ATM is a key driver of NF-κB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging
Jing Zhao, Lei Zhang, Aiping Lu, Yingchao Han, Debora Colangelo, Christina Bukata, Alex C. Scibetta, Matthew J. Yousefzadeh, Xuesen Li, Aditi U. Gurkar, Sara J. McGowan, Luise Angelini, Ryan O’Kelly, Hongshuai Li, Lana Corbo, Tokio Sano, Heather Nick, Enrico Pola, Smitha P.S. Pilla, Warren Ladiges, Nam Vo, Johnny Huard, Laura J. Niedernhofer, Paul D. Robbins
Abstract
mice with the ATM inhibitor KU-55933 suppressed markers of senescence and SASP. Taken together, these results demonstrate that the ATM kinase is a major mediator of DNA damage-induced, NF-κB-mediated cellular senescence, stem cell dysfunction and aging and thus represents a therapeutic target to slow the progression of aging.
Topics & Concepts
SenescenceDNA damageCell biologyOxidative stressBiologyStem cellTelomereNF-κBERCC1Cancer researchSignal transductionGeneticsDNANucleotide excision repairEndocrinologyTelomeres, Telomerase, and SenescenceNF-κB Signaling PathwaysDNA Repair Mechanisms