Metabolomic markers reveal novel pathways of ageing and early development in human populations
Open accessAbstract
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.
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State-of-the-art mass spectrometry and NMR methods can identify hundreds to thousands of metabolites in human plasma.
“State-of-the-art mass spectrometry and NMR methods can identify hundreds to thousands of metabolites in human plasma, and multiple studies have attempted to understand how they interact with ageing113–116.”
From Measuring biological age using omics data (2022) · cites this paper as [116]
Metabolomic clocks have demonstrated lower age prediction accuracy than other omics data types despite training on extremely large sample sizes, and effect sizes for ageing traits have been modest.
“Furthermore, metabolomic clocks have demonstrated lower age prediction accuracy than other omics data types despite training on extremely large sample sizes, and effect sizes for ageing traits have been modest113,116–121.”
From Measuring biological age using omics data (2022) · cites this paper as [116]
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- Authors
- Menni, C., Kastenmüller, G., Petersen, A. K., Bell, J. T., Psatha, M., Tsai, P.-C., Gieger, C., Schulz, H., Erte, I., John, S., Brosnan, M. J., Wilson, S. G., Tsaprouni, L., Lim, E. M., Stuckey, B., Deloukas, P., Mohney, R., Suhre, K., Spector, T. D., & Valdes, A. M.
- Affiliations
- University of Nottingham (GB)
- Corresponding author
- Valdes, Ana M
- ORCID
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-06-29
- Volume
- 42
- Issue
- 4
- Pages
- 1111-1119
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- PMC
- PMC3781000
- OpenAlex
- W2109880669
- Cited by
- 282
- References
- 34
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 27 · 2023: 17 · 2022: 23 · 2021: 26 · 2020: 28 · 2019: 20 · 2018: 22 · 2017: 18 · 2016: 25 · 2015: 24 · 2014: 12 · 2013: 5
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- International Journal of Epidemiology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- BCU Open Access Repository (Birmingham City University) (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Wellcome Trust (098051)
- European Commission (277849)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- human aging, metabolomic markers, birth weight, monozygotic twin discordance, DNA methylation, CpG sites, lung function, bone mineral density, early development, epigenetics
- MeSH terms
- Adolescent, Adult, Aged, Aging, Birth Weight, Forced Expiratory Volume, Humans, Middle Aged, Phenotype, Tryptophan, Twins, Monozygotic, Vital Capacity, Biomarkers, Bone Density, DNA Methylation, Metabolomics, Young Adult
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