A first-in-human, open-label pilot study evaluated the feasibility and potential of senolytics (dasatinib plus quercetin, DQ) in idiopathic pulmonary fibrosis (IPF). The study enrolled 14 participants with stable IPF, who received intermittent DQ treatment (100 mg/day dasatinib and 1250 mg/day quercetin, three days per week for three weeks). The primary endpoints were retention and completion of planned assessments, with secondary endpoints including safety and changes in physical and reported health measures. All 14 participants completed the study with 100% retention, and no DQ discontinuation. Physical function, measured by 6-minute walk distance (6MWD), 4-m gait speed, and chair-stands time, showed statistically significant and clinically meaningful improvements (p < 0.05). Pulmonary function, clinical chemistries, frailty index (FI-LAB), and reported health remained unchanged. While effects of DQ on circulating senescence-associated secretory phenotype (SASP) factors were inconclusive, correlations were observed between changes in function and SASP-related matrix-remodeling proteins, microRNAs, and pro-inflammatory cytokines (23/48 markers, r ≥ 0.50). The study supports the feasibility of senolytic interventions in IPF and provides initial evidence that DQ may alleviate physical dysfunction in IPF. However, further evaluation in larger randomized controlled trials is warranted. Adverse events were mostly mild to moderate, with respiratory symptoms, skin irritation, and gastrointestinal discomfort being most frequent. No significant changes in laboratory tests or pulmonary function were observed. The study highlights the potential of senolytics in treating age-related diseases, including IPF, by targeting cellular senescence. The findings suggest that DQ may reduce senescent cell burden and improve lung function in IPF, warranting further investigation in larger trials.A first-in-human, open-label pilot study evaluated the feasibility and potential of senolytics (dasatinib plus quercetin, DQ) in idiopathic pulmonary fibrosis (IPF). The study enrolled 14 participants with stable IPF, who received intermittent DQ treatment (100 mg/day dasatinib and 1250 mg/day quercetin, three days per week for three weeks). The primary endpoints were retention and completion of planned assessments, with secondary endpoints including safety and changes in physical and reported health measures. All 14 participants completed the study with 100% retention, and no DQ discontinuation. Physical function, measured by 6-minute walk distance (6MWD), 4-m gait speed, and chair-stands time, showed statistically significant and clinically meaningful improvements (p < 0.05). Pulmonary function, clinical chemistries, frailty index (FI-LAB), and reported health remained unchanged. While effects of DQ on circulating senescence-associated secretory phenotype (SASP) factors were inconclusive, correlations were observed between changes in function and SASP-related matrix-remodeling proteins, microRNAs, and pro-inflammatory cytokines (23/48 markers, r ≥ 0.50). The study supports the feasibility of senolytic interventions in IPF and provides initial evidence that DQ may alleviate physical dysfunction in IPF. However, further evaluation in larger randomized controlled trials is warranted. Adverse events were mostly mild to moderate, with respiratory symptoms, skin irritation, and gastrointestinal discomfort being most frequent. No significant changes in laboratory tests or pulmonary function were observed. The study highlights the potential of senolytics in treating age-related diseases, including IPF, by targeting cellular senescence. The findings suggest that DQ may reduce senescent cell burden and improve lung function in IPF, warranting further investigation in larger trials.