DataVXAdvanced SciencePaper
journal article·2025-10Open access

Nicotine Reprograms Aging‐Related Metabolism and Protects Against Motor Decline in Mice

Shuhui Jia, Xiaoyuan Jing, Ruoxi Wang, Mengke Su, Pei Wang, Yingxin Feng, Xiaohu Ren, Longfang Tu, Ping Wei, Zhen Lu, Yicong Jia, Feng Hong, Zhizhun Mo, Jiemeng Zou, Kang Huang, Caiyun Yan, Qianhui Zou, Liang Wang, Guoping Zhong, Zhi Zeng, Qiuliyang Yu, Wen Su, Xifei Yang, Fan Pan, Jianzhi Wang, Liping Wang, Lijun Kang, Paul J. Kenny, Zuxin Chen, Xin‐an Liu

Advanced Science· Volume 12· Issue 40
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Source abstract

Abstract

Abstract The effects of nicotine on aging‐related motor and cognitive decline remain controversial due to limited empirical evidence. Here, mice are permitted to orally consume nicotine over a 22‐month period and observed attenuated motor decline without pathological alterations in major metabolism‐related peripheral organs or immune system dysfunction. Multi‐organ metabolomic profiling and network analysis of aged mice (24 months old) identified nicotine‐responsive pathways related to glycolipid metabolism and energy homeostasis. Dynamic gut microbiota profiling via series expression miner‐based longitudinal analysis reveals that nicotine consumption preserved microbiota composition and altered microbial‐derived metabolites associated with the sphingolipid pathway, known to regulate age‐related muscle dysfunction and sarcopenia. Assays in aged mice and C2C12 cells confirmed that nicotine regulates sphingolipid turnover, particularly via sphingomyelin synthases and neutral sphingomyelinases, to enhance nicotinamide adenine dinucleotide availability and energy metabolism. These metabolic adaptations correlated with reduced ceramide accumulation and improved motor function. Behavior‐Metabolome Age (BMAge) score confirmed a biologically younger phenotype in the nicotine‐treated mice. Together, these findings suggest that life‐long oral nicotine consumption reprograms aging‐associated metabolism through regulation of systemic sphingolipid homeostasis, conferring resilience against age‐related motor decline.
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Research context

OpenAlex topics: Tryptophan and brain disorders · Diet and metabolism studies · Gut microbiota and health

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Guangdong Provincial Key Laboratory of Brain Connectome and Behavior Brain Cognition and Brain Disease Institute (BCBDI) Shenzhen‐Hong Kong Institute of Brain Science Shenzhen Institutes of Advanced Technology (SIAT) Chinese Academy of Sciences (CAS) Shenzhen 518055 China

Shenzhen Key Laboratory of Drug Addiction Shenzhen Neher Neural Plasticity Laboratory Brain Cognition and Brain Disease Institute Shenzhen‐Hong Kong Institute of Brain Science Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China

Sino‐European Center of Biomedicine and Health Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China

Department of Pathology Shenzhen University Shenzhen 518055 China

Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology Shenzhen Center for Disease Control and Prevention Shenzhen 518055 China

Centre for Cancer Immunology Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China

Shenzhen Bayone Biotech CO., Ltd. Shenzhen 518055 China

Research Center for Primate Neuromodulation and Neuroimaging Shenzhen Key Laboratory for Molecular Imaging Guangdong Provincial Key Laboratory of Biomedical Optical Imaging Technology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China

Institute of Clinical Pharmacology School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510080 China

Department of Pathology Renmin Hospital of Wuhan University Wuhan 430060 China

Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College Huazhong University of Science and Technology Wuhan 430060 China

Department of Neurology of the Fourth Affiliated Hospital and School of Brain Science and Brain Medicine, NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University School of Medicine Yiwu 322000 China

Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Funding

Basic and Applied Basic Research Foundation of Guangdong Province

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