Gene, microbiome, and anti-aging doping in sport: molecular mechanisms, detection strategies, and implications for sports rehabilitation medicine

Advances in gene transfer have created legitimate opportunities for tissue repair, but the same tools raise the prospect of illicit use to enhance athletic performance ("gene doping"). Evidence that elite athletes harbour a distinctive gut microbiota has raised a parallel concern that microbiome manipulation, including faecal microbiota transplantation (FMT) from high-performing donors, could be used as a form of biological enhancement ("microbiome doping"). A third, related frontier is anti-aging gene therapy (telomerase and Klotho gene delivery and partial cellular reprogramming) which targets the same muscle- and stem-cell-regenerative pathways relevant to injury recovery and has already reached unregulated human self-experimentation. This narrative review summarises the principal gene-doping targets relevant to performance and recovery (erythropoietin, myostatin/activin inhibitors, insulin-like growth factor 1, PPAR-δ/AMPK reprogramming), their delivery vectors, and current detection strategies. It then reviews athlete-associated gut microbiota signatures, notably the lactate-metabolising bacterium Veillonella atypica, and the feasibility and detection challenges of microbiota transplantation, before examining the rationale, targets, and governance challenges of anti-aging gene therapy. Attention is given to the overlap between all three frontiers and legitimate regenerative, microbiota-directed, or aging-biology therapies under investigation for musculoskeletal, metabolic, and gastrointestinal conditions, an overlap that places rehabilitation clinicians in a sensitive position, particularly with older or master athletes; across all three frontiers, the same biological pathways and delivery technologies are simultaneously being developed for legitimate therapeutic use, creating a recurring dual-use dilemma for clinicians and regulators alike. I review safety risks, the regulatory framework administered by the World Anti-Doping Agency (WADA) and its gaps regarding microbiome and longevity interventions, and the practical responsibilities of rehabilitation professionals. I conclude that interdisciplinary collaboration between molecular biologists, microbiome and aging researchers, anti-doping scientists, and clinicians is essential to keep detection methods and clinical governance aligned with the pace of innovation in these three areas, and we outline specific priorities, including clarification of the regulatory status of microbiota transfer and anti-aging gene constructs, strain-level metagenomic monitoring, and biological-age biomarkers, for achieving this alignment.