Advancing age is associated with impairments in numerous physiological systems, leading to an increased risk of chronic disease and disability, and reduced healthspan (the period of high functioning healthy life). The plasma metabolome is thought to reflect changes in the activity of physiological systems that influence healthspan. Accordingly, we utilized an LC-MS metabolomics analysis of plasma collected from healthy young and older individuals to characterize global changes in small molecule abundances with age. Using a weighted gene correlation network analysis (WGCNA), similarly expressed metabolites were grouped into modules that were related to indicators of healthspan, including clinically relevant markers of morphology (body mass index, body fat, and lean mass), cardiovascular health (systolic/diastolic blood pressure, endothelial function), renal function (glomerular filtration rate), and maximal aerobic exercise capacity in addition to conventional clinical blood markers (e.g. fasting glucose and lipids). Investigation of metabolic classes represented within each module revealed that amino acid and lipid metabolism as significantly associated with age and indicators of healthspan. Further LC-MS/MS targeted analyses of the same samples were used to identify specific metabolites related to age and indicators of healthspan, including methionine and nitric oxide pathways, fatty acids, and ceramides. Overall, these results demonstrate that plasma metabolomics profiles in general, and amino acid and lipid metabolism in particular, are associated with ageing and indicators of healthspan in healthy adults.

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