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

Mech Ageing Dev. 2021 Sep:198:111518. doi: 10.1016/j.mad.2021.111518. Epub 2021 Jun 15.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: C. elegans; Hormesis; Metabolites; Mitochondria; PX627; Polyphenols.

MeSH terms

  • Aging* / drug effects
  • Aging* / metabolism
  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Caenorhabditis elegans
  • Chemotaxis / drug effects
  • Chemotaxis / physiology
  • Energy Metabolism / drug effects
  • Energy Metabolism / genetics
  • Flavoring Agents / pharmacology
  • Gallic Acid / pharmacology*
  • Heat-Shock Response / drug effects
  • Hormesis* / drug effects
  • Hormesis* / physiology
  • Hydroxybenzoates / pharmacology*
  • Longevity / drug effects
  • Longevity / genetics
  • Metabolic Networks and Pathways / drug effects
  • Mitochondrial Turnover / drug effects
  • Mitochondrial Turnover / physiology
  • Polyphenols / pharmacology*
  • Vanillic Acid / pharmacology*

Substances

  • Anticarcinogenic Agents
  • Flavoring Agents
  • Hydroxybenzoates
  • Polyphenols
  • protocatechuic acid
  • Gallic Acid
  • Vanillic Acid
  • phenolic acid