Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium

Ashley van der Spek, Linda Broer, Harmen H M Draisma, René Pool, Eva Albrecht, Marian Beekman, Massimo Mangino, Mait Raag, Dale R Nyholt, Harish K Dharuri, Veryan Codd, Najaf Amin, Eco J C de Geus, Joris Deelen, Ayse Demirkan, Idil Yet, Krista Fischer, Toomas Haller, Anjali K Henders, Aaron Isaacs & 19 others Sarah E Medland, Grant W Montgomery, Simon P Mooijaart, Konstantin Strauch, H Eka D Suchiman, Anika A M Vaarhorst, Diana van Heemst, Rui Wang-Sattler, John B Whitfield, Gonneke Willemsen, Margaret J Wright, Nicholas G Martin, Nilesh J Samani, Andres Metspalu, P Eline Slagboom, Tim D Spector, D.I. Boomsma, Cornelia M van Duijn, Christian Gieger

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.

Original languageEnglish
Pages (from-to)11623
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 12 Aug 2019

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Metabolomics
Telomere
Homocysteine
Lipid Metabolism
Leukocytes
Phosphatidylcholines
Methionine
Tyrosine
Cardiovascular Diseases
Telomere Shortening
Lysophosphatidylcholines
Serum
Dementia
Mass Spectrometry
Oxidative Stress
Inflammation
Morbidity
Polymerase Chain Reaction
Mortality

Cite this

van der Spek, Ashley ; Broer, Linda ; Draisma, Harmen H M ; Pool, René ; Albrecht, Eva ; Beekman, Marian ; Mangino, Massimo ; Raag, Mait ; Nyholt, Dale R ; Dharuri, Harish K ; Codd, Veryan ; Amin, Najaf ; de Geus, Eco J C ; Deelen, Joris ; Demirkan, Ayse ; Yet, Idil ; Fischer, Krista ; Haller, Toomas ; Henders, Anjali K ; Isaacs, Aaron ; Medland, Sarah E ; Montgomery, Grant W ; Mooijaart, Simon P ; Strauch, Konstantin ; Suchiman, H Eka D ; Vaarhorst, Anika A M ; van Heemst, Diana ; Wang-Sattler, Rui ; Whitfield, John B ; Willemsen, Gonneke ; Wright, Margaret J ; Martin, Nicholas G ; Samani, Nilesh J ; Metspalu, Andres ; Eline Slagboom, P ; Spector, Tim D ; Boomsma, D.I. ; van Duijn, Cornelia M ; Gieger, Christian. / Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length : the ENGAGE consortium. In: Scientific Reports. 2019 ; Vol. 9, No. 1. pp. 11623.
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abstract = "Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.",
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van der Spek, A, Broer, L, Draisma, HHM, Pool, R, Albrecht, E, Beekman, M, Mangino, M, Raag, M, Nyholt, DR, Dharuri, HK, Codd, V, Amin, N, de Geus, EJC, Deelen, J, Demirkan, A, Yet, I, Fischer, K, Haller, T, Henders, AK, Isaacs, A, Medland, SE, Montgomery, GW, Mooijaart, SP, Strauch, K, Suchiman, HED, Vaarhorst, AAM, van Heemst, D, Wang-Sattler, R, Whitfield, JB, Willemsen, G, Wright, MJ, Martin, NG, Samani, NJ, Metspalu, A, Eline Slagboom, P, Spector, TD, Boomsma, DI, van Duijn, CM & Gieger, C 2019, 'Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium' Scientific Reports, vol. 9, no. 1, pp. 11623. https://doi.org/10.1038/s41598-019-47282-6

Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length : the ENGAGE consortium. / van der Spek, Ashley; Broer, Linda; Draisma, Harmen H M; Pool, René; Albrecht, Eva; Beekman, Marian; Mangino, Massimo; Raag, Mait; Nyholt, Dale R; Dharuri, Harish K; Codd, Veryan; Amin, Najaf; de Geus, Eco J C; Deelen, Joris; Demirkan, Ayse; Yet, Idil; Fischer, Krista; Haller, Toomas; Henders, Anjali K; Isaacs, Aaron; Medland, Sarah E; Montgomery, Grant W; Mooijaart, Simon P; Strauch, Konstantin; Suchiman, H Eka D; Vaarhorst, Anika A M; van Heemst, Diana; Wang-Sattler, Rui; Whitfield, John B; Willemsen, Gonneke; Wright, Margaret J; Martin, Nicholas G; Samani, Nilesh J; Metspalu, Andres; Eline Slagboom, P; Spector, Tim D; Boomsma, D.I.; van Duijn, Cornelia M; Gieger, Christian.

In: Scientific Reports, Vol. 9, No. 1, 12.08.2019, p. 11623.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length

T2 - the ENGAGE consortium

AU - van der Spek, Ashley

AU - Broer, Linda

AU - Draisma, Harmen H M

AU - Pool, René

AU - Albrecht, Eva

AU - Beekman, Marian

AU - Mangino, Massimo

AU - Raag, Mait

AU - Nyholt, Dale R

AU - Dharuri, Harish K

AU - Codd, Veryan

AU - Amin, Najaf

AU - de Geus, Eco J C

AU - Deelen, Joris

AU - Demirkan, Ayse

AU - Yet, Idil

AU - Fischer, Krista

AU - Haller, Toomas

AU - Henders, Anjali K

AU - Isaacs, Aaron

AU - Medland, Sarah E

AU - Montgomery, Grant W

AU - Mooijaart, Simon P

AU - Strauch, Konstantin

AU - Suchiman, H Eka D

AU - Vaarhorst, Anika A M

AU - van Heemst, Diana

AU - Wang-Sattler, Rui

AU - Whitfield, John B

AU - Willemsen, Gonneke

AU - Wright, Margaret J

AU - Martin, Nicholas G

AU - Samani, Nilesh J

AU - Metspalu, Andres

AU - Eline Slagboom, P

AU - Spector, Tim D

AU - Boomsma, D.I.

AU - van Duijn, Cornelia M

AU - Gieger, Christian

PY - 2019/8/12

Y1 - 2019/8/12

N2 - Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.

AB - Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.

U2 - 10.1038/s41598-019-47282-6

DO - 10.1038/s41598-019-47282-6

M3 - Article

VL - 9

SP - 11623

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -