Metabolomics profiling reveals novel markers for leukocyte telomere length

Jonas Zierer; Gabi Kastenmüller; Karsten Suhre; Christian Gieger; Veryan Codd; Pei-Chien Tsai; Jordana Bell; Annette Peters; Konstantin Strauch; Holger Schulz; Stephan Weidinger; Robert P Mohney; Nilesh J Samani; Tim Spector; Massimo Mangino; Cristina Menni

Metabolomics profiling reveals novel markers for leukocyte telomere length

Jonas Zierer, Gabi Kastenmüller, Karsten Suhre, Christian Gieger, Veryan Codd, Pei-Chien Tsai, Jordana Bell, Annette Peters, Konstantin Strauch, Holger Schulz, Stephan Weidinger, Robert P Mohney, Nilesh J Samani, Tim Spector, Massimo Mangino, Cristina Menni

Twin Research & Genetic Epidemiology

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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.

Original language	English
Pages (from-to)	77-94
Number of pages	18
Journal	Aging
Volume	8
Issue number	1
Publication status	Published - 20 Jan 2016

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http://www.impactaging.com/papers/v8/n1/full/100874.htmlLicence: CC BY

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@article{e3623e304c5d40888f737ba2d1895821,

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.",

author = "Jonas Zierer and Gabi Kastenm{\"u}ller and Karsten Suhre and Christian Gieger and Veryan Codd and Pei-Chien Tsai and Jordana Bell and Annette Peters and Konstantin Strauch and Holger Schulz and Stephan Weidinger and Mohney, {Robert P} and Samani, {Nilesh J} and Tim Spector and Massimo Mangino and Cristina Menni",

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T1 - Metabolomics profiling reveals novel markers for leukocyte telomere length

AU - Zierer, Jonas

AU - Kastenmüller, Gabi

AU - Suhre, Karsten

AU - Gieger, Christian

AU - Codd, Veryan

AU - Tsai, Pei-Chien

AU - Bell, Jordana

AU - Peters, Annette

AU - Strauch, Konstantin

AU - Schulz, Holger

AU - Weidinger, Stephan

AU - Mohney, Robert P

AU - Samani, Nilesh J

AU - Spector, Tim

AU - Mangino, Massimo

AU - Menni, Cristina

PY - 2016/1/20

Y1 - 2016/1/20

N2 - 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.

AB - 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.

M3 - Article

C2 - 26797767

SN - 1945-4589

VL - 8

SP - 77

EP - 94

JO - Aging

JF - Aging

IS - 1

ER -

Metabolomics profiling reveals novel markers for leukocyte telomere length

Abstract

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