Ahr-bacterial diet interaction modulates aging and associated pathologies inC. elegans

Abstract

Genetic and environmental factors concurrently shape the aging process. The nematode Caenorhabditis elegans has been instrumental in the past 30 years to identify most factors and pathways nowadays known to modulate aging. The aryl-hydrocarbon-receptor (AhR) is a transcription factor originally discovered as a dioxin-binding protein and involved in the metabolism of different environmental toxicants and xenobiotics. Since its discovery, the variety of pathophysiological processes regulated by the AhR has grown and previously we disclosed it promotes aging phenotypes across species. Here, we followed up on our previous study and show that lack of C. elegans AHR-1 differentially affects health and lifespan in a context-dependent manner. Notably, we identified a critical role for AhRbacterial diet interaction in animal lifespan, stress resistance, and age-associated pathologies, and narrowed down the dietary factor involved in the observed AhR-dependent features to a bacteria extruded product, likely derived from tryptophan metabolism.

SIRT6 regulates Tryptophan catabolism preventing metabolite imbalance and neurodegeneration

“…An interesting TF that is regulated by tryptophan catabolites is AhR, which directly binds and translocate to the nucleus in response to metabolites such as L-kynurenine and kynurenic acid 17 . AhR affect several pathways in the brain, including neurodegeneration, brain development, sleep patterns and in ammation [17][18][19][20][23][24][25][62][63][64][65] . AhR, when activated by tryptophan metabolites such as L-kynurenine and kynurenic acid, can translocate to the nucleus and affect and affect its target genes 17 .…”

“…AhR been implicated in developmental, protective, and degenerative pathways in the brain 19,21,22 . Exposure to an AhR ligand promotes neurodegenerative disease-like changes in zebra sh 23 , and microbiota byproducts that interact with AhR modulate aging in C. elegans 24 . Moreover, the levels of AhR in the hippocampus and the serum of patients with AD are elevated compared to young or elderly individuals without dementia 25 .…”

The Role of AhR in the Hallmarks of Brain Aging: Friend and Foe

“…For example, exposure to benzo(a)pyrene, an AhR ligand, promotes neurodegenerative disease-like syndromes in zebrafish [16]. Dietary factors, as well as microbiota by-products, that interact with AhR also modulate aging in C. elegans [17], indicating that AhR modulates aging in vertebrate and invertebrate species. Cellular development is also tightly linked with aging [18,19].…”