Summary: A new long-term study in mice finds that continuous oral nicotine intake reshapes metabolism associated with aging and slows age-related motor decline. By acting on a gut-sphingolipid-energy axis, nicotine improved cellular energy balance, reduced harmful lipid buildup, preserved gut microbial diversity, and supported neuromuscular function. These results identify molecular pathways that could inform development of safer, non-addictive agents to support healthy aging, while underscoring that nicotine’s long-term safety in people remains unresolved.
Mice receiving nicotine throughout life showed integrated behavioral and metabolic features consistent with a biologically younger profile. The research maps nicotine’s systemic metabolic effects and highlights targets for interventions aimed at preserving mobility and metabolic health during aging.
Key Facts
- Metabolic reprogramming: Nicotine altered glycolipid and sphingolipid pathways, improving cellular energy balance and nicotinamide adenine dinucleotide (NAD+) availability.
- Motor protection: Nicotine-treated mice experienced delayed age-related motor decline and exhibited a more youthful behavior-metabolome signature.
- Therapeutic potential: The findings point to sphingolipid and cholinergic pathways as candidates for designing non-addictive metabolic modulators to support healthy aging and prevent sarcopenia.
Source: SIAT
Background: Aging is a systemic process marked by gradual energy imbalance and organ-specific metabolic deterioration. Loss of motor function is a major contributor to frailty and reduced independence in older adults. Identifying interventions that preserve energy homeostasis and neuromuscular resilience is a key priority for healthy aging research.
Nicotine is the primary bioactive alkaloid in tobacco. While smoking is clearly linked to accelerated cardiovascular and metabolic disease, some epidemiological data have suggested lower incidence of certain neurodegenerative diseases among smokers, raising questions about nicotine’s direct biological effects. This study examines whether nicotine itself can influence aging trajectories when delivered without the toxic combustion byproducts of smoking.
Published in Advanced Science, researchers led by Prof. LIU Xin’an and Prof. CHEN Zuxin at the Shenzhen Institutes of Advanced Technology (Chinese Academy of Sciences) report a 22-month longitudinal study in which mice consumed purified nicotine in drinking water. Doses were chosen to produce plasma nicotine levels comparable to human smokers but without combustion-related toxins.
The study combined precise 3D behavioral tracking, multi-organ metabolomics, gut microbiome sequencing, and cellular assays to comprehensively map nicotine’s systemic actions. Results show dose-dependent metabolic remodeling, concentrated in glycolipid and sphingolipid pathways, that supported improved energy homeostasis across tissues.
At the molecular level, nicotine exposure elevated NAD+ availability, limited accumulation of ceramides (lipids linked to metabolic stress), and modulated enzymes that control sphingolipid turnover. These adaptations were associated with preserved motor performance in older mice.
Longitudinal analysis of the gut microbiota revealed maintained microbial diversity in nicotine-treated animals and an increase in microbial metabolites tied to sphingolipid metabolism—metabolic signals previously implicated in muscle maintenance and sarcopenia prevention.
To quantify biological aging, the team integrated behavioral and metabolomic data into a combined Behavior‑Metabolome Age (BMAge) score. Nicotine-treated mice scored as biologically younger than controls, supporting a link between sphingolipid-energy regulation and maintained physical function.
Cell-based experiments in muscle-derived C2C12 cells and tissue analyses from aged mice confirmed that nicotine influences sphingomyelin synthases and neutral sphingomyelinases, shifting sphingolipid metabolism in ways that favor NAD+ production and energy metabolism while reducing harmful ceramide buildup.
The study offers the first systemic, life-long mapping of nicotine-driven metabolic remodeling during normal aging and identifies a gut-sphingolipid-energy axis that supports neuromuscular resilience. The authors emphasize that oral nicotine delivered in a controlled research setting avoids many tobacco toxicants, but they caution that nicotine’s long-term safety and complex biological effects in humans require careful evaluation.
By revealing specific metabolic pathways modulated by nicotine, the work provides a mechanistic foundation for developing “non-addictive cholinergic metabolic modulators” aimed at sustaining mobility and metabolic health in aging populations. The research team plans to continue systematic studies to clarify nicotine’s biological effects and to explore novel aerosolized or systemic compounds that target the same protective pathways without addictive potential.
About this aging, nicotine, and motor decline research news
Author: Qun LU
Source: SIAT
Contact: Qun LU – SIAT
Image: The image is credited to Neuroscience News
Original Research: Open access. “Nicotine Reprograms Aging-Related Metabolism and Protects Against Motor Decline in Mice” by LIU Xin’an et al., Advanced Science.
Abstract (Concise): Continuous oral nicotine intake over 22 months in mice attenuated age-associated motor decline without detectable pathological changes in major peripheral metabolic organs or immune dysfunction. Multi-organ metabolomics and network analysis identified nicotine-responsive shifts in glycolipid and sphingolipid metabolism that increased NAD+ availability and improved energy homeostasis. Longitudinal gut microbiota profiling showed preserved microbial composition and enhanced microbial-derived sphingolipid metabolites linked to muscle health. Cellular and tissue assays confirmed nicotine-driven regulation of sphingolipid enzymes, reduced ceramide accumulation, and improved motor outcomes. Integrated Behavior‑Metabolome Age scoring indicated a biologically younger phenotype in nicotine-treated mice. These results suggest that life‑long nicotine consumption can reprogram aging-associated metabolism through systemic sphingolipid homeostasis and confer resilience against age-related motor decline, while highlighting the need for careful assessment of long-term safety in humans.