Senolytics

Assembled from 26 blocks · 2 evidence · 15 related

1. Story
2. 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.
3. Knowledge
4. Cellular senescence
5. Senolytics
6. The missing surrogate endpoint for ageing
7. Connections
8. Cellular senescence
9. The missing surrogate endpoint for ageing
10. The first senolytic drugs are identified
11. Senolytics reach human patients for the first time
12. The hallmarks of ageing
13. Senolytics
14. Human diploid cells are shown to have a finite replicative capacity
15. The hallmarks of ageing are formalised
16. The first senolytic drugs are identified
17. Healthspan
18. Senolytics
19. TAME — Targeting Aging with Metformin
20. Epigenetic clocks
21. TAME is proposed as the first trial with an ageing endpoint
22. Senolytics reach human patients for the first time
23. Caloric restriction is reported to slow a pace-of-ageing measure
24. Evidence
25. Supports the definition of the senolytic drug class and the identification of dasatinib and quercetin as the first combination. V55 verification basis: not retrieved in this session.
26. Supports the first human administration of dasatinib plus quercetin, its open-label uncontrolled design and its physical-function rather than pulmonary-function findings. V55 verification basis: not retrieved; the fourteen-patient figure is recalled.