Metabolic Signature of Leukocyte Telomere Length in Elite Male Soccer Players.

Shamma Al-Muraikhy,Najeha Rizwana,Ilhame Diboun,Alexander S Domling,Abdelali Agouni,Francesco Botre,Francesco Donati,Mohamed A Elrayess,Fatima Al-Khelaifi,Maha Sellami

doi:10.3389/fmolb.2021.727144

Abstract

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.

Highlights

Biological aging is associated with changes in the metabolic pathways
Enrichment analysis confirmed an overrepresentation of lysophosolipids, benzoate metabolites and glycine/serine/threonine metabolites with longer Leukocyte telomere length (LTL), and monoacylglycerols, long change fatty acids, polyunsaturated fatty acids and sphingolipids with shorter LTL (Figure 2)
Studies performed in human cell lines and various model organisms, including non-human primates, have revealed several longevity regulatory pathways involved in genome stability, energy metabolism and self-recognition (Riera et al, 2016; Campisi et al, 2019)

Summary

Introduction

Leukocyte telomere length (LTL) is a predictive marker of biological aging; the underlying metabolic pathways remain largely unknown. Short leukocyte telomere length (LTL) has been associated with age (Lindsey et al, 1991; Slagboom et al, 1994; Abdallah et al, 2009; Broer et al, 2013) as well as multiple age-related diseases such as diabetes (Jeanclos et al, 1998; Fitzpatrick et al, 2007; Zhao et al, 2013), cardiovascular disease (Brouilette et al, 2003; Brouilette et al, 2007; Fitzpatrick et al, 2007; Maubaret et al, 2010; Haycock et al, 2014; Rehkopf et al, 2016) and dementia (Martin-Ruiz et al, 2006; Honig et al, 2012). Despite the large number of studies establishing the link between LTL and wellbeing, the molecular pathways underlying these associations are still largely unknown

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