Phenolic acid metabolites of polyphenols act as inductors for hormesis in C. elegans

Phenolic acids as metabolites from polyphenols and especially vanilic acid induce the expression of genes involved in hormetic pathways including sirt-2.1 (adult life span), atfs-1 (unfolded protein response, pyk-1 (glycolysis), and ucp-4 (response to cold) as well as reduce the expression of pck-2 (gluconeogenesis) leading to enhanced life span in aged P X 627 nematodes treated with auxin. [Display omitted] •Hormesis of nutrients were studied in a novel invertebrate model of aging.•Phenolic acid metabolites activate hormetic genes and prolongs life- and health-span.•Activation of several pathways may play an important role for anti-aging activities of polyphenols. Aging represents a major risk factors for metabolic diseases, such as diabetes, obesity, or neurodegeneration. Polyphenols and their metabolites, especially simple phenolic acids, gained growing attention as a preventive strategy against age-related, non-communicable diseases, due to their hormetic potential. Using Caenorhabditis elegans (C. elegans) we investigate the effect of protocatechuic, gallic, and vanillic acid on mitochondrial function, health parameters, and the induction of potential hormetic pathways. Lifespan, heat-stress resistance and chemotaxis of C. elegans strain P X 627, a specific model for aging, were assessed in 2-day and 10-day old nematodes. Mitochondrial membrane potential (ΔΨm) and ATP generation were measured. mRNA expression levels of longevity and energy metabolism-related genes were determined using qRT-PCR. All phenolic acids were able to significantly increase the nematodes lifespan, heat-stress resistance and chemotaxis at micromolar concentrations. While ΔΨm was only affected by age, vanillic acid (VA) significantly decreased ATP concentrations in aged nematodes. Longevity pathways, were activated by all phenolic acids, while VA also induced glycolytic activity and response to cold. While life- and health span parameters are positively affected by the investigated phenolic acids, the concentrations applied were unable to affect mitochondrial performance. Therefore we suggest a hormetic mode of action, especially by activation of the sirtuin-pathway.