Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity
Liang Yang, Junfeng Shen, Chunhua Liu, Zhonghua Kuang, Yong Tang, Zhengjiang Qian, Min Guan, Yongfeng Yang, Yang Zhan, Nan Li, Xiang Li
Abstract
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. 18 F-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.