Background and Purpose: Astrocyte senescence plays a critical role in age-related cognitive decline and Alzheimer’s disease. This study investigated whether baicalein can delay astrocyte senescence and alleviate age-related cognitive decline. Meanwhile we explored the potential mechanisms by focusing on alterations in lipid metabolism. Experimental Approach: The anti-astrocyte senescence effects of baicalein were evaluated using SA-β-gal staining,cell cycle assay and so on. The molecular mechanisms underlying the effects of baicalein were elucidated by integrating transcriptomics and liquid chromatography-mass spectrometry (LC-MS) metabolomic approaches. The anti-senescence effects of key metabolites were verified in primary astrocytes. Subsequently, we confirmed the effects of baicalein on cognitive decline, astrocyte senescence, and key lipid metabolites levels in naturally aged mice model. Key Results: Our study demonstrate that baicalein protects against astrocyte injury and senescence. Transcriptomic - metabolomic integration reveals that lipid metabolism as a key pathway modulated by baicalein, with oxoglutaric and fumaric acid emerging as crucial metabolites. Also oxoglutaric and fumaric acid directly attenuate astrocyte senescence. In naturally aged mice, baicalein treatment significantly improved cognitive dysfunction, mitigated astrocyte senescence, and increased oxoglutaric acid levels. Collectively, these findings indicate that bacalein delays astrocyte senescence both in vitro and in vivo, and it may correlated with oxoglutaric and fumaric acid levels. Conclusion and Implications: This study demonstrates that baicalein effectively attenuates astrocyte senescence and ameliorates age-related cognitive dysfunction, likely through modulation of oxoglutaric and fumaric acid metabolism. Our work underscores the pivotal role of metabolic dysregulation in astrocyte senescence, revealing potential targets to combat age-associated neurological disorders.