Morin enhances healthspan and neuroprotection in Caenorhabditis elegans via mitochondrial stress adaptation

Morin, a dietary flavonoid with antioxidant and metabolic activity, promotes healthy ageing in Caenorhabditis elegans. Morin extended lifespan by ∼18 % and alleviated age-related decline in neuronal integrity, locomotion, learning and memory, and intestinal fat accumulation. Mitochondrial potential was moderately decreased, suggesting mild uncoupler-like activity. Morin downregulated daf-2 and upregulated daf-16, accompanied by enhanced DAF-16::GFP nuclear localization, indicative of IIS/FOXO pathway activation. Gene expression profiling revealed modulation of mitochondrial stress-responsive (atfs-1, fmo-2), antioxidant (gst-4, hsf-1), and lipid metabolism (fat-6, fat-7) genes. Notably, pink-1 and pdr-1 expression increased, whereas morin's neuroprotective effects were abolished in pink-1; pdr-1 mutants, suggesting that its benefits may involve PINK-1/PDR-1-dependent mitophagy or mitochondrial quality control. Collectively, morin enhances stress resilience and mitochondrial homeostasis through IIS/FOXO-associated regulation, supporting its potential as a natural compound that promotes healthspan.