title: Acute exercise leads to regulation of telomere-associated genes and microRNA expression in immune cells.
abstract: 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.
authors.affiliation: School of Health Sciences, Federation University Australia, Victoria, Australia.
authors.forename: Warrick L
authors.initials: WL
authors.lastname: Chilton
authors.affiliation: School of Health Sciences, Federation University Australia, Victoria, Australia.
authors.forename: Francine Z
authors.initials: FZ
authors.lastname: Marques
authors.affiliation: Fiona Elsey Cancer Research Institute, Ballarat, Victoria, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: West
authors.affiliation: Fiona Elsey Cancer Research Institute, Ballarat, Victoria, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Kannourakis
authors.affiliation: Fiona Elsey Cancer Research Institute, Ballarat, Victoria, Australia.
authors.forename: Stuart P
authors.initials: SP
authors.lastname: Berzins
authors.affiliation: School of Health Sciences, Federation University Australia, Victoria, Australia.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: O'Brien
authors.affiliation: School of Health Sciences, Federation University Australia, Victoria, Australia.
authors.forename: Fadi J
authors.initials: FJ
authors.lastname: Charchar
mesh_terms: D000328:Adult; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007107:Immune System / Q000166:cytology*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
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