Metabolic Signature of Leukocyte Telomere Length in Elite Male Soccer Players

Introduction: Biological aging is associated with changes in the metabolic pathways. Leukocyte telomere length (LTL) is a predictive marker of biological aging; however, the underlying metabolic pathways remain largely unknown. The aim of this study was to investigate the metabolic alterations and identify the metabolic predictors of LTL in elite male soccer players. Methods: Levels of 837 blood metabolites and LTL were measured in 126 young elite male soccer players who tested negative for doping abuse at anti-doping laboratory in Italy. Multivariate analysis using orthogonal partial least squares (OPLS), univariate linear models and enrichment analyses were conducted to identify metabolites and metabolic pathways associated with LTL. Generalized linear model followed by receiver operating characteristic (ROC) analysis were conducted to identify top metabolites predictive of LTL. Results: Sixty-seven metabolites and seven metabolic pathways showed significant associations with LTL. Among enriched pathways, lysophospholipids, benzoate metabolites, and glycine/serine/threonine metabolites were elevated with longer LTL. Conversely, monoacylglycerols, sphingolipid metabolites, long chain fatty acids and polyunsaturated fatty acids were enriched with shorter telomeres. ROC analysis revealed eight metabolites that best predict LTL, including glutamine, N-acetylglutamine, xanthine, beta-sitosterol, N2-acetyllysine, stearoyl-arachidonoyl-glycerol (18:0/20:4), N-acetylserine and 3-7-dimethylurate with AUC of 0.75 (0.64–0.87, p < 0.0001). Conclusion: This study characterized the metabolic activity in relation to telomere length in elite soccer players. Investigating the functional relevance of these associations could provide a better understanding of exercise physiology and pathophysiology of elite athletes.