Novel small molecule inhibition of IKK/NF-κB activation reduces markers of senescence and improves healthspan in mouse models of aging.

ABSTRACT: Constitutive NF-κB activation is associated with cellular senescence and stem cell dysfunction and rare variants in NF-κB family members are enriched in centenarians. We recently identified a novel small molecule (SR12343) that inhibits IKK/NF-κB activation by disrupting the association between IKKβ and NEMO. Here we investigated the therapeutic effects of SR12343 on senescence and aging in three different mouse models. SR12343 reduced senescence-associated beta-galactosidase (SA-β-gal) activity in oxidative stress-induced senescent mouse embryonic fibroblasts as well as in etoposide-induced senescent human IMR90 cells. Chronic administration of SR12343 to the Ercc1^-/∆ and Zmpste24^-/- mouse models of accelerated aging reduced markers of cellular senescence

SUBMITTER: Zhang L 

PROVIDER: S-EPMC8672781 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature