SenolyticsA compound intended to clear senescent cells: older cells that have stopped dividing but remain in tissue.
Senolytics: What the Human Trials Show
Three randomized senolytic trials in humans have published results. None of them tested a supplement you can buy, at a dose anyone sells, in a healthy population. This page sets out what each one measured and what it found.
Senescent cells stop dividing but do not die, and they secrete inflammatory signals. They accumulate with age. A senolytic is a compound intended to clear them selectively. The idea is coherent, the animal work is substantial, and it is one of the more interesting hypotheses in aging biology.
It is also the category where the distance between what has been tested and what is being sold is widest. The compounds studied in humans are a prescription cancer drug given intermittently, and an injection into the eye. The compounds on sale as senolytics are flavonoids whose senolytic evidence is entirely in mice.
Every trial and grade below links out to its source. Nothing here is EBL restating a finding it has not read.
The three randomized trials
Dasatinib plus quercetin, bone metabolism
Farr, Nature Medicine, 2024 · phase 2 · n=60
Primary endpointThe one outcome a trial names in advance as its main test. Results on other outcomes carry less weight. not met
The largest randomized senolytic trial published. Postmenopausal women received intermittent dasatinib plus quercetin. The primary endpointThe outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score., change in the bone resorption marker CTx at 20 weeks, did not differ between groups (P = 0.611). A secondary bone formation marker rose at 2 and 4 weeks but was no different from control at 20 weeks. No serious adverse events occurred. An exploratory subgroup analysis in women with the highest senescent cell burden reported effects; a subgroup finding after a missed primary endpoint generates a hypothesis rather than settling one.
A single injection into the eye of a BCL-xL inhibitor, in patients who had responded poorly to existing treatment. The primary objective was safety, not efficacy; efficacy was secondary. Serious adverse events were comparable between arms. This is a prescription drug delivered intravitreally for an eye disease, and it demonstrates that the senolytic mechanism is being tested seriously in humans. It says nothing about an oral supplement taken for aging.
Nambiar, EBioMedicine, 2023 · randomized pilot · n=12
Feasibility and adverse events
A randomized placebo-controlled pilot in idiopathic pulmonary fibrosis, run to establish adverse event profile and feasibility for a future efficacy trial rather than to measure benefit. Twelve participants. No serious adverse events were attributed to the combination, though sleep disturbance and anxiety appeared in four of six participants on the drug and none of six on placeboAn inactive substitute made to look like the real treatment, so participants cannot tell which one they received..
Justice 2019 is cited widely as evidence that senolytics work in people. It was an open-labelEveryone in the trial knows which treatment they are receiving, so expectations can shape the results, especially for symptoms people report themselves., single-arm, first-in-human pilot in fourteen patients with idiopathic pulmonary fibrosis. There was no control group and no blinding, which is why the same investigators later ran the randomized pilot above and said the absence of a control had limited what the first study could support. It is a real and useful study. It is not a randomized controlled trialPeople are assigned to the treatment or a comparison by chance, so the groups differ only in what they received. It is the design that can show cause and effect. and cannot carry a grade under the EBL rubric. (PMID 30616998)
What is sold, and how it is graded
None of the three trials above used a compound sold as a senolytic supplement. Dasatinib is a prescription tyrosine kinase inhibitor. UBX1325 is an investigational drug injected into the eye. Quercetin appears in the dasatinib combination and has never been tested alone as a senolytic in humans.
A Grade D on Route 1No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale. means untested in humans, not tested and failed. It changes when the testing happens. For fisetin that means a published, randomized, controlled human trial of fisetin itself, at a stated dose, reporting a prespecified primary endpoint. A positive primary endpoint on an objectively measured functional outcome or a hard clinical endpointAn outcome that matters directly to a person and is counted without judgment, such as death, heart attack, stroke or fracture. would support a higher grade. A positive result on a surrogate markerA lab value or measurement used in place of the outcome that matters, such as LDL cholesterol standing in for heart attacks. Moving a surrogate does not always move the outcome. alone would cap at Grade B under the EBL rubric regardless of trial quality.
A trial that reports safety, or misses its primary endpoint and reports a favorable subgroup, would not move the grade. That is what happened in the bone metabolism trial above, for a different compound.