Exploring the Senotherapeutic Potential of Polyphenols in Aging and Disease: A Literature Review

Aging is associated with an increased risk of developing many age-related diseases (ARDs), which are of major global health concern. In recent years, cellular senescence, characterized by cell cycle arrest and development of a senescence-associated secretory phenotype (SASP), has emerged as a key mechanism of aging and ARDs and has been increasingly explored as a promising therapeutic target. Among dietary bioactive ingredients, fisetin and quercetin have gained attention because of their potential to act as senolytics and senomorphics. This narrative literature review summarizes existing evidence exploring the potential of fisetin and quercetin to modulate senescence and SASP biomarkers in animal models of aging and progeria, as well as in interventional studies involving human subjects with geriatric syndromes and/or various ARDs. It also provides a brief overview of the molecular mechanisms of senescence and attempts to identify potential drivers and barriers for the clinical translation of those nutrients.