senolyticscompounds

Senolytic compounds are substances that selectively induce death in senescent cells, cells that have permanently exited the cell cycle and often secrete pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). By reducing the burden of these cells in tissues, senolytics aim to mitigate tissue dysfunction and a range of age-related diseases, with the goal of improving healthspan.

Most senolytics target survival mechanisms that senescent cells rely on to resist apoptosis, collectively called senescent cell anti-apoptotic pathways (SCAPs). Notable examples include the combination of dasatinib and quercetin, which has shown senolytic activity in certain tissues and limited human studies; navitoclax (ABT-263), a BCL-2 family inhibitor with demonstrable senolytic effects but associated with hematologic toxicity; and FOXO4-DRI, a peptide intended to disrupt a survival signal in senescent cells. Additional candidates such as the flavonoid fisetin and various biotech-stage compounds are in development and early-stage testing.

As of now, senolytics are not approved as standard medical therapy. Several candidates have moved into early-phase clinical trials for aging-related conditions including frailty, osteoarthritis, and pulmonary fibrosis, but results have been mixed and safety concerns persist, particularly regarding off-target effects and toxicity. Ongoing research seeks to improve selectivity, optimize dosing strategies, and identify patient populations most likely to benefit.

Overall, senolytic compounds represent a growing area of biogerontology and translational medicine, with potential to complement therapies addressing aging and chronic disease, while requiring careful assessment of risks and long-term effects.