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Na/K-ATPase Oxidant Amplification Loop Regulates Cellular Senescence

Komal Sodhi, Krithika Srikanthan, Xiaoliang Wang, Perrine Goguet-Rubio, Athar Nawab, Juan R. Sanabria, Zijian XieS,, Joseph I. Shapiro

As Na/K-ATPase oxidant amplification loop (NKAL) has been implicated in several diseases and oxidant injury plays a pivotal role in aging, we examined the effect of NKAL in the molecular pathogenesis of senescence. First, C57BL6 old mice were supplemented with a western diet to induce oxidant injury and pNaKtide was used to antagonize the NKAL. The western diet-induced functional and morphological changes of aging in adipose tissue and heart were ameliorated by pNaKtide. Next, different in vitro models of oxidative stress-induced aging were employed to study the effect of NKAL in human dermal fibroblasts (HDFs). pNaKtide significantly attenuated the expressions of senescence, cellular injury and apoptosis markers. Further stimulation of the NKAL with glucose oxidase augmented cellular senescence whereas treatment with pNaKtide attenuated it. pNaKtide exhibited a significant protective effect against cellular oxidative stress similar to other antioxidants viz, N-Acetyl Cysteine and Vitamin E. Of note, the attenuation of cellular senescence was greater in pNaKtide treated cells than in the antioxidants treated cells. Hence, the overall findings highlight the potential role of NKAL in the progression of aging, which may help in future antiaging therapeutic interventions.