TMED11 Conference
Shaping Future Healthcare with Clinical Research and Personalised Prescribing
Join us at the historic Guildhall, Derry-Londonderry for the 11th TMED Conference – a leading international event in translational medicine bringing together clinical researchers, academics, industry partners and healthcare innovators from across the UK and Europe.
Poster 7- DNA Double Stranded Break Sequencing Following High Intensity Exercise
Authors: Aya M. Mohammed and Gareth W. Davison
Affiliations: School of Sport and Exercise Science, Faculty of life and Health Sciences, Ulster University, Belfast BT15 1AP, Northern Ireland
Background/ Introduction: High-intensity exercise (HIE) (>75% V̇O2max) imposes a significant rise in reactive oxygen and nitrogen species (RONS) leading to a state of oxidative stress, with downstream consequences such as DNA damage, including guanine oxidation (GO), single- and double-strand breaks (DSBs). DSBs are the most dangerous type of DNA damage and can be fatal to the cell if not properly repaired (Williamson et al. 2020; Tryfidou et al. 2020b). Interestingly, there is emerging research in exercise-induced global genomic DSBs using several technologies, for instance, γ-H2AX/53BP1 foci and the comet assay (Williamson et al. 2020), have driven new mechanistic insights aligned to the exercise-induced DSB-repair response. However, current evidence does not distinguish whether this damage is randomly distributed or localised to specific genomic regions of functional significance. Moreover, there is no research examining the exercise-induced DNA damage-repair response at the level of defined genomic loci.
Material & Methods: To address the above shortfall, we will perform a double-blinded, randomised, placebo-controlled trial that will recruit 26 active men. Each participant will complete one V̇O2max test and two high-intensity interval exercise (HIIE) trials, including 4 x 4-minute bouts at 90-95% V̇O2max, interspaced with 3 minutes of active recovery at ~70% HRmax (Williamson et al., 2020). Pre- and post-exercise blood samples will be utilised to measure several metabolites indicative of DNA damage and RONS formation. A DNA adduct-omics genome-wide mapping approach will be applied using INDUCEseq (Dobbs et al., 2022) and Illumina Nextseq 2000 sequencing.
Results: A comprehensive mapping of DNA lesions (DSBs) and the identification of genomic loci most vulnerable to oxidative damage
Conclusion: Understanding how our genome can be shaped in response to exercise-induced DNA damage.
