Dataset Information

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

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.

SUBMITTER: van der Spek A

PROVIDER: S-EPMC6690953 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

van der Spek Ashley A Broer Linda L Draisma Harmen H M HHM Pool René R Albrecht Eva E Beekman Marian M Mangino Massimo M Raag Mait M Nyholt Dale R DR Dharuri Harish K HK Codd Veryan V Amin Najaf N de Geus Eco J C EJC Deelen Joris J Demirkan Ayse A Yet Idil I Fischer Krista K Haller Toomas T Henders Anjali K AK Isaacs Aaron A Medland Sarah E SE Montgomery Grant W GW Mooijaart Simon P SP Strauch Konstantin K Suchiman H Eka D HED Vaarhorst Anika A M AAM van Heemst Diana D Wang-Sattler Rui R Whitfield John B JB Willemsen Gonneke G Wright Margaret J MJ Martin Nicholas G NG Samani Nilesh J NJ Metspalu Andres A Eline Slagboom P P Spector Tim D TD Boomsma Dorret I DI van Duijn Cornelia M CM Gieger Christian C

Scientific reports 20190812 1

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 de ...[more]

PMID: 31406173

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Project description:Vitamin D deficiency is common among postmenopausal women. Telomere length can be a potential protective mechanism for age-related diseases. The objective of our study is to examine the association of vitamin D supplementation on leukocyte telomere length (LTL) in healthy postmenopausal women with vitamin D deficiency. The study was designed as a placebo-controlled study to investigate the short-term effects of vitamin D supplementation and seasonal changes on vitamin D related parameters, including 25(OH)D, 1,25(OH)2D parathormone (PTH), Vitamin D binding protein (VDBP), vitamin D receptor (VDR), and telomere length in a cohort of postmenopausal women (n = 102). The group was divided as supplementation (n = 52) and placebo groups (n = 50). All parameters were measured before and after treatment. Serum VDBP levels were measured by ELISA method and VDR, GC (VDBP) gene expressions and relative telomere lengths were measured in peripheral blood mononuclear cells (PBMC) using a quantitative real-time PCR method. The results demonstrate that baseline levels were similar between the groups. After vitamin D supplementation 25(OH)D, 1,25(OH)2D, PTH and VDBP levels were changed significantly compared to the placebo group. At the end of the study period, LTL levels were significantly increased in both groups and this change was more prominent in placebo group. The change in GC expression was significant between treatment and placebo groups but VDR expression remained unchanged. Even though the study was designed to solely assess the effects of vitamin D supplementation, LTL was significantly increased in the whole study group in summer months suggesting that LTL levels are affected by sun exposure and seasonal changes rather than supplementation. The study displayed the short-term effect of Vitamin D supplementation on vitamin D, PTH levels, LTL and vitamin D associated gene expressions. The relation between Vitamin D and LTL is not linear and could be confounded by several factors such as the population differences, regional and seasonal changes in sun exposure.

Dataset Information

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

Publications

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

Similar Datasets

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