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Published on: February 10, 2012
Nicotine Reprograms Aging-Related Metabolism and Protects Against Motor Decline in Mice
Shuhui Jia1, Xiaoyuan Jing1, Ruoxi Wang1
1Guangdong 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.
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.
Insights
Long-term oral nicotine intake in mice attenuated age-related motor decline by reprogramming metabolism. Nicotine preserved gut microbiota and improved energy homeostasis, suggesting a potential role in healthy aging.
Area of Science:
- Gerontology and Metabolic Research
- Neuroscience and Aging
- Microbiome and Metabolism
Background:
- The impact of nicotine on aging-related cognitive and motor decline is not well understood.
- Limited empirical evidence exists regarding nicotine's long-term effects on aging processes.
- Investigating nicotine's influence on metabolism and aging could reveal novel interventions.
Purpose of the Study:
- To investigate the effects of long-term oral nicotine consumption on motor function and metabolism in aging mice.
- To explore the underlying molecular mechanisms, including metabolic pathways and gut microbiota alterations.
- To determine if nicotine consumption confers resilience against age-related motor decline.
Main Methods:
- Mice consumed nicotine orally for 22 months.
- Multi-organ metabolomic profiling and network analysis were performed on aged mice.
- Longitudinal gut microbiota profiling and sphingolipid pathway analysis were conducted.
- Assays in mice and C2C12 cells examined sphingolipid turnover and energy metabolism.
- Behavior-Metabolome Age (BMAge) score was used to assess biological age.
Main Results:
- Nicotine consumption attenuated motor decline without causing pathological changes in major organs or immune dysfunction.
- Metabolomic analysis identified nicotine-responsive pathways in glycolipid metabolism and energy homeostasis.
- Nicotine preserved gut microbiota composition and altered microbial metabolites in the sphingolipid pathway.
- Nicotine regulated sphingolipid turnover, enhancing nicotinamide adenine dinucleotide availability and energy metabolism.
- Reduced ceramide accumulation and improved motor function were observed, with nicotine-treated mice showing a younger biological phenotype (BMAge score).
Conclusions:
- Life-long oral nicotine consumption reprograms aging-associated metabolism by regulating systemic sphingolipid homeostasis.
- Nicotine confers resilience against age-related motor decline through metabolic adaptations.
- Findings suggest a potential therapeutic avenue for mitigating age-related motor dysfunction.
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