Senolytics and Dietary Phytochemicals: Exploring Anti-Aging Strategies and Mechanisms in Aging and Disease

Senolytic drugs (Anti-aging drugs) selectively eliminate senescent cells (SC), which are resistant to apoptosis and have up-regulated anti-apoptotic pathways that protect them from their inflammatory senescence(definition)-associated secretory phenotype (SASP). These drugs temporarily disable these pathways, inducing apoptosis in SCs with a tissue-destructive SASP. Initially identified through hypothesis-driven research, senolytics(definition) like Dasatinib, Quercetin, Fisetin, and Navitoclax have shown in preclinical models to delay, prevent, or alleviate frailty, cancers, and various disorders as well as complications from organ transplantation. Senolytics like Azithromycin and Quercetin, which have anti-aging properties, are proposed as potential treatments. Since 2015, several senolytics have progressed to clinical trials. Recent studies link chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) to accelerated aging mechanisms, including cellular senescence. COPD's diversity, with its range of phenotypes, implies that lung aging may play varying roles in different phenotypes, complicating the identification of COPD patients who might benefit from senolytics. Preclinical evidence suggests senolytics reduce all-cause mortality, enhance physical function and resilience, and alleviate diseases across various organs, even in elderly patients. Diet provides energy, nutrition, and enjoyment. Studies show that major dietary components regulate aging and longevity. The potential for other dietary ingredients to prevent aging and extend longevity is intriguing. Recent findings suggest that certain plant-based ingredients can extend longevity by regulating metabolism, targeting TRP channels, reactive oxygen species (ROS), promoting mitophagy, influencing senescence pathways, and modulating circadian rhythms. Understanding these may help develop interventions for aging and related diseases. Calorie restriction and dietary manipulations that reduce ROS and inflammation while promoting autophagy(definition) can extend lifespan in model organisms. Some phytochemicals also extend lifespan in animals. This review examines the role of senescent cells in aging and disease, methods for discovering and refining senotherapeutics, and the status of senolytic preclinical and clinical trials and highlights anti-aging phytochemicals studied in cells, animals, and humans, exploring their cellular and molecular mechanisms.