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

Author

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  • Liang Yang

    (Chinese Academy of Sciences
    Brain Cognition and Brain Disease Institute (BCBDI)
    Guangdong Provincial Key Laboratory of Brain Connectome, Shenzhen Key Laboratory of Viral Vectors for Biomedicine)

  • Junfeng Shen

    (Chinese Academy of Sciences
    Shenzhen Institute of Synthetic Biology)

  • Chunhua Liu

    (Chinese Academy of Sciences
    Brain Cognition and Brain Disease Institute (BCBDI)
    Guangdong Provincial Key Laboratory of Brain Connectome, Shenzhen Key Laboratory of Viral Vectors for Biomedicine)

  • Zhonghua Kuang

    (Chinese Academy of Sciences
    Institute of Biomedical and Health Engineering
    Paul C. Lauterbur Research Center for Biomedical Imaging)

  • Yong Tang

    (Chinese Academy of Sciences
    Brain Cognition and Brain Disease Institute (BCBDI))

  • Zhengjiang Qian

    (Chinese Academy of Sciences
    Brain Cognition and Brain Disease Institute (BCBDI))

  • Min Guan

    (Chinese Academy of Sciences
    Institute of Biomedicine and Biotechnology)

  • Yongfeng Yang

    (Chinese Academy of Sciences
    Institute of Biomedical and Health Engineering
    Paul C. Lauterbur Research Center for Biomedical Imaging)

  • Yang Zhan

    (Chinese Academy of Sciences
    Brain Cognition and Brain Disease Institute (BCBDI))

  • Nan Li

    (Chinese Academy of Sciences
    Shenzhen Institute of Synthetic Biology
    Chinese Academy of Sciences (CAS) Key Laboratory for Quantitative Engineering Biology)

  • Xiang Li

    (Chinese Academy of Sciences
    Guangdong Provincial Key Laboratory of Brain Connectome, Shenzhen Key Laboratory of Viral Vectors for Biomedicine)

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.

Suggested Citation

  • Liang Yang & Junfeng Shen & Chunhua Liu & Zhonghua Kuang & Yong Tang & Zhengjiang Qian & Min Guan & Yongfeng Yang & Yang Zhan & Nan Li & Xiang Li, 2023. "Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36543-8
    DOI: 10.1038/s41467-023-36543-8
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    References listed on IDEAS

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    1. Joseph T. Rodgers & Carlos Lerin & Wilhelm Haas & Steven P. Gygi & Bruce M. Spiegelman & Pere Puigserver, 2005. "Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1," Nature, Nature, vol. 434(7029), pages 113-118, March.
    2. Alexander Duncan & Mary P. Heyer & Masago Ishikawa & Stephanie P. B. Caligiuri & Xin-an Liu & Zuxin Chen & Maria Vittoria Micioni Di Bonaventura & Karim S. Elayouby & Jessica L. Ables & William M. How, 2019. "Habenular TCF7L2 links nicotine addiction to diabetes," Nature, Nature, vol. 574(7778), pages 372-377, October.
    3. Stephen J. Gardell & Meghan Hopf & Asima Khan & Mauro Dispagna & E. Hampton Sessions & Rebecca Falter & Nidhi Kapoor & Jeanne Brooks & Jeffrey Culver & Chris Petucci & Chen-Ting Ma & Steven E. Cohen &, 2019. "Boosting NAD+ with a small molecule that activates NAMPT," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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    1. Mengru Ma & Lian Yi & Yifei Pei & Qimin Zhang & Chao Tong & Manyu Zhao & Yuanhong Chen & Jinghan Zhu & Wanguang Zhang & Fan Yao & Pengyuan Yang & Peijing Zhang, 2024. "USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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