DEVELOPMENT OF SENOLYTIC THERAPIES FOR TREATMENT OF AGEING RELATED DISORDERS

Aging is a complex biological process signified by a decline in physiological functions and increased disease susceptibility. Among its various defining features, cellular senescence stands out as a significant hallmark. Senescence, a state where cells permanently stop dividing and accumulate as senescent cells, contributes to tissue dysfunction and inflammation, accelerating aging and related diseases. Various studies showed removing these cells can improve healthspan. Across senescent cell removal methods, the development of senolytics, agents that selectively target and eliminate senescent cells, has emerged as a promising approach. Senolytics face challenges like specificity, side effects, and unclear long-term effects, necessitating new developments. This doctoral thesis explores natural sources for new senolytics by screening a library of natural compounds. The screening displayed a plant extract-derived molecule as an effective senolytic for promoting healthy aging, showing efficacy in both in vitro and animal studies. The study shows the efficacy of the senolytic hit in aging intervention, detailing its impact across various organs in naturally aged mice. Through various senescence assays, the identified senolytic demonstrated effectiveness in prolonging lifespan and enhancing the health of vital organs.