Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE.

Abstract

Senescent cells have been demonstrated to have lower cellular NAD+ levels and are involved in the development of various age-related diseases, including age-related macular degeneration (AMD). Sodium iodate (NaIO3) has been primarily used as an oxidant to establish a model of dry AMD. Results of previous studies have showed that NaIO3 induced retinal tissue senescence in vivo. However, the role of NaIO3 and the mechanism by which it induces retinal pigment epithelium (RPE) senescence remains unknown. In this study, RPE cell senescence was confirmed to be potentially induced by NaIO3. The results showed that the number of senescence-associated-β-galactosidase (SA-β-gal-)-positive cells and the protein levels of p16 and p21 increased after NaIO3 treatment. Additionally, the senescent RPE cells underwent oxidative stress and NAD+ depletion. Furthermore, significant DNA damage and mitochondrial dysfunction were also detected in senescent RPE cells. The antioxidant N-acetylcysteine (NAC) could alleviate cellular senescence only by a minimal degree, whereas supplementation with nicotinamide mononucleotide (NMN) strongly ameliorated RPE senescence through the alleviation of DNA damage and the maintenance of mitochondrial function. The protective effects of NMN were demonstrated to rely on undisturbed Sirt1 signaling. Moreover, both the expression of senescence markers of RPE and subretinal inflammatory cell infiltration were decreased by NMN treatment in vivo. Our results indicate that RPE senescence induced by NaIO3 acquired several key features of AMD. More importantly, NMN may potentially be used to treat RPE senescence and senescence-associated pre-AMD changes by restoring the NAD+ levels in cells and tissues.

• Authors: Chengda Ren, Chengyu Hu, Yan Wu, Tingting Li, Aiqi Zou, Donghui Yu, Tianyi Shen, Wenting Cai, Jing Yu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 5961123 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35898618 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Chengda Ren et al.

Chemical References

• Iodates
• NAD
• Nicotinamide Mononucleotide
• sodium iodate

Topics

• Cellular Senescence
• Humans
• Inflammation (metabolism)
• Iodates
• Macular Degeneration (metabolism)
• NAD (metabolism)
• Nicotinamide Mononucleotide (metabolism, pharmacology)
• Oxidative Stress
• Retinal Pigment Epithelium (metabolism)