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.

Telomeres are repetitive tandem DNA sequences that cap chromosomal ends protecting genomic DNA from enzymatic degradation. Telomeres progressively shorten with cellular replication and are therefore assumed to correlate with biological and chronological age. An expanding body of evidence suggests (i) a predictable inverse association between telomere length, aging and age-related diseases and (ii) a positive association between physical activity and telomere length. Both hypotheses have garnered tremendous research attention and broad consensus; however, the evidence for each proposition is inconsistent and equivocal at best. Telomere length does not meet the basic criteria for an aging biomarker and at least 50% of key studies fail to find associations with physical activity. In this review, we address the evidence in support and refutation of the putative associations between telomere length, aging and physical activity. We finish with a brief review of plausible mechanisms and potential future research directions.

Hillmeister, P. 2016. Acute physical exercise and long-term individual shear rate therapy increase telomerase activity in human peripheral blood mononuclear cells. Acta Physiol (Oxf) 220, 251-262.Telomeres are repetitive tandem DNA sequences (TTAGGG) located at chromosomal ends where they protect genomic DNA from enzymatic degradation. Telomeres are scaffolded upon six regulatory proteins, collectively known as the shelterin complex. A state of replicative senescence is triggered when telomeres reach a critically shortened threshold. This senescent state elicits a sequela of oxidative stress and inflammation.1 Telomerase is an RNA-dependent DNA polymerase that reverse transcribes telomeric repeats to chromosomal ends during genome replication, slowing but not preventing eventual telomere erosion. Observational associations between leucocyte telomere length (LTL) and cardiovascular disease (CVD) abound, yet mechanistic clarity is lacking. Accelerated LTL shortening was initially regarded as a consequential epiphenomenon; however, genetic and prospective studies have garnered support for a causal role.Peripheral artery disease (PAD) is a significant health burden typically resulting in restricted lower limb mobility. This functional limitation restricts exercise capacity and the subsequent vascular adaptations from enhanced distal blood flow (increased fluid shear). In Acta physiologica, Zietzer et al.2 investigated acute telomere homeostasis in the context of PAD (Fontane Stage II), in a small cohort of ageing patients. To achieve this, the authors undertook two separate studies. The significant association between LTL and CVD implies a physiological benefit from increased telomerase expression. The maxim 'if some is good, more must be better' seems to be tacitly accepted in popular discourse. However, it remains to be determined whether an acute increase in PBMC telomerase expression represents a positive pro-telomeric adaptation or is an indicator of cellular stress. Low telomerase activity is often inferred by the presence of shortened telomeres; however, it does not reliably correlate with average telomere length.5 Low telomerase activity is independently associated with major CVD risk factors in humans, 6 yet increased telomerase activity, accompanied by shortened telomeres, is paradoxically associated with progression of subclinical coronary atherosclerosis. 7 Acute increases in telomerase activity may indicate a stressed system attempting to stabilize critically shortened telomeres; 6 a hypothesis evidenced in several pathological models. 7The majority of factors that negatively modulate LTL are also established CVD risk factors. 1 Habitual physical activity appears to confer a measure of telomeric protection, with longer LTL routinely reported amongst the physically active. 8 Despite the everincreasing associations between physical activity and telomere length, a clear mechanistic explanation is lacking. A small yet growing number of studies have investigated exercise-induced modulation of shelterin gene...

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