Analysis of over 1,400 metabolites in 213 centenarians from the New England Centenarian Study reveals a distinct metabolic fingerprint of extreme longevity. Centenarians showed significantly elevated levels of primary and secondary bile acids, particularly chenodeoxycholic acid (CDCA) and lithocholic acid (LCA), alongside reduced biliverdin and bilirubin levels compared to their offspring and age-matched controls. Crucially, higher bile acid and steroid concentrations correlated with reduced mortality risk.
This metabolomic signature suggests bile acid metabolism may be a previously underappreciated longevity pathway. Bile acids, traditionally viewed as digestive compounds, are now recognized as signaling molecules that regulate glucose homeostasis, inflammation, and cellular stress responses—all critical aging processes. The inverse relationships between survival-associated metabolites and NAD+ production ratios, gut bacterial metabolites, and oxidative stress markers point to interconnected metabolic networks underlying exceptional longevity. The study's development of a metabolomic biological age clock, where deviations predicted mortality independent of chronological age, offers a more precise aging biomarker than conventional approaches. While observational, these findings identify specific metabolic targets that could inform interventions aimed at promoting metabolic resilience in aging populations.
