Senolytics

Main pharmacological senolytics:

Dasatinib + Quercetin (D+Q): the most-studied combination in humans. Dasatinib eliminates senescent endothelial and adipocytic cells; quercetin eliminates brain and endothelial ones. The intermittent 'hit-and-run' protocol (2 days/month) replicates the regeneration cycle of senescent cells. Fisetin: the most potent natural flavonoid senolytic, identified in screening of 10 polyphenols by Yousefzadeh et al. (2018). Navitoclax (ABT-263): potent BCL-xL/BCL-2 inhibitor. Effective but haematological toxicity (thrombocytopenia) limits its use. UBX0101, UBX1325: specific senolytics for osteoarthritis (Unity Biotechnology), intra-articular injection. FOXO4-DRI: synthetic peptide triggering selective apoptosis in senescent cells (in preclinical research).

Completed or ongoing human clinical trials: Idiopathic pulmonary fibrosis: D+Q showed significant functional improvement (Justice 2019). Diabetic kidney disease: D+Q reduced senescent cell burden in adipose tissue (Hickson 2019). Osteoarthritis: UBX0101 showed initial efficacy but less clear phase 2. Alzheimer's and cognitive decline: ongoing trials with D+Q and rapamycin. Long COVID: exploratory trials with fisetin for its anti-inflammatory + senolytic effect.

'Hit-and-run' philosophy: senolytics do not require chronic administration. Senescent cells are a gradually accumulated population; a periodic purge (every 1-3 months) can be enough to keep the tissue burden low. This dramatically reduces chronic side effects.

Monitoring: CRP, IL-6, p16INK4a (senescence marker), DEXA body composition, physical function. Specific biomarkers of senescent cells are an active research topic.