Decoding aging clocks from a metabolomic perspective

Biological age quantifies functional decline beyond chronological aging; however, current epigenetic clocks exhibit limitations in resolving dynamic metabolic fluctuations and tissue-specific aging trajectories. Metabolomics emerges as a pivotal solution, representing the endpoint cascade of biological events shaped by multifactorial interactions that capture real-time physiological status. This review delineates aging clocks through a metabolomic lens and proposes an executable research workflow comprising data preprocessing, feature selection, model construction, and model application. Furthermore, we design a three-phase causal strategy structured as global screening, local verification, and dynamic validation. This integrated methodology aims to enhance the predictive accuracy of aging clocks while strengthening the biological plausibility and causal inference potential of metabolite-derived aging biomarkers. Additionally, we evaluate the translational prospects and applied value of metabolomic aging clocks, providing actionable guidance for extending human healthspan and advancing prevention and treatment strategies for aging-related pathologies.