From epigenetics to anti-doping application: a new tool of detection

Abstract

Eukaryotic genomes transcribe up to 90% of the genomic DNA but only 1-2% of these transcripts encode for proteins, whereas the vast majority are transcribed as non-coding RNAs (ncRNAs). They are divided into short ncRNA, particularly micro-RNA (miRNA) and small interference RNA (siRNA), and long ncRNAs. Noteworthy, they are unexpectedly stable since they are protected from degradation through different mechanisms: package in exosomes/microvesicles structures, in apoptotic bodies, in HDL lipoprotein, or by RNA binding proteins. For several years already, biomarkers have been used to detect biological disease; in the last years, a requirement appeared to find some of them to unearth the signs of doping. The potential of ncRNAs as a biological candidate is strongly debated and it seems to have become the right tool in the anti-doping hands. In the recent years, the next-generation sequencing (NGS) technology was used by the World Anti-Doping Agency to draft the athlete biological passport (ABP), measuring the circulating miRNAs and applying these new biomarkers in anti-doping. NGS technology does not require any prior knowledge of ncRNAs, but the limit to employ this biomarker to detect performanceenhancing drug use must consider the intrinsic and extrinsic factors that might affect measurements.

Physical Activity and Brain Health

“…Some miRNAs, such as miR-124 and miR-134, have been also suggested to be involved in memory formation and maintenance [218,219]. The relationship between the role of these molecules and BDNF in AD is, however, still debated [220].…”

Physical activity, nutrition, and bone health

“…the mechanical stimulus provided by physical exercise seems to directly influence microrNA (mirNA), an abundant class of short non-coding rNA, molecules composed of about 22 nucleotides [23]. MirNA and protein translation are involved in multiple biological processes including cell proliferation, differentiation, survival, transposing silencing [24], and self-renewal of stem cells [25]. MirNA has been shown to play a regulatory role in bone metabolism [26,27], in mesenchymal bone marrow stem cells (bMSC) and in osteoblasts [28], which suggests that mirNAs could be one of the main mechanisms by which exercise or mechanical load regulate bone metabolism and promote bone formation.…”

Extracellular Vesicle‐Associated RNA as a Carrier of Epigenetic Information

“…As mentioned, vesicles contain different types of ncRNAs, such as miRNAs [ 5 , 52 ], lncRNAs [ 6 ], and circRNAs [ 7 ]. Moreover, specific mRNAs can be delivered to recipient cells [ 103 ], and at least sometimes translated in this new location [ 8 , 43 ], generating a functional protein [ 9 ] (see Section 5 ). As we will discuss below, an important point should be to understand whether the loading of RNAs into vesicles is a random mechanism.…”