Tier 3 — preclinical

Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease

Hickson LJ, Langhi Prata LGP, Bobart SA, et al.
EBioMedicine 2019 47:446-456

Bibliography

PubMed
PMID 31542391
DOI
10.1016/j.ebiom.2019.08.069
Funding
NIH and foundation funding (per abstract); specific bodies not detailed in the reviewed sections.
Competing interests
Not stated in the reviewed abstract.

Study snapshot

DesignOpen-label Phase 1 pilot: three days of oral dasatinib 100 mg plus quercetin 1000 mg, with adipose tissue, skin biopsies, and blood collected before and 11 days after treatment.
ModelAdults with diabetic kidney disease (human).
Sample9 participants.
InterventionDasatinib 100 mg plus quercetin 1000 mg orally, three days.
DurationThree days of dosing; assessed 11 days after completion.
EndpointsAdipose tissue senescent-cell markers (p16, p21, SA-beta-gal); Skin epidermal senescent-cell markers; Circulating SASP factors (IL-1alpha, IL-6, MMP-9, MMP-12)

What the study showed, in plain terms

Earlier senolytic trials showed people felt and functioned better, but no study had directly shown a senolytic drug actually reduced the number of senescent cells in human tissue. This trial tested that directly.

Nine adults with diabetic kidney disease took three days of dasatinib plus quercetin. Researchers biopsied fat and skin tissue before and 11 days after treatment to directly count senescent cells.

Senescent-cell markers dropped in both fat and skin tissue within 11 days of just three days of treatment, along with a drop in circulating inflammatory SASP factors — direct, tissue-level proof that a short senolytic pulse clears senescent cells in living humans.

Bottom line: not a fisetin study, but the direct human proof-of-mechanism behind the entire hit-and-run senolytic dosing model that fisetin trials, including AFFIRM, are built on.

Key findings

A single three-day pulse of dasatinib plus quercetin reduced senescent-cell markers in adipose tissue and skin, and reduced circulating SASP factors including IL-1alpha, IL-6, and MMP-9/12, within 11 days in nine adults with diabetic kidney disease — the first direct human tissue evidence that a senolytic pulse clears senescent cells.

What this study can and cannot tell us

Open-label Phase 1 pilot with only 9 participants and no control arm. Tests dasatinib plus quercetin, not fisetin. A single population (diabetic kidney disease); generalisability to other tissues and conditions is not established here.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability