senolytics

Senolytics are a class of drugs or agents that selectively induce death of senescent cells, cells that have ceased dividing and accumulate with age. Cellular senescence is associated with a pro-inflammatory secretory profile known as the senescence-associated secretory phenotype (SASP), which is linked to tissue dysfunction and age-related diseases. By clearing senescent cells, senolytics aim to reduce SASP factors and improve tissue function, potentially extending healthspan in organ systems.

Many senolytics act by disabling pro-survival pathways that senescent cells rely on to resist apoptosis. Notable examples include the combination of dasatinib, a tyrosine kinase inhibitor, with quercetin, a plant flavonoid, which has shown senolytic activity in various cell types; navitoclax (ABT-263), a BCL-2 family inhibitor; and FOXO4-DRI, a peptide designed to disrupt a survival signal in senescent cells. Other approaches target heat shock protein 90 or other components of anti-apoptotic networks.

Evidence from animal studies shows that senolytics can reduce SASP burden, improve tissue function, and in some models extend healthspan and lifespan. Early human studies have demonstrated feasibility, safety, and changes in senescence biomarkers for some senolytics, with small trials in conditions such as idiopathic pulmonary fibrosis and chronic kidney disease reporting potential functional or biomarker benefits; however, robust, long-term clinical efficacy remains unproven.

Safety considerations include potential off-target effects, thrombocytopenia with navitoclax, and the need for intermittent dosing to mitigate adverse events. Biomarkers of senescence and clear patient selection criteria are active areas of research.

Current research focuses on expanding clinical data, improving selectivity, reducing side effects, and exploring combinations with other therapies to treat age-related diseases and promote healthy aging.