Background: Aging is a complex process that results from metabolic activities such as those that generate reactive oxygen species. Metabolomic profiling, an emerging technology, may shed light on metabolites associated with aging and identify key changes associated with premature aging.
Methods: A total of 370 metabolites were profiled using liquid chromatography tandem mass spectroscopy (LC-MS) in plasma from 1153 healthy, control subjects in the Women’s Health Initiative. Metabolite levels were log-transformed and standardized, and each considered individually in statistical models. Linear regression models were created with the metabolite as the outcome and age as the primary exposure: <60 (referent), 60-<65, 65-<70, 70-<75, and 75 years and older. Models were adjusted for matching factors in the primary study (race, time period, hysterectomy status, and then additionally for body mass index, medications (antihypertensives, anti-diabetic drugs, aspirin and statins), and creatinine. The likelihood ratio test was used to compare models with age to model without age, with adjustment for false discovery rate (FDR). Significant results were defined as FDR adjusted p<0.05.
Results: The median age of the women was 68 years (interquartile range 62-72). After multivariate adjustment, thirty-nine metabolites were significantly associated with age >75, including 12 acylcarnitines, 11 free fatty acids, 9 fatty acid derivatives, 2 amino acids, and 5 additional metabolites. Of these, octadecenoyl-L-carnitine (C18:1) had the strongest age association, with levels 0.70 SD (95% CI: 0.48-0.92) higher on average among women >75 years compared to women <60 years of age (referent). C22:0 sphingomyelin (SM), threonine and C24:0 SM were negatively associate with age; levels of these metabolites were on average 0.41 to 0.44 SD lower among the women 75 years and older when compared to the youngest women (linear trend FDR-p value <0.05 for all of these metabolites).
Conclusions: Multiple metabolites involved in mitochondrial fatty acid oxidation, as well as several associated with insulin resistance, have a strong relationship with age, even after adjusting for multiple age-associated factors.