Metabolomic markers reveal novel pathways of ageing and early development in human populations
Open Access
- 29 June 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in International Journal of Epidemiology
- Vol. 42 (4), 1111-1119
- https://doi.org/10.1093/ije/dyt094
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 (R2 = 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.Keywords
This publication has 32 references indexed in Scilit:
- Diphthamide modification on eukaryotic elongation factor 2 is needed to assure fidelity of mRNA translation and mouse developmentProceedings of the National Academy of Sciences of the United States of America, 2012
- Human serum metabolic profiles are age dependentAging Cell, 2012
- Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing PopulationPLoS Genetics, 2012
- Cohort Profile: TwinsUK and Healthy Ageing Twin StudyInternational Journal of Epidemiology, 2012
- The metabolic footprint of aging in miceScientific Reports, 2011
- Sarcopenia: current theories and the potential beneficial effect of creatine application strategiesBiogerontology, 2011
- Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolomeProceedings of the National Academy of Sciences of the United States of America, 2011
- Pseudomonas exotoxin kills Drosophila S2 cells via apoptosisToxicon, 2010
- Recent results: Biomarkers of agingExperimental Gerontology, 2006
- The diagnostic value of serum concentrations of 2-(α-mannopyranosyl)-l-tryptophan for normal renal functionKidney International, 2004