Time to contraction time ratio (FT:CT) obtained from a countermovement jump (CMJ) on the relationships between yo-yo intermittent recovery (level 2) test (yo-yo IR2), match exercise intensity (high-intensity running [HIR] m·min−1 and Load·min−1) and Australian football (AF) performance. Thirty-seven data sets were collected from 17 different players across 22 elite AF matches. Each data set comprised an athlete's yo-yo IR2 score before the start of the season, match exercise intensity via global positioning system and on-field performance rated by coaches' votes and number of ball disposals. Each data set was categorized as normal (>92% baseline FT:CT, n = 20) or fatigued (<92% baseline FT:CT, n = 17) from a single CMJ performed 96 hours after the previous match. Moderation-mediation analysis was completed with yo-yo IR2 (independent variable), match exercise intensity (mediator), and AF performance (dependent variable) with NMF status as the conditional variable. Isolated interactions between variables were analyzed by Pearson's correlation and effect size statistics. The Yo-yo IR2 score showed an indirect influence on the number of ball disposals via HIR m·min−1 regardless of NMF status (normal FT:CT indirect effect = 0.019, p < 0.1, reduced FT:CT indirect effect = 0.022, p < 0.1). However, the yo-yo IR2 score only influenced coaches' votes via Load·min−1 in the nonfatigued state (normal: FT:CT indirect effect = 0.007, p 0.1). In isolation, NMF status also reduces relationships between yo-yo IR2 and load·min−1, yo-yo IR2 and coaches votes, Load·min−1 and coaches' votes (Δr > 0.1). Routinely testing yo-yo IR2 capacity, NMF via FT:CT and monitoring Load·min−1 in conjunction with HIR m·min−1 as exercise intensity measures in elite AF is recommended....

We examined acute molecular responses in skeletal muscle to divergent exercise stimuli by combining consecutive bouts of resistance and endurance exercise. Eight men [22.9 ± 6.3 yr, body mass of 73.2 ± 4.5 kg, peak O₂ uptake (V̇o_2peak) of 54.0 ± 5.7 ml·kg⁻¹·min⁻¹] were randomly assigned to complete trials consisting of either resistance exercise (8 × 5 leg extension, 80% 1 repetition maximum) followed by a bout of endurance exercise (30 min cycling, 70% V̇o_2peak) or vice versa. Muscle biopsies were obtained from the vastus lateralis at rest, 15 min after each exercise bout, and after 3 h of passive recovery to determine early signaling and mRNA responses. Phosphorylation of Akt and Akt1^Ser473 were elevated 15 min after resistance exercise compared with cycling, with the greatest increase observed when resistance exercise followed cycling (∼55%; P < 0.01). TSC2-mTOR-S6 kinase phosphorylation 15 min after each bout of exercise was similar regardless of the exercise mode. The cumulative effect of combined exercise resulted in disparate mRNA responses. IGF-I mRNA content was reduced when cycling preceded resistance exercise (−42%), whereas muscle ring finger mRNA was elevated when cycling was undertaken after resistance exercise (∼52%; P < 0.05). The hexokinase II mRNA level was higher after resistance cycling (∼45%; P < 0.05) than after cycling-resistance exercise, whereas modest increases in peroxisome proliferator-activated receptor gamma coactivator-1α mRNA did not reveal an order effect. We conclude that acute responses to diverse bouts of contractile activity are modified by the exercise order. Moreover, undertaking divergent exercise in close proximity influences the acute molecular profile and likely exacerbates acute “interference.”

Telomeres are specialized nucleoprotein structures that protect chromosomal ends from degradation. These structures progressively shorten during cellular division and can signal replicative senescence below a critical length. Telomere length is predominantly maintained by the enzyme telomerase. Significant decreases in telomere length and telomerase activity are associated with a host of chronic diseases; conversely their maintenance underpins the optimal function of the adaptive immune system. Habitual physical activity is associated with longer leukocyte telomere length; however, the precise mechanisms are unclear. Potential hypotheses include regulation of telomeric gene transcription and/or microRNAs (miRNAs). We investigated the acute exercise-induced response of telomeric genes and miRNAs in twenty-two healthy males (mean age = 24.1±1.55 years). Participants undertook 30 minutes of treadmill running at 80% of peak oxygen uptake. Blood samples were taken before exercise, immediately post-exercise and 60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA arrays and telomere extension mRNA array. Results were individually validated in white blood cells and sorted T cell lymphocyte subsets using quantitative real-time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells after exercise. Fifty-six miRNAs were also differentially regulated post-exercise (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric repeat binding factor 2, interacting protein (TERF2IP) was identified as a potential binding target for miR-186 and miR-96 and demonstrated concomitant downregulation (P<0.01) at the corresponding time point. Intense cardiorespiratory exercise was sufficient to differentially regulate key telomeric genes and miRNAs in white blood cells. These results may provide a mechanistic insight into telomere homeostasis and improved immune function and physical health.

Physical exercise has proven cardiovascular benefits, yet there is no clear understanding of the related molecular mechanisms leading to this. Here we determined the beneficial epigenetic effects of exercise after sprint interval training, a form of exercise known to improve cardiometabolic health. We quantified genome-wide leukocyte DNA methylation of 12 healthy young (18–24 yr) men before and after 4 wk (thrice weekly) of sprint interval training using the 450K BeadChip (Illumina) and validated gene expression changes in an extra seven subjects. Exercise increased subjects' cardiorespiratory fitness and maximal running performance, and decreased low-density lipoprotein cholesterol concentration in conjunction with genome-wide DNA methylation changes. Notably, many CpG island and gene promoter regions were demethylated after exercise, indicating increased genome-wide transcriptional changes. Among genes with DNA methylation changes, epidermal growth factor ( EGF), a ligand of the epidermal growth factor receptor known to be involved in cardiovascular disease, was demethylated and showed decreased mRNA expression. Additionally, we found that in microRNAs miR-21 and miR-210, gene DNA methylation was altered by exercise causing a cascade effect on the expression of the mature microRNA involved in cardiovascular function. Our findings demonstrate that exercise alters DNA methylation in circulating blood cells in microRNA and protein-coding genes associated with cardiovascular physiology.

Leukocyte telomeres shorten with age, and excessive shortening is associated with age-related cardiometabolic diseases. Exercise training may prevent disease through telomere length maintenance although the optimal amount of exercise that attenuates telomere attrition is unknown. Furthermore, the underlying molecular mechanisms responsible for the enhanced telomere maintenance observed in endurance athletes is poorly understood. We quantified the leukocyte telomere length and analyzed the expression of telomere-regulating genes in endurance athletes and healthy controls (both n = 61), using quantitative PCR. We found endurance athletes have significantly longer (7.1%, 208-416 nt) leukocyte telomeres and upregulated TERT (2.0-fold) and TPP1 (1.3-fold) mRNA expression compared with controls in age-adjusted analysis. The telomere length and telomere-regulating gene expression differences were no longer statistically significant after adjustment for resting heart rate and relative V̇o_{2 max} (all P > 0.05). Resting heart rate emerged as an independent predictor of leukocyte telomere length and TERT and TPP1 mRNA expression in stepwise regression models. To gauge whether volume of exercise was associated with leukocyte telomere length, we divided subjects into running and cycling tertiles (distance covered per week) and found individuals in the middle and highest tertiles had longer telomeres than individuals in the lowest tertile. These data emphasize the importance of cardiorespiratory fitness and exercise training in the prevention of biological aging. They also support the concept that moderate amounts of exercise training protects against biological aging, while higher amounts may not elicit additional benefits.

In this study, we aimed to investigate physiological determinants of endurance performance that best predict 5000-m average run velocity before and after endurance training. Thirty-nine previously untrained participants completed a 5000-m run; a constant velocity test (measuring running economy); and an incremental treadmill test to determine maximal oxygen uptake, final treadmill velocity, and velocity and oxygen uptake at lactate threshold, before and after six weeks of endurance training. Maximal oxygen uptake, final treadmill velocity, and velocity and oxygen uptake at threshold all increased significantly after training (p < 0.05). Average velocity for 5000 m increased significantly (p < 0.05). Running economy was not significantly altered. Correlation analysis revealed final treadmill velocity was most strongly related to 5000-m performance, in both untrained and trained states (r = 0.89, 0.83). Lactate threshold velocity (r = 0.73, 0.76), maximal oxygen uptake (r = 0.55, 0.51) and oxygen uptake at threshold (r = 0.45, 0.45) also showed significant correlations. In contrast, running economy was not significantly related to performance. These results demonstrate that final treadmill velocity in an V˙O_2max test is the single best predictor of 5000-m performance in untrained and trained states. Furthermore, stepwise regression analysis showed that only velocity at lactate threshold significantly improved the accuracy of prediction provided by final treadmill velocity alone.