Association of circulating branched-chain amino acids with cardiometabolic traits differs between adults and the oldest-old

Branched-chain amino acids (BCAAs) are promising for their potential anti-aging effects. However, findings in adults suggest that circulating BCAAs are associated with cardiometabolic risk. Moreover, little information is available about how BCAAs influence clustered cardiometabolic traits in the oldest-old (>85 years), which are the fastest-growing segment of the population in developed countries. Here, we applied a targeted metabolomics approach to measure serum BCAAs in Chinese participants (aged 21-110 years) based on a longevity cohort. The differences of quantitative and dichotomous cardiometabolic traits were compared across BCAAs tertiles. A generalized additive model (GAM) was used to explore the dose-response relationship between BCAAs and the risk of metabolic syndrome (MetS). Overall, BCAAs were correlated with most of the examined cardiometabolic traits. The odds ratios for MetS across the increasing BCAA tertiles were 3.22 (1.70 – 6.12) and 5.27 (2.88 – 9.94, referenced to tertile 1) after adjusting for age and gender (P(trend) < 0.001). The association still existed after further controlling for lifestyle factors and inflammation factors. However, the correlations between circulating BCAAs and quantitative traits were weakened in the oldest-old, except for lipids, the levels of which were distinctly different from those in adults. The stratified analysis also suggested that the risky BCAAs-MetS association was more pronounced in adults than in the oldest-old. Moreover, generalized additive model (GAM)-based curve-fitting suggested that only when BCAAs exceeded a threshold (approximately 450 μmol/L) was the BCAAs-MetS association significant. The relationship might be aging-dependent and was more pronounced in adults than in the oldest-old.