STAT1 Drives the Interferon-Like Response and Aging Hallmarks in Progeria.

ABSTRACT: Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disease caused by the mutant lamin-A protein "progerin," features robust sterile inflammation/interferon (IFN)-like response. Targeting inflammation delays cellular and organismal HGPS phenotypes. However, specific mechanisms driving the sterile inflammation/IFN-like response and how this response causes tissue degeneration/loss in HGPS are unknown. We demonstrate that signal transducer and activator of transcription 1 (STAT1) drives the IFN-like response and aging phenotypes in HGPS cellular and mouse models. Calcitriol and baricitinib strongly repress sterile inflammation/IFN-like response, improving hallmarks of progerin-expressing cells such as mitochondrial, autophagy, and proliferation defects. In vivo,

SUBMITTER: Cancado de Faria R 

PROVIDER: S-EPMC12007894 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature