Acute exercise leads to regulation of Telomere-Associated genes and MicroRNA expression in immune Cells

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. Funding NHMR

Regulation of telomere length and telomerase activity during aging and immortality

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Variations in pre-hospital fibrinolysis process of care: insights from the Assessment of the Safety and Efficacy of a New Thrombolytic 3 Plus international acute myocardial infarction pre-hospital care survey.

Contains fulltext : 59107.pdf (publisher's version ) (Closed access)The Assessment of the Safety and Efficacy of a New Thrombolytic 3 (ASSENT 3 PLUS) Plus trial (n=1639) was an international trial of pre-hospital fibrinolysis with tenecteplase randomly assigned to enoxaparin or unfractionated heparin, involving 106 sites in 12 countries. Given the potential impact of process of care delivery in various healthcare systems, we undertook a comprehensive validated survey of population demographics, geographical factors, emergency medical services, methods of electrocardiogram interpretation and pre-hospital fibrinolysis administration. The potential study population was 42.4 x 10(6) with 70% urban. The land areas of individual emergency medical services sites varied from 6 to 20000/km(2). Three emergency medical services personnel (range 2-5) attended each ambulance with the highest level of training, consisting of a physician (65%), registered nurse (20%) or paramedic. Before the initiation of the study, 72% of sites administered pre-hospital fibrinolysis (range 1-20 years). Electrocardiograms were interpreted on the scene in 60% and transmitted for physician's interpretation in the remainder; 41% of patients (679/1639) were enrolled at sites without a physician at the scene. The ASSENT 3 Plus trial incorporated a wide variation in population density, emergency medical services resources, and physician's interpretation of ECG and administering pre-hospital fibrinolysis. Understanding this diversity will help in evaluating the general applicability and feasibility of pre-hospital fibrinolysis in various health systems, as well as the pre-hospital care of ST elevation myocardial infarction patients regardless of reperfusion strategies