Ageing Investigation Using Two-Time-Point Metabolomics Data from KORA and CARLA Studies

Ageing, one of the largest risk factors for many complex diseases, is highly interconnectedto metabolic processes. Investigating the changes in metabolite concentration during ageing amonghealthy individuals offers us unique insights to healthy ageing. We aim to identify ageing-associatedmetabolites that are independent from chronological age to deepen our understanding of thelong-term changes in metabolites upon ageing. Sex-stratified longitudinal analyses were performedusing fasting serum samples of 590 healthy KORA individuals (317 women and 273 men) whoparticipated in both baseline (KORA S4) and seven-year follow-up (KORA F4) studies. Replicationwas conducted using serum samples of 386 healthy CARLA participants (195 women and 191 men)in both baseline (CARLA-0) and four-year follow-up (CARLA-1) studies. Generalized estimationequation models were performed on each metabolite to identify ageing-associated metabolitesafter adjusting for baseline chronological age, body mass index, physical activity, smoking status,alcohol intake and systolic blood pressure. Literature researches were conducted to understandtheir biochemical relevance. Out of 122 metabolites analysed, we identified and replicated five (C18,arginine, ornithine, serine and tyrosine) and four (arginine, ornithine, PC aa C36:3 and PC ae C40:5)significant metabolites in women and men respectively. Arginine decreased, while ornithine increasedin both sexes. These metabolites are involved in several ageing processes: apoptosis, mitochondrialdysfunction, inflammation, lipid metabolism, autophagy and oxidative stress resistance. The studyreveals several significant ageing-associated metabolite changes with two-time-point measurementson healthy individuals. Larger studies are required to confirm our findings.