Novel small molecule inhibition of IKK/NF-κB activation reduces markers of senescence and improves healthspan in mouse models of aging.
NEMO
NF-κB
SR12343
aging
senescence
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
01
09
2021
received:
10
12
2020
accepted:
13
09
2021
pubmed:
5
11
2021
medline:
29
3
2022
entrez:
4
11
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 34734460
doi: 10.1111/acel.13486
pmc: PMC8672781
doi:
Substances chimiques
NF-kappa B
0
I-kappa B Kinase
EC 2.7.11.10
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13486Subventions
Organisme : NIA NIH HHS
ID : P01 AG062413
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG056278
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG043376
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG063543
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017242
Pays : United States
Informations de copyright
© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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