Tier 3 — preclinical

Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study

Justice JN, Nambiar AM, Tchkonia T, et al.
EBioMedicine 2019 40:554-563

Bibliography

PubMed
PMID 30616998
DOI
10.1016/j.ebiom.2018.12.052
Funding
NIH; Claude D. Pepper Older Americans Independence Centers (Wake Forest School of Medicine, UTHSCSA); Translational Geroscience Network.
Competing interests
Not stated in the reviewed abstract.

Study snapshot

DesignTwo-centre, open-label pilot study of intermittent oral dasatinib plus quercetin (three days per week over three weeks) in adults with idiopathic pulmonary fibrosis.
ModelAdults with stable idiopathic pulmonary fibrosis (human).
Sample14 participants.
InterventionDasatinib 100 mg/day plus quercetin 1250 mg/day, three days per week, for three weeks.
DurationThree weeks of intermittent dosing.
EndpointsRetention and completion rates (feasibility); Safety and adverse events; 6-minute walk distance; 4-metre gait speed; Chair-stands time; Circulating SASP factors

What the study showed, in plain terms

This was the first time any senolytic drug combination was tested in humans at all. Researchers wanted to know whether clearing senescent cells was even feasible and safe in people with a serious lung disease linked to cellular ageing.

Fourteen adults with idiopathic pulmonary fibrosis took intermittent dasatinib plus quercetin — three days a week for three weeks — and were monitored for safety, tolerability, and physical function.

All 14 participants completed the intervention with no drug discontinuations. Physical function — walking distance, gait speed, and chair-stand time — improved significantly. Effects on inflammatory SASP markers were inconclusive on their own, but correlated with the functional improvements.

Bottom line: not a fisetin study, and not controlled, but historically important — it proved a senolytic drug combination could be safely and feasibly given to older, sick adults, opening the door to the fisetin trials that followed.

Key findings

Intermittent dasatinib plus quercetin was feasible and well tolerated in 14 adults with idiopathic pulmonary fibrosis, with 100% retention. Physical function measures (6-minute walk distance, gait speed, chair-stands time) improved significantly; effects on circulating SASP factors were inconclusive alone but correlated with functional change.

What this study can and cannot tell us

Open-label, uncontrolled, unblinded pilot with only 14 participants. Tests dasatinib plus quercetin, not fisetin. Cannot establish efficacy on its own — a feasibility and safety pilot only.

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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