Myricitrin Delays <i>Caenorhabditis elegans</i> Aging: Association with DAF-16, SIR-2.1, and Potential Cholinergic Modulation.

<h4>Background</h4>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.<h4>Methods</h4>This study systematically evaluated the anti-aging activity of myricitrin (MYR) and its underlying mechanisms using <i>Caenorhabditis elegans</i>, 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).<h4>Results</h4>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 (<i>sod-3</i>, <i>gst-4</i>); enhanced mitochondrial quality control by upregulating <i>sir-2.1</i> and modulating genes associated with the mitochondrial unfolded protein response (<i>atfs-1</i>, <i>hsp-6</i>) and mitochondrial dynamics (<i>fzo-1</i>, <i>drp-1</i>); and indicated a favorable interaction between MYR and acetylcholinesterases (ACE-1/2).<h4>Conclusions</h4>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.