Page 8 - A. Aging

[A. Aging-5]

Mitochondrial metabolic reprograming via AKT inhibition

ameliorates senescence

Jaewon Kim¹, Joontae Park¹

¹Division of Life Sciences, Incheon National University, Incheon KS006, Korea

Senescence is a phenomenon characterized by cell division being stopped due to irreversible cell cycle arrest. Recent
studies have revealed that activation of serine / threonine-protein kinases (AKT1, AKT2 and AKT3) mediates various
downstream responses related to cell cycle regulation. However, it is not known whether AKT inhibition can restore

senescent cells. In this study, we treated various AKT inhibitors on senescent cells and found that GDC0068 most

effectively increased cellular proliferation. Moreover, we investigated how AKT inhibition affects mitochondrial
function through flow cytometry. AKT inhibition improved ROS and MMP levels in senescent cells and confirmed
that mitochondrial metabolic reprogramming caused. Furthermore, mitochondrial metabolic reprogramming via

AKT inhibition is an essential process for senescence amelioration. Taken together, our data shown a novel
mechanism that AKT inhibition leads to mitochondrial metabolic reprogramming, which senescence amelioration.