Elite rock climbing is characterized by sustained upper-limb-dominant loading and complex systemic demands. However, the molecular signatures associated with elite climbing-related adaptation remain poorly defined. This study integrates physiological, functional, transcriptomic, and metabolomic profiling to characterize the potential mechanisms underlying these adaptations. This is a cross-sectional study comparing the molecular profiles of elite rock climbers and matched non-climbers. A total of 40 participants were recruited, comprising 20 elite rock climbers certified as National Master Sportsmen (athlete group) and 20 age, sex, and body mass matched non climbers (control group). Participants underwent functional assessments for vascular reactivity via flow-mediated dilation and climbing specific forearm endurance through dead hang and intermittent grip tests. Fasting venous blood samples were analyzed for biochemical markers, while integrated transcriptomic and metabolomic profiles were established to identify molecular signatures. Data were analyzed using differential expression profiling, functional enrichment, and joint pathway analysis, with results validated by qRT-PCR. The athlete group exhibited significantly superior functional performance characterized by enhanced vascular endothelial function and prolonged forearm endurance alongside widespread systemic adaptations, as reflected by elevated levels of cortisol, creatine kinase, blood urea nitrogen, hemoglobin, plasma volume and total hemoglobin mass ( p < 0.05). RNA sequencing identified 850 differentially expressed genes (|log₂FC| ≥ 1, FDR < 0.05), which were predominantly enriched in cAMP, Apelin, PPAR, TNF, and HIF-1 signaling pathways. Metabolomics detected 71 differential metabolites ( VIP ≥ 1, |log₂FC| ≥1.5, FDR < 0.05), enriched in Insulin secretion, glycolysis/gluconeogenesis, fatty acid degradation, and amino acid metabolism. Integrated transcriptomic and metabolomic analyses revealed that elite climbers exhibited multidimensional molecular adaptation signatures associated with the specific demands of climbing, mainly characterized by enhanced metabolic flexibility, vascular regulation, and optimized metabolic homeostasis. These changes collectively optimized metabolic flexibility, redox homeostasis and controlled inflammation. Validation via qRT-PCR confirmed the RNA-Seq results. Elite rock climbers exhibited multilayered physiological, transcriptional, and metabolic features associated with energy homeostasis, redox balance, inflammatory modulation, and neuromuscular performance. These insights establish a molecular blueprint for evidence-based training optimization and personalized sports interventions.
Liang et al. (Fri,) studied this question.