Senolytics

technology

Drugs intended to kill senescent cells selectively, leaving dividing and quiescent cells intact. The class was defined in 2015 by Zhu, Kirkland and colleagues, who reasoned from the transcriptional profile of senescent cells that their survival depends on specific anti-apoptotic pathways and identified the leukaemia drug dasatinib and the plant flavonoid quercetin as a first combination; navitoclax and fisetin followed. In mice, intermittent dosing improves several functional measures and, in some studies, extends median lifespan. The human evidence in 2026 remains preliminary: the two first-in-human reports in 2019, in idiopathic pulmonary fibrosis and in diabetic kidney disease, were small, short and open-label — fourteen patients in the pulmonary study, with no control arm — and were designed to test feasibility and target engagement, not benefit. Intermittent dosing is the strategic point of the class: if senescent cells take weeks to reaccumulate, a drug need not be taken continuously, which changes the safety calculus for a healthy population.

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