Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity.

Abstract

Imbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms.

• Authors: Liang Yang, Junfeng Shen, Chunhua Liu, Zhonghua Kuang, Yong Tang, Zhengjiang Qian, Min Guan, Yongfeng Yang, Yang Zhan, Nan Li, Xiang Li
• Journal: Nature communications (Nat Commun) Vol. 14 Issue 1 Pg. 900 (02 17 2023) ISSN: 2041-1723 [Electronic] England
• PMID: 36797299 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Cytokines
• NAD
• Nicotine
• nicotinamide phosphoribosyltransferase, mouse

Topics

• Animals
• Male
• Mice
• Aging
• Cytokines (metabolism)
• Energy Metabolism
• Homeostasis
• NAD (metabolism)
• Nicotine