The Potential of Polyphenols in Modulating the Cellular Senescence Process: Implications and Mechanism of Action

作者：Larissa Della Vedova, Giovanna Baron, Paolo Morazzoni, Giancarlo Aldini, Francesca Gado · 发表于：Pharmaceuticals · 年份：2025 · DOI：10.3390/ph18020138 · 被引用次数：28 · 研究领域：Sirtuins and Resveratrol in Medicine、Telomeres, Telomerase, and Senescence、Antioxidant Activity and Oxidative Stress

Background: Cellular senescence is a biological process with a dual role in organismal health. While transient senescence supports tissue repair and acts as a tumor-suppressive mechanism, the chronic accumulation of senescent cells contributes to aging and the progression of age-related diseases. Senotherapeutics, including senolytics, which selectively eliminate senescent cells, and senomorphics, which modulate the senescence-associated secretory phenotype (SASP), have emerged as promising strategies for managing age-related pathologies. Among these, polyphenols, a diverse group of plant-derived bioactive compounds, have gained attention for their potential to modulate cellular senescence. Methods: This review synthesizes evidence from in vitro, in vivo, and clinical studies on the senolytic and senomorphic activities of bioactive polyphenols, including resveratrol, kaempferol, apigenin, and fisetin. The analysis focuses on their molecular mechanisms of action and their impact on fundamental aging-related pathways. Results: Polyphenols exhibit therapeutic versatility by activating SIRT1, inhibiting NF-κB, and modulating autophagy. These compounds demonstrate a dual role, promoting the survival of healthy cells while inducing apoptosis in senescent cells. Preclinical evidence indicates their capacity to reduce SASP-associated inflammation, restore tissue homeostasis, and attenuate cellular senescence in various models of aging. Conclusions: Polyphenols represent a promising c...