Introduction Hayflick and Moorhead first demonstrated cell senescence as the irreversible growth arrest of cells after prolonged cultivation. Telomere shortening and oxidative stress are the fundamental mechanisms that drive cell senescence. Increasing studies have shown that TMAO is closely associated with cellular aging and age-related diseases. An emerging body of evidence from animal models, especially mice, has identified that TMAO contributes to senescence from multiple pathways and appears to accelerate many neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. However, the specific mechanism of how TMAO speeds aging is still not completely clear. Material and methods In this review, we summarize some key findings in TMAO, cell senescence, and age-related diseases. We focused particular attention on the potential mechanisms for clinical transformation to find ways to interfere with the aging process. Conclusion TMAO can accelerate cell senescence by causing mitochondrial damage, superoxide formation, and promoting the generation of pro-inflammatory factors.