4-Hydroxybenzoic acid-mediated lifespan extension in Caenorhabditis elegans

Abstract Here in this study, we isolated 4-hydroxybenzoic acid (4-HBA) from Veronica peregrina and elucidated the anti-aging effect of 4-HBA using Caenorhabditis elegans model system. 4-HBA showed potent lifespan extension in C. elegans under normal culture condition. This compound also exhibited significant increase in stress resistance against osmotic, heat, and oxidative stress conditions. In addition, superoxide dismutase and catalase activities were up-regulated by 4-HBA treatment, resulted in reduced intracellular ROS levels. We also investigated the expression levels of SOD-3 and HSP-16.2 using transgenic strains, and both of them were significantly increased by 4-HBA treatment. Further studies on the aging-related factors revealed that 4-HBA may affect reproduction but not body size and pharyngeal pumping of nematodes. Moreover, 4-HBA fed worms showed increased body movements and decreased lipofuscin accumulation compared to control worms, indicating 4-HBA affects age-associated changes in C. elegans. Our mechanistic studies revealed that there was no significant lifespan extension in 4-HBA-treated sir-2.1 and daf-16 null mutants, indicating they are involved in 4-HBA-mediated lifespan regulation. Our findings suggest that 4-HBA treatment confers increased longevity and stress resistance in C. elegans through not only its strong antioxidant capacity, but also SIR-2.1/SIR2-mediated DAF-16/FOXO activation, independent of dietary restriction and insulin/IGF signaling pathway.