Related Experiment Video
Updated: Jan 31, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study
Jamie N Justice1, Anoop M Nambiar2, Tamar Tchkonia3
1Sticht Center for Healthy Aging and Alzheimer's Prevention, Internal Medicine - Gerontology and Geriatric Medicine, Wake Forest School of Medicine (WFSM), 1 Medical Center Blvd, Winston-Salem, NC 27157, United States.
Background:
Cellular senescence is a key mechanism that drives age-related diseases, but has yet to be targeted therapeutically in humans. Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal cellular senescence-associated disease. Selectively ablating senescent cells using dasatinib plus quercetin (DQ) alleviates IPF-related dysfunction in bleomycin-administered mice.
Methods:
A two-center, open-label study of intermittent DQ (D:100 mg/day, Q:1250 mg/day, three-days/week over three-weeks) was conducted in participants with IPF (n = 14) to evaluate feasibility of implementing a senolytic intervention. The primary endpoints were retention rates and completion rates for planned clinical assessments. Secondary endpoints were safety and change in functional and reported health measures. Associations with the senescence-associated secretory phenotype (SASP) were explored.
Findings:
Fourteen patients with stable IPF were recruited. The retention rate was 100% with no DQ discontinuation; planned clinical assessments were complete in 13/14 participants. One serious adverse event was reported. Non-serious events were primarily mild-moderate, with respiratory symptoms (n = 16 total events), skin irritation/bruising (n = 14), and gastrointestinal discomfort (n = 12) being most frequent. Physical function evaluated as 6-min walk distance, 4-m gait speed, and chair-stands time was significantly and clinically-meaningfully improved (p < .05). Pulmonary function, clinical chemistries, frailty index (FI-LAB), and reported health were unchanged. DQ effects on circulat.ing SASP factors were inconclusive, but correlations were observed between change in function and change in SASP-related matrix-remodeling proteins, microRNAs, and pro-inflammatory cytokines (23/48 markers r ≥ 0.50).
Interpretation:
Our first-in-humans open-label pilot supports study feasibility and provides initial evidence that senolytics may alleviate physical dysfunction in IPF, warranting evaluation of DQ in larger randomized controlled trials for senescence-related diseases. ClinicalTrials.gov identifier: NCT02874989 (posted 2016-2018).
Insights
This study explored senolytics (dasatinib plus quercetin) as a treatment for idiopathic pulmonary fibrosis (IPF). The senolytic intervention was feasible and showed promise in improving physical function in IPF patients.
Area of Science:
- Gerontology
- Pulmonology
- Pharmacology
Background:
- Cellular senescence is a key driver of age-related diseases, including idiopathic pulmonary fibrosis (IPF).
- Targeting senescent cells with senolytics like dasatinib plus quercetin (DQ) has shown potential in preclinical models.
- IPF is a progressive, fatal disease associated with cellular senescence.
Purpose of the Study:
- To evaluate the feasibility and safety of an intermittent senolytic intervention using dasatinib plus quercetin (DQ) in patients with IPF.
- To assess the impact of DQ on physical function, reported health, and senescence-associated secretory phenotype (SASP) in IPF patients.
Main Methods:
- An open-label, two-center pilot study involving 14 participants with stable IPF.
- Intermittent administration of DQ (dasatinib 100 mg/day, quercetin 1250 mg/day, three days/week for three weeks).
- Primary endpoints included retention and completion rates; secondary endpoints focused on safety, physical function, and SASP markers.
Main Results:
- 100% retention rate and high completion rate for clinical assessments, indicating feasibility.
- Significant and clinically meaningful improvements in physical function (6-min walk distance, gait speed, chair-stands time).
- Adverse events were mostly mild-to-moderate; no DQ discontinuation due to adverse events. SASP marker correlations with functional improvements were observed.
Conclusions:
- This first-in-human pilot study supports the feasibility of using senolytics for IPF.
- Senolytic intervention with DQ shows initial promise in alleviating physical dysfunction in IPF patients.
- Larger randomized controlled trials are warranted to further evaluate DQ for IPF and other senescence-related diseases.
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