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Research Paper|Volume 8, Issue 1|pp 77—86

Metabolomics profiling reveals novel markers for leukocyte telomere length

Jonas Zierer1,2, Gabi Kastenmüller1,2, Karsten Suhre2,3, Christian Gieger4,5,6, Veryan Codd7, Pei-Chien Tsai1, Jordana Bell1, Annette Peters5, Konstantin Strauch8, Holger Schulz9,10, Stephan Weidinger11, Robert P. Mohney12, Nilesh J. Samani7,13, Tim Spector1, Massimo Mangino1,14, Cristina Menni1
  • 1Department of Twin Research & Genetic Epidemiology, King's College London, London, UK
  • 2Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany
  • 3Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar
  • 4Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • 5Institute of Epidemiologie II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • 6German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
  • 7Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
  • 8Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
  • 9Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany
  • 10Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Munich, Germany
  • 11Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
  • 12Metabolon, Inc. Durham, NC 27713, USA
  • 13National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK
  • 14National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, UK
* Co-senior author
Received: October 12, 2015Accepted: January 17, 2016Published: January 20, 2016
https://doi.org/10.18632/aging.100874

Copyright: © 2016 Zierer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.