Lifestyle interventions, including exercise and dietary supplementation, can modify DNA methylation and exert health benefits; however, the underlying mechanisms are poorly understood. Here we investigated the impact of acute aerobic exercise and the supplementation of omega-3 polyunsaturated fatty acids (n-3 PUFA) and extra virgin olive oil (EVOO) on global and gene-specific (PPARGC1A, IL6 and TNF) DNA methylation, and DNMT mRNA expression in leukocytes of disease-free individuals. Eight trained male cyclists completed an exercise test before and after a four-week supplementation of n-3 PUFA and EVOO in a double-blind, randomised, repeated measures design. Exercise triggered global hypomethylation (Pre 79.2%; Post 78.7%; p = 0.008), alongside, hypomethylation (Pre 6.9%; Post 6.3%; p < 0.001) and increased mRNA expression of PPARGC1A (p < 0.001). Associations between PPARGC1A methylation and exercise performance were also detected. An interaction between supplement and trial was detected for a single CpG of IL6 indicating increased DNA methylation following n-3 PUFA and decreased methylation following EVOO (p = 0.038). Global and gene-specific DNA methylation associated with markers of inflammation and oxidative stress. The supplementation of EVOO reduced DNMT1 mRNA expression compared to n-3 PUFA supplementation (p = 0.048), whereas, DNMT3a (p = 0.018) and DNMT3b (p = 0.046) mRNA expression were decreased following exercise. In conclusion, we demonstrate that acute exercise and dietary supplementation of n-3 PUFAs and EVOO induce DNA methylation changes in leukocytes, potentially via the modulation of DNMT mRNA expression. Future studies are required to further elucidate the impact of lifestyle interventions on DNA methylation.

Background: Female athletic performance and injury risk is impacted by variations in the menstrual cycle (MC), but the understanding of the impacts and mechanisms influenced by the menstrual cycle on exercise performance are not fully delineated. Aims and Objectives: Evaluate associations between the menstrual cycle, perceived performance, and injury risk of elite female rugby players using an online survey. Methods: An anonymous online questionnaire was completed by 150 elite female rugby players from two English rugby leagues, the Betfred Women’s Super League (BWSL) and the Allianz Premier 15s (AP15s). The collected data were analysed thematically. Results: The Chi-square test was used to assess associations between age groups and contraception usage, weight change, and training and playing performance; none of the associations were statistically significant (all p values > 0.05). Thematic analysis of 11,660 words of data revealed four themes: (a) MC impact on training and competition, (b) education and period management plans, (c) openness of conversations and comfort taking time off, and (d) injury risk. The impacted performance areas were physical (83.7%), psychological (85.7%), and nutritional (80.3%); players experienced decreased appetite, nausea, fatigue, strength declines, heighted emotions, and worsened focus. In total, 87.8% of athletes perceived the MC to negatively impact performance, 85.7% of players desired to be educated further to prevent injuries, improve nutrition, and training adaptions, 51.7% of participants perceived risk of injury to be higher during MC, and 86.4% of participants did not feel comfortable taking time off due to the MC, worrying that selection would be affected and about opinions from others. Conclusion: A clear negative impact on perceived performance and injury risk was reported by survey participants. The interaction of physical, psychological, and nutritional factors, and a lack of awareness and education emphasise the need for further comprehensive studies and interventions, with measures such as MC monitoring and profiling, education, and training adaptions to develop openness, knowledge, and understanding.

Redox enzymes modulate intracellular redox balance and are secreted in response to cellular oxidative stress, potentially modulating systemic inflammation. Both aerobic and resistance exercise are known to cause acute systemic oxidative stress and inflammation; however, how redox enzyme concentrations alter in extracellular fluids following bouts of either type of exercise is unknown. Recreationally active men (n = 26, mean ± SD: age 28 ± 8 yr) took part in either: 1) two separate energy-matched cycling bouts: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE) or 2) an eccentric-based resistance exercise protocol (RES). Alterations in plasma (study 1) and serum (study 2) peroxiredoxin (PRDX)-2, PRDX-4, superoxide dismutase-3 (SOD3), thioredoxin (TRX-1), TRX-reductase and interleukin (IL)-6 were assessed before and at various timepoints after exercise. There was a significant increase in SOD3 (+1.5 ng/mL) and PRDX-4 (+5.9 ng/mL) concentration following HIIE only, peaking at 30- and 60-min post-exercise respectively. TRX-R decreased immediately and 60 min following HIIE (−7.3 ng/mL) and MOD (−8.6 ng/mL), respectively. In non-resistance trained men, no significant changes in redox enzyme concentrations were observed up to 48 h following RES, despite significant muscle damage. IL-6 concentration increased in response to all trials, however there was no significant relationship between absolute or exercise-induced changes in redox enzyme concentrations. These results collectively suggest that HIIE, but not MOD or RES increase the extracellular concentration of PRDX-4 and SOD3. Exercise-induced changes in redox enzyme concentrations do not appear to directly relate to systemic changes in IL-6 concentration. NEW & NOTEWORTHY Two studies were conducted to characterize changes in redox enzyme concentrations after single bouts of exercise to investigate the emerging association between extracellular redox enzymes and inflammation. We provide evidence that SOD3 and PRDX-4 concentration increased following high-intensity aerobic but not eccentric-based resistance exercise. Changes were not associated with IL-6. The results provide a platform to investigate the utility of SOD3 and PRDX-4 as biomarkers of oxidative stress following exercise.

Background: Globally, type 2 diabetes mellitus (T2DM) is one of the fastest-growing noncommunicable multifactorial and polygenic diseases, which leads to many health complications and significant morbidity and mortality. South Asians have a high genetic predisposition to T2DM, with India being home to one in six diabetics. This study investigates the association of selected genetic polymorphisms with T2DM risk and develops a polygenic risk score (PRS). Methods: A case–control study recruited fully consented participants from a population of Jat Sikhs in north India. DNA samples were genotyped for a range of polymorphisms and odds ratios were calculated under several genetic association models. Receiver operating characteristic (ROC) curves were produced for combinations of the PRS and clinical parameters. Results: The GSTT1(rs17856199), GSTM1(rs366631), GSTP1(rs1695), KCNQ1(rs2237892), ACE(rs4646994), and TCF7L2(rs12255372; rs7903146; rs7901695) polymorphisms were associated with increased T2DM risk (p ≤ 0.05). No association was observed with IGF2BP2(rs4402960) or PPARG2(rs1801282). The weighted PRS was found to be significantly higher in patients (mean = 15.4, SD = 3.24) than controls (mean = 11.9, SD = 3.06), and t₍₄₅₄₎ = −12.2 (p < 0.001). The ROC curve analysis found the weighted PRS in combination with clinical variables to be the most effective predictor of T2DM (area under the curve = 0.844, 95%CI = 0.0.808–0.879). Conclusions: Several polymorphisms were associated with T2DM risk. PRS based on even a limited number of loci improves the prediction of the disease. This may provide a useful method for determining T2DM susceptibility for clinical and public health applications.

Telomere dynamics are an active biological process and positive lifestyle factors such as exercise are proposed to potentiate their length. The aim of this study was to investigate the effect of a low-resistance, high-repetition resistance training intervention on leukocyte telomere length (LTL) and associated health parameters. 23 sedentary middle-aged adults volunteered for this study (16 female/7 male; age = 51.5 ± 4.9 years) and performed two one-hour sessions of Les Mills BODYPUMP™ per week for 12 weeks. Outcome measures were taken at baseline, after the training intervention and at 12-month follow-up. LTL remained unchanged following the training intervention (pre 0.819 ± 0.121 vs post 0.812 ± 0.114, p = 0.420), despite a borderline significant increase in hTERT expression (p = 0.050). Circulating levels of tumour necrosis factor alpha were reduced after the intervention (p = 0.001). At 12-month follow-up, subjects who returned to a sedentary lifestyle (n = 10) displayed shorter telomeres compared to their pre (p = 0.036) values. In conclusion, no changes were observed in LTL following the 12-week training intervention, despite improvements in molecular parameters associated with telomere dynamics. It appears continued long-term exercise (>12 months) is necessary to preserve LTL in previously sedentary individuals.

Physical inactivity and a poor diet increase systemic inflammation, while chronic inflammation can be reduced through exercise and nutritional interventions. The mechanisms underlying the impacts of lifestyle interventions on inflammation remain to be fully explained; however, epigenetic modifications may be critical. The purpose of our study was to investigate the impacts of eccentric resistance exercise and fatty acid supplementation on DNA methylation and mRNA expression of TNF and IL6 in skeletal muscle and leukocytes. Eight non-resistance exercise-trained males completed three bouts of isokinetic eccentric contractions of the knee extensors. The first bout occurred at baseline, the second occurred following a three-week supplementation of either omega-3 polyunsaturated fatty acid or extra virgin olive oil and the final bout occurred after eight-weeks of eccentric resistance training and supplementation. Acute exercise decreased skeletal muscle TNF DNA methylation by 5% (p = 0.031), whereas IL6 DNA methylation increased by 3% (p = 0.01). Leukocyte DNA methylation was unchanged following exercise (p > 0.05); however, three hours post-exercise the TNF DNA methylation decreased by 2% (p = 0.004). In skeletal muscle, increased TNF and IL6 mRNA expression levels were identified immediately post-exercise (p < 0.027); however, the leukocyte mRNA expression was unchanged. Associations between DNA methylation and markers of exercise performance, inflammation and muscle damage were identified (p < 0.05). Acute eccentric resistance exercise is sufficient to induce tissue-specific DNA methylation modifications to TNF and IL6; however, neither eccentric training nor supplementation was sufficient to further modify the DNA methylation.