Human serum metabolic profiles are age dependent

Abstract

Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32-81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10(-04) to 7.8 × 10(-42) , α(corr) = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging.

Fig. 1

Heat map of the fold standard deviation changes between ages, and clustering of these changes, over all ages in 1038 women from KORA F4. The heat map shows changes of x-fold standard deviation from the overall mean concentration for each age year in a color-coded way. Green squares represent a decrease, and red squares an increase. Gray boxes represent groups of metabolites with similar changes with number of metabolites in parentheses. Metabolite names in red indicate our set of 13 metabolites. AA, amino acid; AC, acylcarnitines; PC aa, phosphatidylcholinediacyl; PC ae, phosphatidylcholine acyl-alkyl; and lyso PC a, lysophosphatidylcholine acyl.