Metabolomic markers reveal novel pathways of ageing and early development in human populations

Menni, Cristina and Kastenmüller, Gabriella and Petersen, Ann Kristin and Bell, Jordana T and Psatha, Maria and Tsai, Pei-Chien and Gieger, Christian and Schulz, Holger and Erte, Idil and John, Sally and Brosnan, M Julia and Wilson, Scott G and Tsaprouni, Loukia and Lim, Ee Mun and Stuckey, Bronwyn and Deloukas, Panos and Mohney, Robert and Suhre, Karsten and Spector, Tim D and Valdes, Ana M (2013) Metabolomic markers reveal novel pathways of ageing and early development in human populations. International journal of epidemiology, 42 (4). pp. 1111-1119. ISSN 1464-3685

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Abstract

BACKGROUND

Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age.

METHODS

Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels.

RESULTS

We identified a panel of 22 metabolites which combined are strongly correlated with age (R(2) = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10(-157)) and lung function (FEV1 beta = -0.04, SE = 0.008, P = 1.8 × 10(-8) adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = -0.01, SE = 0.002, P = 1.9 × 10(-6)) and birthweight (beta = -0.06, SE = 0.01, P = 2.5 × 10(-9)). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10(-6)). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = -0.20, SE = 0.04, P = 2.9 × 10(-8)). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes.

CONCLUSIONS

Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing.

Item Type: Article
Subjects: C100 Biology
C400 Genetics
C700 Molecular Biology, Biophysics and Biochemistry
Divisions: UoA Collections > UoA 03: Allied Health Professions, Dentistry, Nursing & Pharmacy
Faculty of Health, Education and Life Sciences > School of Health Sciences
Depositing User: Loukia Tsaprouni
Date Deposited: 17 Jul 2017 08:41
Last Modified: 17 Jul 2017 08:41
URI: http://www.open-access.bcu.ac.uk/id/eprint/4786

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