senolytica

Senolytica, or senolytics, are a class of pharmacological agents designed to selectively induce death in senescent cells—cells that have stopped dividing in response to stress or damage. By reducing the burden of these cells and the inflammatory secretions they produce, senolytics aim to improve tissue function and counter certain aspects of aging and age-related diseases in preclinical and some human studies.

Most senolytics act by targeting pro-survival pathways that are upregulated in senescent cells, making these cells more dependent on certain anti-apoptotic signals. In healthy cells, these pathways are less essential, allowing senolytics to preferentially trigger apoptosis in senescent cells. This selective vulnerability is a key feature of this therapeutic approach, though the specific targets and mechanisms can vary between compounds.

Several compounds and strategies have been studied. The combination of dasatinib and quercetin is among the most studied senolytics, showing senolytic activity in multiple model systems and in small human trials. Navitoclax (ABT-263) is a BCL-2 family inhibitor with potent senolytic effects but carries risks such as hematologic toxicity, including thrombocytopenia. Other approaches include FOXO4-DRI, a peptide designed to disrupt pro-survival interactions in senescent cells, and fisetin, a plant-derived flavonoid with reported senolytic activity in preclinical and early clinical research.

In animals, senolytics have been associated with reduced senescent cell burden and improvements in tissue function and延 disease phenotypes. Human data are still early, with small trials indicating potential benefits in frailty and physical performance, but definitive evidence awaits larger, longer-term studies. Safety concerns and the heterogeneity of senescent cells present ongoing challenges for development. See also aging, SASP, longevity, and cellular senescence.