Introduction: Aging represents one of the major risk factors for metabolic diseases, such as diabetes and obesity, or neurodegeneration. Polyphenols and its metabolites, especially simple phenolic acids, have gained more and more attention as a preventive strategy for age-related, non-communicable diseases, due to their hormetic potential. Using the nematode Caenorhabditis elegans (C. elegans) we investigate the effect of protocatechuic, gallic and vanillic acid to improve mitochondrial function and health associated parameters as a preventive measure.Methods: Lifespan, heat-stress resistance and chemotaxis of C. elegans strain PX627, as a specific model for aging, were assessed in 2-day and 10-day old nematodes. Mitochondrial membrane potential (ΔΨm) and ATP generation of young and aged nematodes were measured. mRNA expression levels of longevity and energy metabolism-related genes were determined using qRT-PCR.Results: All phenolic acids were able to significantly increase the nematodes lifespan, heatstress resistance and chemotaxis at micromolar concentrations. While ΔΨm was only affected by age, vanillic acid significantly decreased ATP concentrations in aged nematodes. Genetic analysis revealed increased glycolytic activity mediated through vanillic acid, suggesting improved thermogenesis.
Conclusion:While life-and health-span parameters are positively affected by the investigated phenolic acids, the concentrations applied were unable to impact mitochondrial performance, suggesting hormesis. In contrast to the other phenolic acids, vanillic acid showed potential in regulating glucose homeostasis, making it a prime candidate for future diabetes and obesity focused approaches.