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 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 C. Ladiges; Nam Vo; Johnny Huard; Laura J. Niedernhofer; Paul D. Robbins

doi:doi:10.18632/aging.102863

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Priority Research Paper Volume 12, Issue 6 pp 4688—4710

ATM is a key driver of NF-κB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging

Figure 4. Genetic reduction of Atm attenuates aging phenotypes and reduces cellular senescence in vivo. (A) Representative images (left panel) of 15-week-old Ercc1^-/Δ and Ercc1^-/ΔAtm^+/- mice illustrating the severity of their dystonia. (B) The composite score of aging symptoms (right panel) was plotted at the indicated ages. n=8-10 mice per group. (C) qRT-PCR analysis of mRNA expression in liver from 12-week-old WT, Atm^+/-, Ercc1^-/Δ and Ercc1^-/ΔAtm^+/- mice. n=3-6 per group. (D) qRT-PCR analysis of mRNA expression in quadriceps from 12-week-old WT, Atm^+/-, Ercc1^-/Δ and Ercc1^-/ΔAtm^+/- mice. n=3-11 per group. (E) qRT-PCR analysis of mRNA expression in liver from 10 to 12-week-old WT, p65^+/-, Ercc1^-/Δ and Ercc1^-/Δp65^+/- mice. n=4-5 per group. (F) mRNA expression of senescence markers in the liver of 12-week-old Ercc1^-/Δ mice treated with 10 mg/kg of KU-55933 intraperitoneally 3 times per week for two weeks. n = 3 per group. Graphs represent mean+/- s.e.m. P value was determined using Student’s t-test. *p<0.05, **p<0.01, ***p <0.001, ****p <0.0001.