Early research suggests the Na/K-ATPase oxidant amplification loop (NKAL), a feed-forward amplification loop for oxidants, plays a critical role in the aging process and eventual oxidant injury, while a newly developed synthetic peptide appears to attenuate cellular senescence, according to findings published June 26, 2018, in Scientific Reports.
Senescence, or cell arrest, and apoptosis cause the phenotypic progressive age-related decline. Oxidant stress is at the forefront of the aging process, causing injury to cellular proteins and DNA, according to the paper.
“When reactive oxygen species (ROS) accumulation exceeds the detoxifying ability of the cell, the resulting oxidative stress induces damage, senescence and apoptosis,” the authors write.
NKAL, the authors of this study have shown, is a non-specific reactive oxygen receptor. It helps to start a signaling cascade for reactive oxygen species generation. The same group developed the pNaKtide peptide from the N domain of the Na/K-ATPase α1 subunit, which inhibits the Na/K-ATPase feed forward amplification of reactive oxygen species, according to the paper.
“I believe our research has delineated a novel mechanism operant in the aging process within cells and, if validated, presents several molecular targets in the aging process,” Joseph I. Shapiro, M.D., senior author and dean of the Marshall University Joan C. Edwards School of Medicine, writes in an email to The Aesthetic Channel. “In particular, we think that the peptide, pNaKtide, that we studied in the paper could have the potential to do this and serve as an ‘anti-aging’ medication. However, we caution the reader that a lot of additional work will be necessary prior to clinical testing of pNaKtide.”
The researchers studied aging mice, feeding the animals a Western diet to stimulate NAKL or pNaKtide to antagonize the NKAL. The Western diet accelerated functional and morphological evidence for aging, whereas pNaKtide attenuated these changes.
They then studied human dermal fibroblasts, which they exposed to different oxidant stressors in vitro. Each of the stressors increased senescence marker expression, cell-injury and apoptosis. The stressors also stimulated NKAL; pNaKtide treatment attenuated cellular senescence. N-Acetyl Cysteine and vitamin E lessened overall oxidant stress to a similar degree as pNaKtide, but pNaKtide protected against senescence more than either antioxidant.
“In particular, pNaKtide appeared to specifically ameliorate nuclear oxidant stress to a greater degree,” the authors write.
Study author Dr. Zijian Xie, Ph.D., discovered the scaffolding function of Na/K-ATPase. The group of authors described NKAL. And pNaKtide was discovered and patented by study authors Drs. Xie and Shapiro.
Sodhi K, Nichols A, Mallick A, et al. The Na/K-ATPase Oxidant Amplification Loop Regulates Aging. Sci Rep. 2018 Jun 26;8(1):9721. doi: 10.1038/s41598-018-26768-9.