title: Metabolomics profiling reveals novel markers for leukocyte telomere length.
abstract: Leukocyte telomere length (LTL) is considered one of the most predictive markers of biological aging. The aim of this study was to identify novel pathways regulating LTL using a metabolomics approach. To this end, we tested associations between 280 blood metabolites and LTL in 3511 females from TwinsUK and replicated our results in the KORA cohort. We furthermore tested significant metabolites for associations with several aging-related phenotypes, gene expression markers and epigenetic markers to investigate potential underlying pathways. Five metabolites were associated with LTL: Two lysolipids, 1-stearoylglycerophosphoinositol (P=1.6×10(-5)) and 1-palmitoylglycerophosphoinositol (P=1.6×10(-5)), were found to be negatively associated with LTL and positively associated with phospholipase A2 expression levels suggesting an involvement of fatty acid metabolism and particularly membrane composition in biological aging. Moreover, two gamma-glutamyl amino acids, gamma-glutamyltyrosine (P=2.5×10(-6)) and gamma-glutamylphenylalanine (P=1.7×10(-5)), were negatively correlated with LTL. Both are products of the glutathione cycle and markers for increased oxidative stress. Metabolites were also correlated with functional measures of aging, i.e. higher blood pressure and HDL cholesterol levels and poorer lung, liver and kidney function. Our results suggest an involvement of altered fatty acid metabolism and increased oxidative stress in human biological aging, reflected by LTL and age-related phenotypes of vital organ systems.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.|Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Zierer
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.|Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.|Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|Institute of Epidemiologie II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
authors.forename: Veryan
authors.initials: V
authors.lastname: Codd
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Jordana
authors.initials: J
authors.lastname: Bell
authors.affiliation: Institute of Epidemiologie II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany.|Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.affiliation: Metabolon, Inc., Durham, NC 27713, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mohney
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.|National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Spector
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.|National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005858:Germany; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D018384:Oxidative Stress; D010641:Phenotype; D012042:Registries; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D014427:Twins / Q000235:genetics; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D005227:Fatty Acids
keywords: biological aging; glutathione; metabolomics; oxidative stress; telomere length