Synergistic effects of 3-O-methylquercetin and polyphenols on longevity, healthspan, and neuroprotection via FOXO/Nrf2.

Péterson Alves Santos, Pricila Pflüger, Juliana Bonnes Bielavski, Gabriel Osório Varriento, Marilise Brittes Rott, Ionara Rodrigues Siqueira, Patrícia Pereira

Laboratory of Neuropharmacology and Preclinical Toxicology, Institute of Basic Health Sciences, Federal University of Rio Grande Do Sul, Porto Alegre, 90050-170, Brazil. · pubmed

Paper

Abstract

Polyphenols are emerging as promising candidates for promoting healthy aging and neuroprotection. Here, we investigated the effects of quercetin (Q), luteolin (L), and 3-O-methylquercetin (3OMQ), individually and in combination (FORM), on lifespan, healthspan, and neurobehavioral functions in Caenorhabditis elegans. Wild-type and mutant strains (including daf-2, daf-16, and skn-1) were exposed to the compounds, followed by assessments of longevity, motility, senescence biomarkers (lipofuscin and red autofluorescence), and neuroprotection against PTZ- and methylmercury-induced damage. 3OMQ and FORM significantly extended lifespan (+ 20-24%) and improved motility and stress resilience, with effects dependent on the DAF-16/FOXO and SKN-1/Nrf2 pathways, but independent of DAF-2/IGF1R signalling. Both compounds induced DAF-16 nuclear translocation and upregulated SKN-1 expression. Furthermore, they attenuated neurodegeneration and cholinesterase hyperactivity following manganese and methylmercury exposure. These findings support the potential of 3OMQ and its polyphenol combination as anti-aging and neuroprotective agents, acting through conserved longevity and oxidative stress pathways.

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Research summary

The paper claims that 3-O-methylquercetin and its polyphenol combination can extend lifespan and improve healthspan in C. elegans through specific longevity pathways. The research investigates mechanisms that could contribute to aging and longevity, focusing on pathways that are directly involved in the aging process rather than merely addressing age-related diseases.

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