarkers have been utilized for many different objectives. Our analysis indicates that oxidative stress biomarkers have several salient applications: (1) diagnosing oxidative stress, (2) pinpointing likely redox components in a physiological or pathological process and (3) estimating the severity, progression and/or regression of a disease. On the contrary, oxidative stress biomarkers do not report on redox signaling. Alternative approaches to gain more mechanistic insights are: (1) measuring molecules that are integrated in pathways linking redox biochemistry with physiology, (2) using the exomarker approach and (3) exploiting -omics techniques. More sophisticated approaches and large trials are needed to establish oxidative stress biomarkers in the clinical setting.

Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle.

Several redox-regulated responses to an acute exercise bout fail in aged animal skeletal muscle, including the ability to upregulate the expression of antioxidant defense enzymes and heat shock proteins (HSPs). These findings are generally derived from studies on sedentary rodent models and thus may be related to reduced physical activity and/or intraspecies differences as opposed to aging per se. This study, therefore, aimed to determine the influence of age and training status on the expression of HSPs, antioxidant enzymes, and NO synthase isoenzymes in quiescent and exercised human skeletal muscle. Muscle biopsy samples were obtained from the vastus lateralis before and 3 days after an acute high-intensity-interval exercise bout in young trained, young untrained, old trained, and old untrained subjects. Levels of HSP72, PRX5, and eNOS were significantly higher in quiescent muscle of older compared with younger subjects, irrespective of training status. 3-NT levels were elevated in muscles of the old untrained but not the old trained state, suggesting that lifelong training may reduce age-related macromolecule damage. SOD1, CAT, and HSP27 levels were not significantly different between groups. HSP27 content was upregulated in all groups studied postexercise. HSP72 content was upregulated to a greater extent in muscle of trained compared with untrained subjects postexercise, irrespective of age. In contrast to every other group, old untrained subjects failed to upregulate CAT postexercise. Aging was associated with a failure to upregulate SOD2 and a downregulation of PRX5 in muscle postexercise, irrespective of training status. In conclusion, lifelong training is unable to fully prevent the progression toward a more stressed muscular state as evidenced by increased HSP72, PRX5, and eNOS protein levels in quiescent muscle. Moreover, lifelong training preserves some (e.g., CAT) but not all (e.g., SOD2, HSP72, PRX5) of the adaptive redox-regulated responses after an acute exercise bout. Collectively, these data support many but not all of the findings from previous animal studies and suggest parallel aging effects in humans and mice at rest and after exercise that are not modulated by training status in human skeletal muscle.

Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function.

The current study implemented a two-part design to (1) assess the vitamin D concentration of a large cohort of non-vitamin D supplemented UK-based athletes and 30 age-matched healthy non-athletes and (2) to examine the effects of 5000 IU · day(-1) vitamin D(3) supplementation for 8-weeks on musculoskeletal performance in a placebo controlled trial. Vitamin D concentration was determined as severely deficient if serum 25(OH)D < 12.5 nmol · l(-1), deficient 12.5-30 nmol · l(-1) and inadequate 30-50 nmol · l(-1). We demonstrate that 62% of the athletes (38/61) and 73% of the controls (22/30) exhibited serum total 25(OH)D < 50 nmol · l(-1). Additionally, vitamin D supplementation increased serum total 25(OH)D from baseline (mean ± SD = 29 ± 25 to 103 ± 25 nmol · l(-1), P = 0.0028), whereas the placebo showed no significant change (53 ± 29 to 74 ± 24 nmol · l(-1), P = 0.12). There was a significant increase in 10 m sprint times (P = 0.008) and vertical-jump (P = 0.008) in the vitamin D group whereas the placebo showed no change (P = 0.587 and P = 0.204 respectively). The current data supports previous findings that athletes living at Northerly latitudes (UK = 53° N) exhibit inadequate vitamin D concentrations (<50 nmol · l(-1)). Additionally the data suggests that inadequate vitamin D concentration is detrimental to musculoskeletal performance in athletes. Future studies using larger athletic groups are now warranted.

PGC-1α transcriptional response and mitochondrial adaptation to acute exercise is maintained in skeletal muscle of sedentary elderly males.

The aim of the present study was to examine the effects of ageing and training status on (1) markers of skeletal muscle mitochondrial content and (2) the ability to activate the acute signalling pathways associated with regulating exercise-induced mitochondrial biogenesis. Muscle biopsies were obtained from the vastus lateralis muscle of young untrained (24 ± 4 years, n = 6; YU), young trained (22 ± 3 years, n = 6; YT), old untrained (65 ± 6 years, n = 6; OU) and old trained (64 ± 3 years, n = 6; OT) healthy males before and after (3 h and 3 days post-exercise) completion of high-intensity interval cycling exercise. In resting muscle, lifelong training preserved mtDNA, PGC-1α and COXIV protein content such that muscles from OT individuals were comparable to muscles from both YU and YT individuals, whereas lifelong sedentary behaviour reduced such markers of mitochondrial content. Regardless of age or training status, acute exercise induced comparable increases in p38MAPK phosphorylation immediately post-exercise, PGC-1α and COXIV mRNA expression at 3 h post-exercise and COXIV protein at 3 days post-exercise. Data demonstrate that lifelong endurance training preserves skeletal muscle PGC-1α content and that despite the mitochondrial dysfunction typically observed with sedentary ageing, muscles from sedentary elderly individuals retain the capacity to activate the acute signalling pathways associated with regulating the early processes of mitochondrial biogenesis. We consider our data to have immediate translational potential as they highlight the potential therapeutic effects of exercise to induce skeletal muscle mitochondrial biogenesis persist late in adulthood, even after a lifetime of physical inactivity.

Vitamin E supplementation does not alter physiological performance at fixed blood lactate concentrations in trained runners.

AIM: The aim of the study was to determine the direction of change in performance variables at fixed blood lactate concentrations following vitamin E (VE) supplementation. METHODS: In a paired-matched design twelve (male: N.=8; female: N.=4) trained runners were allocated to a VE (N.=6; 268 mg·d⁻¹) or placebo (N.=6; glucose: 30 mg·d⁻¹) group for 35 days. Participants completed a discontinuous incremental exercise test, pre and post supplementation, to determine peak oxygen uptake (VO2peak) running velocity and percentage of peak oxygen uptake (%(VO2peak) at the lactate threshold (TLAC) and the onset of blood lactate accumulation (OBLA). Participants maintained a standardised training regime throughout the supplementation period. RESULTS: VE supplementation failed to significantly enhance velocity at TLAC (P=0.91) and OBLA (P=0.22) compared to a placebo treatment. Analogously, VE did not significantly enhance %(VO2peak) at TLAC (P=0.85) and OBLA (P=0.71) compared to a placebo treatment. Whilst VE supplementation did not enhance performance it did not impair performance compared to a placebo. Training significantly enhanced velocity at TLAC (P=0.00) and OBLA (P=0.05). No training-induced improvements in %VO2peak at TLAC (P=0.06) and OBLA (P=0.40) were observed. CONCLUSION: Daily VE supplementation for 35 days does not enhance or impair physiological performance at fixed blood lactate concentrations. Long-term VE supplementation for the purposes of performance enhancement is not recommended.

N-Acetylcysteine Attenuates Fatigue Following Repeated-Bouts of Intermittent Exercise: Practical Implications for Tournament Situations.

Production of reactive oxygen species (ROS) during contractions is associated with muscular fatigue and damage in the short-term and adaptive responses in the long-term. When adaptation is inconsequential acute antioxidant supplementation may be able to attenuate muscle fatigue and damage to enhance performance. This study aimed to determine the effects of acute oral N-acetylcysteine (NAC) supplementation on Yo-Yo intermittent recovery test performance level one (YIRT-L1) following repeated-bouts of damaging intermittent exercise. In a pair-matched design, twelve recreationally-trained males engaged in either six days of NAC (n = 6) or placebo (n = 6) supplementation. Following a treatment loading day, participants completed three testing sessions, on alternate days, consisting of a pre-exercise Isokinetic dynamometry (IKD) test, a damaging intermittent exercise protocol, YIRT-L1 and a post-exercise IKD. A further IKD test was completed on the two intervening days. NAC treatment resulted in a significant preservation of YIRT-L1 performance (P≤0.0005). IKD performance significantly deteriorated over time at all contractions speeds and this deterioration was not influenced by treatment group. Plasma creatine kinase values increased significantly over time (P=.002) and were significantly greater in the NAC group compared with the placebo group (P=.029). NAC induced mild-gastrointenstinal side effects. NAC supplementation may be a useful strategy to enhance performance during short-term competitive situations where adaption is inconsequential. Titration studies to elucidate a treatment dose that enhances performance without inducing side-effects are now required.