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The Na/K-Atpase Oxidant Amplification Loop Regulates Aging, Komal Sodhi, Alexandra Nichols, Amrita Mallick, Rebecca L. Klug, Jiang Liu, Nader G. Abraham, Joseph I. Shapiro
The Na/K-Atpase Oxidant Amplification Loop Regulates Aging, Komal Sodhi, Alexandra Nichols, Amrita Mallick, Rebecca L. Klug, Jiang Liu, Nader G. Abraham, Joseph I. Shapiro
Nader G. Abraham
As aging involves oxidant injury, we examined the role of the recently described Na/K-ATPase oxidant amplification loop (NKAL). First, C57Bl6 old mice were given a western diet to stimulate oxidant injury or pNaKtide to antagonize the NKAL. The western diet accelerated functional and morphological evidence for aging whereas pNaKtide attenuated these changes. Next, human dermal fibroblasts (HDFs) were exposed to different types of oxidant stress in vitro each of which increased expression of senescence markers, cell-injury, and apoptosis as well as stimulated the NKAL. Further stimulation of the NKAL with ouabain augmented cellular senescence whereas treatment with pNaKtide attenuated it. …