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Metabolic Features and Pathways Associated With Age-Related Diseases
A precise metabolomics method reveals perturbations in various metabolic pathways are associated with age-related diseases.

A team of researchers led by Dr. Shui Guangshou from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences looked into plasma metabolic features associated with human ageing and revealed perturbations in a diverse array of metabolic pathways across ageing.

Ageing not only causes differences in our appearances but also in our bodily functions. Over time, our organs’ functions decline and metabolism changes. With this comes an increased susceptibility to a variety of diseases. Changes in blood metabolome during ageing can reveal gerontological markers and uncover underlying mechanisms that increase our vulnerability to ageing-related diseases.

Presently, liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) is the most frequently applied analytical platform for metabolome profiling in biomedical research. However, there are still technical issues concerning the accurate identification and quantification of metabolites, especially the analysis of plasma metabolome due to its complicated matrix that often leads to missing or incorrect interpretation of metabolomics data.

In this study, the team first constructed a precise metabolomics method by introducing a series of metabolite isotope standards (ISs), highly covering major classes of plasma endogenous metabolome, to fine-tune the mass spectrometry data of identified metabolites to overcome signal fluctuations of instrument detector and interferences of matrix effects. This introduction of ISs for quantification reduced the coefficients of variations (COVs) of 480 identified metabolites in quality control samples by 4.5 per cent.

Furthermore, the function of these ISs was extended to assist in the identification of unknown metabolites. This was done according to the similar mass spectrometry signal fluctuations and adjacent retention time between the unknown metabolites and ISs across the detection of the entire batch samples, following the principles that they share similar chemical classes, structure, functional groups, and adjacent molecular weights.

Finally, the precise metabolomics approach revealed that plasma metabolome changes across ageing in humans with ages ranging from 20 to 88 years old. It showed that many ageing-associated metabolic pathways like disturbed amino acids metabolism, lipid metabolism, and steroid metabolism were associated with cardiovascular diseases. The results of these findings could provide clues and guidance on the prevention and treatment of these age-related diseases.

Source: Tian et al. (2022). Precise Metabolomics Reveals a Diversity of Aging Associated Metabolic Features.Small Methods, 2200130.

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