Metabolite demonstrated to correlate with age

Researchers have identified a novel biomarker of age-related traits – C-glycosyl tryptophan.

Researchers led by Ana Valdes from Kings College London, (London, UK) have conducted an extensive metabolite analysis across 6055 individuals from the UK, to identify a novel biomarker of age and age-associated traits, C-glycosyl tryptophan (C-glyTrp). The research group used LC–MS and GC–MS techniques to correlate metabolite levels to known phenotypic markers of age, such as telomere length, bone mineral density and circulating levels of dehydroepiandrosterone sulfate. Using a non-targeted metabolomic platform, 165 metabolites were demonstrated to correlate with age, and 22 of these, including C-glyTrp, were found to be associated with age.

Fasting serum samples and plasma samples were used in the quantification of metabolites. The 22 associated with age were discovered to increase steadily from below 20 years to over 65 years. Of these 22, C-glyTrp was of particular interest, and therefore the same analyses of C-glyTrp were conducted in a German population to identify consistency. C-glyTrp was confirmed to be associated with many traits of ageing, most notably lung function, bone marrow density and cholesterol levels. It was also associated to a lower birth weight, a trait known to influence health in later years.

Across twins, the C-glyTrp levels demonstrated a low level of heritably, strongly implying the levels of this metabolite is governed by environmental and epigenetic factors. Given this, further analysis of the methylation status of DNA at the three probes with C-glyTrp in twins discovered that one of these probes differed. This probe was mapped to the promoter of the WDR85 gene which encodes a protein involved in dipthamide synthesis, a key protein involved in various cellular pathways including the cell cycle and RNA translation, as well as having an involvement in embryonic development.

While various analytical limitations were still in place, the data have strongly identified C-glyTrp as a novel biomarker for ageing and age-associated traits. The findings highlight potential in the development of blood testing to rapidly identify the general health and speed of ageing, as well as to provide novel treatments for age-related diseases.

Source: Menni C, Kastenmüller G, Peterson A et al. Metabolomic markers reveal novel pathways of ageing and early development in human populations. Int. J. Epidemiol. doi: 10.1093/ije/dyt094 (2013) (Epub ahead of print).