Nature metabolismOct 1, 2026

Senolytic drugs dasatinib and quercetin in fatty liver disease linked to metabolism: a first controlled trial

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 3, 2026

Abstract

In a phase-2 trial, 47% of participants receiving dasatinib plus quercetin showed fibrosis improvement compared to 7% with placebo.

Intermittent senolytic therapy with dasatinib plus quercetin is associated with a higher rate of metabolic dysfunction-associated steatohepatitis (MASH) resolution (53% vs. 7%).
A significant reduction in the NAFLD Activity Score was observed in the treatment group compared to the placebo group (-1.43 vs. -0.39).
Single-nucleus RNA sequencing indicated decreased levels of senescence and fibrotic gene signatures in participants treated with dasatinib plus quercetin.
Adverse events occurred more frequently in the treatment group (82% vs. 43%), but were all self-limiting.
The findings suggest a potential therapeutic role for senolytic therapy in treating fibrotic MASH, warranting further investigation.

Simplified

Cellular senescence plays an important role in hepatic inflammation and fibrosis^1-3. However, whether senescence represents a potential therapeutic target in humans with metabolic dysfunction-associated steatohepatitis (MASH) remains unexplored. Here we report the results of a phase-2, double-blind, randomized, placebo-controlled trial of intermittent senolytic therapy with dasatinib plus quercetin (D + Q) in participants with fibrotic MASH. Thirty-one participants (median age 56 years; 76% male; 58% with type 2 diabetes) were randomized (1:1) to receive D + Q (dasatinib 100 mg per day plus quercetin 1,000 mg per day) or placebo for three consecutive days per week over 3 weeks, repeated across three 7-week cycles. The primary endpoint, ≥1 stage fibrosis improvement without MASH worsening on paired liver biopsies, is achieved in 47% of D + Q-treated participants versus 7% with placebo (P = 0.02). MASH resolution occurs more frequently with D + Q than placebo (53% versus 7%; P = 0.02), with a greater reduction in NAFLD Activity Score (-1.43 ± 1.22 versus -0.39 ± 0.77; P = 0.012). Single-nucleus RNA sequencing demonstrates decreased senescence and fibrotic gene signatures and reduced fibrogenic cell populations in the D + Q group. Although adverse events are more frequent in the D + Q group (82% versus 43%), these are all self-limiting. Overall, this proof-of-principle trial supports the need for future trials of senolytic therapy in fibrotic MASH. ClinicalTrials.gov identifier: NCT05506488 .