The chemically defined herbal mixture ADAPT-232 delays mitochondrial dysfunction and promotes healthspan through mitophagy-related pathways mediated by the DAF-16/NHR-49 axis

BACKGROUND: Mitochondrial dysfunction and metabolic imbalance are major contributors to the progression of age-related disorders, including cardiovascular diseases. Current therapeutic strategies increasingly focus on preserving mitochondrial integrity and promoting healthspan to reduce cardiometabolic burden. The standardized, chemically well-defined adaptogenic combination ADAPT-232 has a long history as a stress-protective remedy, enhancing cognitive and physical resilience. However, its effects on healthspan, particularly mitochondrial function, and the underlying molecular mechanisms remain insufficiently understood. PURPOSE: The current study investigated whether ADAPT-232 can mitigate glucose-induced metabolic and mitochondrial dysfunction in Caenorhabditis elegans and aimed to elucidate the molecular pathways involved in its biological activity. METHODS: Healthspan parameters, including lifespan, stress resistance, and body morphology, were evaluated following ADAPT-232 supplementation. To investigate the protective potential of the formula under metabolic stress, a glucose-induced dysfunction model was employed, analysing mitochondrial morphology and lipid accumulation. Expression of markers of mitophagy, autophagy, metabolic regulation, and stress-response was assessed through RT-qPCR and GFP- reporter strains. RESULTS: The herbal combination ADAPT-232 significantly extended lifespan and enhanced thermal and oxidative stress resistance. In glucose-stressed worms, the formula restored mitochondrial integrity and reduced lipid accumulation. At the molecular level, ADAPT-232 upregulated pink-1, dct-1, and lgg-2, indicating increased mitophagy and autophagic activity. Upregulation of NHR-49, ATGL-1, and lipl-4 supported improved lipid catabolism and metabolic flexibility. The ADAPT-232 reactivated DAF-16 and skn-1, consistent with enhanced stress-response signalling. CONCLUSION: The formula ADAPT-232 alleviates glucose-induced mitochondrial dysfunction by activating mitophagy-related pathways and improving metabolic homeostasis through coordinated regulation involving DAF-16 and NHR-49. These findings position ADAPT-232 as a promising plant-based intervention for promoting healthspan and potentially reducing cardiovascular risk.