Aryl Hydrocarbon Receptor-Dependent and -Independent Pathways Mediate Curcumin Anti-Aging Effects

Area of Science:

• Aging research
• Molecular biology
• Pharmacology

Background:

• The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by compounds like curcumin.
• Both AhR and curcumin exhibit conserved effects on aging processes.
• Investigating the interplay between AhR and curcumin's anti-aging mechanisms is crucial.

Purpose of the Study:

• To determine if and how the aryl hydrocarbon receptor (AhR) mediates the anti-aging effects of curcumin across different species.
• To elucidate the specific mechanisms, both dependent and independent, by which curcumin exerts its anti-aging properties.
• To explore the role of AhR in curcumin's impact on lifespan and cellular health.

Main Methods:

• Utilized a multidisciplinary approach combining in vivo (Caenorhabditis elegans), in vitro (human endothelial cells), and in silico analyses.
• Investigated curcumin's effects on lifespan, protein aggregation, oxidative stress, and cell migration.
• Examined the involvement of the aryl hydrocarbon receptor (AhR) and the Nrf2/SKN-1 pathway.

Main Results:

• Curcumin demonstrated context-specific AhR-dependent and AhR-independent anti-aging effects.
• In C. elegans, AhR mediated curcumin-induced lifespan extension, potentially via a ligand-independent antioxidant mechanism.
• Curcumin also provided AhR-independent benefits, including protection against protein aggregation and oxidative stress, and enhanced endothelial cell migration, largely through the Nrf2/SKN-1 pathway.

Conclusions:

• Curcumin possesses multifaceted anti-aging properties, acting through both AhR-dependent and AhR-independent pathways.
• The aryl hydrocarbon receptor (AhR) plays a significant role in mediating some of curcumin's lifespan-extending and protective effects.
• AhR-independent mechanisms, particularly involving the Nrf2/SKN-1 pathway, contribute substantially to curcumin's broad anti-aging activities.