Aryl Hydrocarbon Receptor Signaling in Aging: A Key Modulator of Brain Homeostasis

Aging results from the gradual accumulation of molecular and cellular damage, and it is a risk factor for neurodegenerative disease. The aryl hydrocarbon receptor (AhR) is increasingly recognized as a key in the regulatory molecular mechanisms that drive aging. AhR is a cytoplasmic receptor activated by diverse endogenous and exogenous ligands. It modulates cell proliferation and differentiation in development and the adult brain. Besides, AhR participates in multiple physiological mechanisms that become dysregulated with age, including neuroinflammation, gut dysbiosis, stem cell maintenance, genomic stability, lipid metabolism, and mitochondrial function, contributing to the onset of neurodegeneration. These interconnected physiological processes lead to cumulative damage that ultimately impairs physical and cognitive function in older individuals. Activation of AhR by selective ligands has been shown to dampen neuroinflammatory responses and support cognitive integrity, underscoring its regulatory role in central nervous system (CNS) homeostasis. This review plumbs current evidence on how AhR influences the molecular mechanisms of aging and explores its potential as a therapeutic target to preserve brain health and mitigate age-related neurological decline.