Myricitrin Delays Caenorhabditis elegans Aging: Association with DAF-16, SIR-2.1, and Potential Cholinergic Modulation

Background: Aging involves progressive functional decline driven by oxidative stress and mitochondrial dysfunction(definition), and dietary flavonoids are promising aging interventions due to their multi-target regulatory pathways. Methods: This study systematically evaluated the anti-aging activity of myricitrin (MYR) and its underlying mechanisms using Caenorhabditis elegans, testing MYR at 0.25 mg/mL, employing a rotenone-induced model of mitochondrial oxidative stress, and performing reporter strain analyses, qRT-PCR, and molecular docking analysis with acetylcholinesterases (ACE-1/2). Results: MYR at 0.25 mg/mL significantly extended lifespan and improved locomotor performance without detectable toxicity regarding growth, feeding, or reproduction; reduced reactive oxygen species accumulation and restored antioxidant enzyme activities in the rotenone-induced model; was accompanied by the nuclear translocation of DAF-16 and the upregulation of associated downstream antioxidant genes (sod-3, gst-4); enhanced mitochondrial quality control by upregulating sir-2.1 and modulating genes associated with the mitochondrial unfolded protein response (atfs-1, hsp-6) and mitochondrial dynamics (fzo-1, drp-1); and indicated a favorable interaction between MYR and acetylcholinesterases (ACE-1/2). Conclusions: MYR represents a promising candidate compound for mitigating aging-related phenotypes, with its beneficial effects linked to a DAF-16-associated antioxidant response and SIR-2.1-correlated mitochondrial quality control network.