Involvement of Aryl Hydrocarbon Receptor in Longevity and Healthspan: Insights from Humans, Mice, and C. elegans

Int J Mol Sci. 2024 Sep 14;25(18):9943. doi: 10.3390/ijms25189943.

Abstract

In previous studies, using transcriptomic analysis, we observed higher levels of aryl hydrocarbon receptor (AHR) gene expression in the peripheral blood cells of centenarians compared to octogenarians. This suggests the potential significance of this receptor in maintaining physiological balance and promoting healthy aging, possibly linked to its critical role in detoxifying xenobiotics. In our current study, we confirmed that AHR expression is indeed higher in centenarians. We employed C. elegans as a model known for its suitability in longevity studies to explore whether the AHR pathway has a significant impact on lifespan and healthspan. Our survival assays revealed that two different mutants of AHR-1 exhibited lower longevity. Additionally, we used a mouse model to examine whether supplementation with pomegranate extract modulates the expression of AHR pathway genes in the liver. Furthermore, we studied a nutritional strategy based on pomegranate extract administration to investigate its potential modulation of life- and healthspan in worms.

Keywords: aryl hydrocarbon receptor; lifespan; pomegranate extract; vitality.

MeSH terms

  • Aged, 80 and over
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Female
  • Humans
  • Longevity* / drug effects
  • Longevity* / genetics
  • Male
  • Mice
  • Plant Extracts / pharmacology
  • Pomegranate / chemistry
  • Receptors, Aryl Hydrocarbon* / genetics
  • Receptors, Aryl Hydrocarbon* / metabolism

Substances

  • Plant Extracts
  • Receptors, Aryl Hydrocarbon
  • AHR protein, human
  • Ahr protein, mouse
  • ahr-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Basic Helix-Loop-Helix Transcription Factors