Dasatinib plus quercetin (D+Q)

Dasatinib plus quercetin, usually shortened to D+Q, is the best-known "senolytic" combination: a leukaemia drug paired with a plant flavonoid to kill off worn-out senescent cells. In mice it looks remarkable. In people, most studies have been tiny and most had no control group, the one sizeable randomised trial missed its main goal, and in healthy adults several biological-age markers moved the wrong way.

Healthy adults should not take D+Q. Dasatinib is a prescription cancer drug, the human evidence of benefit is limited to one small, unrepeated liver-biopsy trial in people with fatty-liver disease, and the only study in healthy adults found several biological-age markers moving the wrong way.

What it is and why the two are paired

Senescent cells are damaged cells that stop dividing but do not die; they survive by switching on anti-death (anti-apoptotic) defences and leak inflammatory signals as they accumulate with age (see Cellular senescence). Senolytics briefly disable those defences so the cell's own self-destruct machinery can finish the job.

Dasatinib is a leukaemia drug that blocks pro-survival signals. Quercetin is a plant flavonoid sold as a supplement. They are paired because they work best on different kinds of senescent cells. In the original laboratory study, dasatinib cleared senescent human fat-cell precursors, while quercetin worked better against senescent cells from blood-vessel linings, and the combination lowered the senescent-cell load in aged mice.^[1]

In the lab, cartilage results are encouraging, but they come from donated cells and tissue pieces, not from people. On cartilage cells from older donors and tissue pieces from knees with early osteoarthritis, D+Q cleared senescent cells and switched the remaining cells back toward making cartilage. The rebuilding effect came mainly from dasatinib alone.^[2]

The human studies, one by one

The first human result needed correcting. The first study to show senescent cells being cleared in people was an open-label phase 1 pilot in nine patients with diabetic kidney disease, given three days of D+Q. It reported fewer senescent cells in fat and skin afterwards.^[3] The next year the authors published a corrigendum that re-analysed the raw data and revised some of its conclusions.^[4]
The randomised bone trial missed. In a randomised phase 2 trial, 60 postmenopausal women took D+Q intermittently for 20 weeks or received no treatment. The main goal, slowing bone breakdown, was not met: a blood marker of bone breakdown did not differ from the untreated group. A bone-building marker rose by about 16% in the first month, then fell back to the untreated group's level by week 20. There were no serious side effects. In an exploratory look at the third of women with the highest levels of the senescence marker p16 in a type of immune cell (T cells), forearm bone density rose by about 3%, a lead worth testing, not a result.^[5]
A small randomised liver trial met its goal, for now. In 31 adults with scarring fatty-liver disease (fibrotic MASH, metabolic dysfunction-associated steatohepatitis), about half of those given intermittent D+Q for 21 weeks showed at least one stage less liver scarring on biopsy, against one in fourteen on placebo. Side effects were more common on D+Q, though all passed on their own. The result rested on few responders and lost significance under the most pessimistic handling of missing data, so the authors treat it as preliminary until a larger trial repeats it; two of them have a financial interest in Mayo Clinic senolytic patents.^[6]
Lung scarring: no clear benefit once a placebo group was added. An early study in people with idiopathic pulmonary fibrosis had no comparison group and reported better walking and physical function after D+Q.^[7] The same team repeated it in 12 patients, half given placebo. Walking, lung and frailty measures did not appear to differ between the groups, though the study was too small to be sure. Sleep problems and anxiety showed up in four of the six people on D+Q and in none of the six on placebo.^[8]
Memory: two tiny uncontrolled pilots. A twelve-person pilot gave intermittent D+Q to older adults at risk of Alzheimer's disease for twelve weeks. It was well tolerated, with no serious side effects related to the drugs, but it was single-arm and open-label with no control group. Scores on a 30-point memory-and-thinking screening test rose by 1.0 point, a change compatible with anything from a 0.7-point fall to a 2.7-point rise; the inflammatory marker tumour necrosis factor-alpha fell by 3%, with a range running from a 13% fall to a 7% rise.^[9] An earlier five-person pilot in mild Alzheimer's disease checked whether the drugs reach the brain at all. Dasatinib turned up in the fluid around the brain in four of the five, at under 1% of its blood level, and quercetin was not detected. Thinking tests and brain scans did not change; two markers of brain inflammation and injury rose while some other inflammatory signals trended down. The authors say the rise could mean senescent cells were being cleared, or simply that the drugs triggered inflammation, and that later samples would be needed to tell which; two of the authors hold senolytic patents.^[10] Its placebo-controlled follow-up, with about 48 participants, has not yet reported.^[11]

The warning for healthy people

A phase 1 study followed 19 healthy adults aged 43 to 87 through six months of D+Q, measuring DNA-methylation "clocks", lab estimates of biological age. All three first-generation clocks showed accelerated aging at three months, at the kind of doses people take on their own; a second-generation clock (PhenoAge) moved too, and a methylation estimate of telomere length fell.^[12]

Read it carefully; the tables say more than the summary:

The clocks best validated against health outcomes, GrimAge and DunedinPACE, did not move.
The acceleration on two clocks had returned to baseline by six months; two others (Hannum and PhenoAge) had not, and the telomere estimate had not recovered by six months.
The follow-on group that added fisetin was a different, only partly overlapping set of people. Its apparent "mitigating" effect is a comparison across two small studies, and on the clock that drove the original finding its age estimate rose significantly.

None of this shows that senolytics "age you". It is a concrete reason not to self-administer them: a tool designed to clear sick cells can stress healthy ones, and nineteen people cannot tell you how much.

More reasons for caution

Two laboratory findings point the same way. Healthy young blood-vessel muscle cells exposed to D+Q briefly took on the nuclear and chromatin features of senescent cells, recovering only after the drugs were withdrawn.^[13] And in rodents with acute kidney injury caused by folic acid, D+Q worsened the damage.^[14] Clearing senescent cells is context-dependent, and "more" is not safely "better".

What to do

Don't self-administer D+Q. Dasatinib is a prescription leukaemia drug, and no trial has shown a benefit in healthy people.
Don't treat a quercetin supplement as a stand-in. The human D+Q studies above all used it together with dasatinib.
If you want to act on senescent cells, use the levers with human data. Calorie restriction and treating insomnia have randomised-trial support on blood markers; see Cellular senescence.