Aryl hydrocarbon receptor blocks aging-induced senescence in the liver and fibroblast cells.

ABSTRACT: Aging impairs organismal homeostasis leading to multiple pathologies. Yet, the mechanisms and molecular intermediates involved are largely unknown. Here, we report that aged aryl hydrocarbon receptor-null mice (AhR-/-) had exacerbated cellular senescence and more liver progenitor cells. Senescence-associated markers β-galactosidase (SA-β-Gal), p16^Ink4a and p21^Cip1 and genes encoding senescence-associated secretory phenotype (SASP) factors TNF and IL1 were overexpressed in aged AhR-/- livers. Chromatin immunoprecipitation showed that AhR binding to those gene promoters repressed their expression, thus adjusting physiological levels in AhR+/+ livers. MCP-2, MMP12 and FGF secreted by senescent cells were overproduced in aged AhR-null livers. Supporti

SUBMITTER: Nacarino-Palma A 

PROVIDER: S-EPMC9186759 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature