Anabolic Androgenic Steroid doping in Weightlifting and the Summer Olympic Games alongside their impact on muscle memory and the human transcriptome

Abstract

Anabolic Androgenic Steroid (AAS) doping pervasiveness, identified retrospectively through International Olympic Committee (IOC) re-tests of the 2004-2012 summer Olympic Games (OG) threatened weightlifting’s place at the 2024 OG. Despite this, analysing doping practices in weightlifting and an investigation of IOC re-test efficacy, across all summer OG sports, is outstanding. AAS induce human hypertrophy via increasing myonuclei, and mice data suggests myonuclei permanency causing a “memory” of exposure and long-term advantage. However, limited human data exists on past AAS users and there is no longitudinal data post AAS exposure. Furthermore, RNA-Seq has yet to be conducted on human samples exposed to AAS. Chapter 1 outlines an introduction and Chapter 2 methodologies. Chapter 3 provides results of analysing weightlifting doping practices from 2008-2019 and identified continental differences in detected substances. Chapter 4 analysed doping that impacted medal results for the 1968-2012 summer OG and showed most doping (74% of medals impacted by doping) was identified retrospectively, either from events prior to OG (17%) or IOC re-tests of 2004-2012 (57%). Chapter 5 describes the males recruited for cross-sectional observational research on AAS and myonuclear permanency and Chapter 6 their transcriptome data. Fifty-six men aged 20-42 years were recruited: Non–resistance trained (C), resistance-trained (RT), RT currently using AAS (RT-AS), of which if AAS usage ceased for ≥18 weeks resampled as Returning Participants (RP) or RT previously using AAS (PREV). There were no significant differences between C (n = 5), RT (n = 15), RT-AS (n = 17), and PREV (n = 6) for trapezius myonuclei per fibre data. Three of 5 returning participants (RP1-3) were sampled longitudinally. Fibre cross-sectional area decreased for RP1 and RP2 between visits, whilst myonuclei per fibre remained similar, congruent with the memory mechanism. However, these values increased for RP3 and self-declared AAS regimens varied. For RNA-Seq, RT-AS was divided to participants who ceased exposure ≤2 or ≥10 weeks prior to sampling. For validation, RNA-Seq was conducted twice but cross comparison of whole blood datasets showed no differential expression between RP time points or comparisons of RT-AS≤2 to other groups. In both muscle datasets, nine differentially expressed genes overlapped with RT-AS≤2 vs RT and RT-AS≤2 vs C, but were not differentially expressed with RT vs C, possibly suggesting they are from acute doping alone, but differential training routines is a confounder. This thesis identified geographical differences in weightlifting doping, demonstrated retrospective doping testing efficacy and contributed data on AAS regarding muscle memory and the human transcriptome.

Date of Award	Jun 2023
Original language	English
Awarding Institution	University of Brighton
Supervisor	Fergus Guppy (Supervisor), Guan Wang (Supervisor) & Yannis Pitsiladis (Supervisor)