Acute exercise leads to regulation of telomere-associated genes and microRNA expression in immune cells

• Published in: PloS one Vol. 9; no. 4; p. e92088
• Main Authors: Chilton, Warrick L, Marques, Francine Z, West, Jenny, Kannourakis, George, Berzins, Stuart P, O'Brien, Brendan J, Charchar, Fadi J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-04-2014; Public Library of Science (PLoS)
• Subjects: Adaptive systems; Adult; Binding; Biology and Life Sciences; Blood; Blood cells; Blood tests; Cancer; Care and treatment; Cellular structure; Chronic diseases; Chronic illnesses; Cytomegalovirus; Deoxyribonucleic acid; DNA; Epidemiology; Erythrocytes; Exercise; Exercise - physiology; Exercise Test; Family medical history; Fitness equipment; Gene expression; Gene Expression Regulation; Gene regulation; Genes; Genetic aspects; Genome, Human - genetics; Health aspects; Health sciences; Heart rate; Homeostasis; Humans; Immune response; Immune system; Immune System - cytology; Immunology; Infections; Kinases; Leukocytes; Leukocytes - metabolism; Lymphocytes T; Male; Males; Medical research; Medicine and Health Sciences; Metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Oxygen; Oxygen uptake; Physical activity; Physical fitness; Physical training; Physiology; Polymerase Chain Reaction; Reproducibility of Results; Ribonucleic acid; Risk factors; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-directed DNA polymerase; Running; Senescence; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; Telomerase; Telomerase reverse transcriptase; Telomere - genetics; Telomeres; Transcription; White blood cells; Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092088

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.