Senolytic Drugs: Dasatinib-Quercetin and Early Human Trials

The US label for dasatinib (Sprycel) lists certain chronic myeloid leukemia and acute lymphoblastic leukemia in adults and children. [1] Its label warns of fluid retention including pleural effusion, cardiovascular toxicity, pulmonary arterial hypertension, QT prolongation and harm to a fetus. [1] The most common reactions in people taking it for cancer include low blood counts, fluid retention, diarrhea, headache, rash, bleeding, shortness of breath, fatigue, nausea and muscle and bone pain. [1] Those are effects in people with cancer on routine dosing; trials of D+Q used intermittent schedules, but the drug's profile is the reason these studies are done under supervision. Label: approved medicine for leukemia only.

• Biomarkers are not outcomes. The kidney study counted senescent-cell markers in tissue, not kidney function or survival. [3] Likewise, the Alzheimer's study's fluid markers moved in mixed directions, and the authors said they needed confirmation in larger placebo-controlled studies. [5]
• The signals are disease-specific. The IPF open-label pilot reported better physical function, but it had no comparison group, and the later randomized pilot found no clear difference between groups on those measures while being underpowered. [2][4] The liver trial is the strongest randomized signal so far, but it is a single proof-of-principle trial in people with a specific liver disease, not healthy aging. [7]
• A negative result matters. In postmenopausal women, the primary bone endpoint did not differ from control, even though a secondary formation marker rose briefly. The authors described a possible effect in women with higher senescent-cell burden as exploratory. [6]
• Conflicts of interest. Several authors hold patents on senolytic drugs held by Mayo Clinic, which was disclosed in these papers. [3][6][7] That does not make the findings wrong, and it is a reason to want independent replication.
• Adverse events. The 2019 IPF pilot recorded respiratory symptoms, skin irritation or bruising and stomach discomfort among its non-serious events. [2] The liver trial reported adverse events in 82% with D+Q versus 43% with placebo, all described as self-limiting. [7]

None of these trials tested whether D+Q makes healthy people live longer or age more slowly. Mouse findings behind the field are preclinical and should not be transferred to people; see mouse results and what they prove.

Dasatinib is a cancer medicine with serious known risks, as the label shows. [1] It is prescription-only, and off-label experimentation is a matter for a prescriber, not for self-directed use; see off-label prescribing for longevity. People with heart, lung, liver or blood disorders, those who are pregnant, and anyone taking other medicines have reasons to be especially careful, since the label warns of fetal harm, heart effects and lung effects. [1] The supplement side of the story is covered at quercetin, fisetin and senolytic supplements.

Related: cellular senescence explained and senescence, senolytics and autophagy.