Page 4 - A. Aging

[A. Aging-3]

ATM mediated-p53 signaling pathway forms a novel axis for

senescence control

Su Young Hwang¹, Myeong Uk Kuk¹, Jae Won Kim¹, Young Sam Lee²˙³, Hyon E. Choy⁴, Sang Chul Park²˙⁵,
Joon Tae Park¹

¹Division of Life Sciences, Incheon National University, Incheon 22012, Korea, ²Well Aging Research Center, Daegu

Gyeongbuk Institute of Science and Technology, Daegu 42988, Korea, ³Department of New Biology, Daegu
Gyeongbuk Institute of Science and Technology, Daegu 42988, Korea, ⁴Department of Molecular Medicine,
Chonnam National University Medical School, Gwangju 61186, Korea, ⁵The Future Life & Society Research Center,

Chonnam National University, Gwangju 61186, Korea

Previously, we uncovered a novel mechanism in which senescence is controlled by mitochondrial functional recovery

upon Ataxia-telangiectasia mutated (ATM) inhibition. However, it remains elusive how ATM controls signaling
pathways to achieve restorative effect. In this study, we performed microarray and found that p53 pathway was

differentially expressed upon ATM inhibition. We found that ATM inhibition yields senescence amelioration through
p53-dependent manner. The restorative effect was also afforded by direct p53 inhibition. Furthermore, mitochondrial

metabolic reprogramming via p53 inhibition was a prerequisite for senescence amelioration. Taken together, our
data indicated that p53 pathway functions as potential target for ATM-mediated senescence amelioration.