Broccoli-licorice-passionflower blend improves mitochondrial function and exerts senotherapeutic effects.

UNLABELLED: Aging is driven by multiple interconnected mechanisms, necessitating interventions that target multiple hallmarks of aging. Using a data-driven prioritization strategy, we screened 16 extract combinations generated from four candidate extracts (broccoli, licorice, passionflower, and lemon balm) and identified an optimized formulation, Blend 2, composed of broccoli, licorice, and passionflower extracts. Blend 2 restored mitochondrial respiration, ATP production, and citrate synthase activity under DNA damage-induced mitochondrial dysfunction through activation of the SIRT1-AMPK-PGC-1α pathway and enhanced mitophagy. It also exhibited dual senotherapeutic activity by suppressing the senescence-associated secretory phenotype via NF-κB inhibition and selectively eliminating senescent cells through the Bax/caspase pathway. These findings demonstrate that data-driven formulation strategies can identify multifunctional natural product combinations and establish Blend 2 as a promising candidate for targeting multiple hallmarks of aging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s10068-026-02265-y.