Microwave-Assisted Propolis Extract Attenuates Oxidative-Stress- and Replicative Senescence via NRF2 and Wnt/β-Catenin–TERT Activation in Human Dermal Fibroblasts

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (<i>NQO1</i>, <i>GCLM</i>), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (<i>CDKN2A</i>, <i>CDKN1A</i>, <i>IL6</i>), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited <i>MMP1</i> expression, restored <i>COL1A1</i>, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating <i>WNT3A</i> and <i>LEF1</i> while suppressing <i>DKK1</i>, and increased <i>TERT</i> expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin-TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging.