From collapse to comeback: Luteolin rejuvenates nucleus pulposus progenitor cells via SIRT1/ATF5–UPRmt to reverse intervertebral disc degeneration cascade

BACKGROUND: ), orchestrated by the Silent Information Regulator 1 (SIRT1)-Activating Transcription Factor 5 (ATF5) axis, plays a pivotal role in maintaining mitochondrial proteostasis. However, its involvement in IVDD remains insufficiently characterized. Luteolin (Lut), a naturally occurring flavonoid with well-documented antioxidant and anti-senescence properties, has emerged as a promising disease-modifying candidate. METHODS: activation, with or without SIRT1 knockdown. Finally, a puncture-induced rat IVDD model was employed to assess the therapeutic efficacy of Lut with imaging, histological, and behavioral analyses. RESULTS: activation, and bioenergetics. In vivo, Lut administration attenuated disc height loss, preserved extracellular matrix integrity and partially alleviated pain-like behaviors in rats with IVDD. CONCLUSION: axis as a critical mechanism mediating its protective effects. By restoring mitochondrial proteostasis and delaying NPPC senescence, Lut emerges as a promising disease-modifying strategy for IVDD management.