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 O(2) uptake (Vo(2peak)) of 54.0 +/- 5.7 ml.kg(-1) x min(-1)] were randomly assigned to complete trials consisting of either resistance exercise (8 x 5 leg extension, 80% 1 repetition maximum) followed by a bout of endurance exercise (30 min cycling, 70% Vo(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 ( approximately 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 ( approximately 52%; P < 0.05). The hexokinase II mRNA level was higher after resistance cycling ( approximately 45%; P < 0.05) than after cycling-resistance exercise, whereas modest increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha 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."

Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners’ and 56 apparently healthy males’ leukocyte telomere length (T/S ratio) using real-time quantitative PCR. The ultra-marathon runners had 11% longer telomeres (T/S ratio) than controls (ultra-marathon runners: T/S ratio = 3.5±0.68, controls: T/S ratio = 3.1±0.41; β = 0.40, SE = 0.10, P = 1.4×10−4) in age-adjusted analysis. The difference remained statistically significant after adjustment for cardiovascular risk factors (P = 2.2×10−4). The magnitude of this association translates into 16.2±0.26 years difference in biological age and approximately 324–648bp difference in leukocyte telomere length between ultra-marathon runners and healthy controls. Neither traditional cardiovascular risk factors nor markers of inflammation/adhesion molecules explained the difference in leukocyte telomere length between ultra-marathon runners and controls. Taken together these data suggest that regular engagement in ultra-endurance aerobic exercise attenuates cellular aging.

The aim of this study was to verify if yo-yo intermittent recovery test (level 2) (yo-yo IR2) score is linked to Australian football (AF) performance through match exercise intensity. Six week prospective study design. Twenty-one data sets were recorded from nine individual players that completed the yo-yo IR2, and played an Australian Football League match in the first five rounds of the 2010 season wearing a global positioning system (GPS) unit. Simple mediation modelling was used to analyse the inter-relationship between yo-yo IR2 score, match exercise intensity and AF performance. Playing position and experience were also incorporated into the model to identify conditional affects. A significant direct relationship was observed between yo-yo IR2 and number of ball disposals (p<0.1) and a significant indirect relationship was observed between yo-yo IR2 and number of ball disposals through distance travelled at high intensity (HIR m min(-1)) (p<0.1). Moderation analysis showed that playing position affected the relationship between of yo-yo IR2 and HIR m min(-1) (p<0.1) and HIR m min(-1) and total ball disposals (p<0.1). Playing experience also significantly affected the relationship between HIR m min(-1) and total ball disposals. This study is the first to identify the effects of yo-yo IR2 on total ball disposals through HIR m min(-1) performed during AF matches, and that playing position and playing experience affect these interactions.

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.

Our study provides the first evidence showing exercise training reprograms the sperm methylome. Whether these DNA methylation changes are inherited to future generations warrants attention.