Senolytic Drug Development

Cellular senescence is a hallmark of aging because senescent cells (SnCs) accumulate with age and play a causative role in many age-related diseases. Selectively eliminating SnCs has been emerging as a new strategy for treating age-related diseases and extending healthspan. Small molecules that targeting different SnC anti-apoptotic pathways (SCAPs) to selectively kill SnCs are termed senolytics. Up to date, several classes of senolytic agents, including naturally occurring compounds and their derivatives, and targeted therapeutics, have been identified. Here we discuss the biological significances of cellular senescence in aging, and summarize some of the known naturally occurring and targeted senolytic agents and their targets. As most of the known naturally occurring compounds or targeted senolytics have limitations to be developed as therapeutics for human applications, development of more specific and potent senolytic agents that can reduce the on-target and/or off-target toxicity of senolytics, is urgently needed to improve healthy aging in humans.