Abstract
Human dental pulp stem cells (hDPSCs) senescence impairs their proliferation and osteogenic differentiation, critical for dental stem cell therapy. This study evaluated the effects of Resveratrol on the senescence of hDPSCs to explore new therapeutic strategies. Metabolomic analysis identified age-related metabolic differences in dental pulp tissues, with enriched pathways linked to Resveratrol. In vitro, Resveratrol improved proliferation, delayed senescence, promoted osteogenic differentiation, and enhanced mitochondrial autophagy, function, and biogenesis in senescent hDPSCs, reducing mitochondrial damage and oxidative stress. Mechanistically, silencing PINK1 or PGC-1α reversed Resveratrol-mediated promotion of proliferation, osteogenesis, and senescence suppression. Blocking SIRT1 abrogated its effects on mitochondrial quality control. These findings highlight Resveratrol's potential to mitigate hDPSCs senescence via SIRT1-dependent mitochondrial regulation, offering insights for age-related dental regenerative therapies.