Can Clearing Senescent Cells Reduce Liver Scarring

Edited and approved by Stephen C. Rose, PhD, MS

Could removing a troublesome population of cells help a scarred liver recover? A small clinical trial published in Nature Metabolism on October 1, 2026 offers an encouraging early answer. People with an inflammatory form of fatty liver disease who received dasatinib plus quercetin were more likely than those receiving placebo to show improvement in liver biopsies. The findings warrant larger studies, but they do not establish a treatment for general aging or justify taking this drug combination independently. [1]

The study concerns metabolic dysfunction-associated steatohepatitis, or MASH, previously called NASH. In this condition, fat accumulation accompanies liver-cell injury and inflammation. Repeated injury can produce fibrosis, the buildup of scar tissue. More advanced disease can progress to cirrhosis, liver failure, or liver cancer, although not everyone follows that course. [2]

Why senescent cells are a target

Senescent cells have entered a state in which they largely stop dividing but remain biologically active. They are not simply all the older cells in an older person. Cellular damage and other stresses can trigger senescence, even before old age. Some senescent cells release inflammatory and tissue-remodeling signals that affect their neighbors. Their persistent accumulation may help sustain injury and scarring. [1]

Senescence also has useful roles, including restraining damaged cells from dividing and participating in wound repair. Its effects depend on the cell type and circumstances. The therapeutic goal is therefore selective removal of harmful populations, rather than indiscriminately eliminating every cell with a senescence marker. [1]

Drugs intended to eliminate senescent cells are called senolytics. Dasatinib is a prescription kinase inhibitor used for certain leukemias. Quercetin is a plant-derived flavonoid. Together, they can interfere with survival pathways on which some senescent cells depend. The combination remains investigational for MASH; quercetin's presence in foods does not make the experimental treatment equivalent to a dietary intervention. [1][3]

A 2025 study combined human tissue analyses with laboratory and mouse experiments to identify senescent liver-cell signatures and test potential treatments. Selected senolytics improved disease in male mice. That work supported the biological rationale, but animal results cannot establish human effectiveness. [4]

An earlier pilot study in nine people with diabetic kidney disease found reductions in senescence-associated markers in fat and skin after dasatinib plus quercetin. It had no placebo group and was not a liver-treatment trial. It provided preliminary evidence that the combination could affect relevant biology in humans, rather than proof of broad rejuvenation. [5]

What the new trial tested

Researchers at Amsterdam University Medical Center randomized 31 participants with biopsy-confirmed MASH and moderate-to-advanced fibrosis to dasatinib plus quercetin or matched placebo. Seventeen received active treatment and 14 received placebo. Participants and treating physicians were blinded to allocation. Treatment was intermittent over 21 weeks, with drug-free periods between courses. [1]

This was a selected clinical population whose liver function was still preserved, rather than healthy volunteers seeking younger biological-age scores. People with important contraindications or interacting medications were excluded. The study therefore cannot be generalized automatically to people with cirrhosis, significant other illnesses, or uncomplicated liver fat. [1]

The primary outcome was improvement by at least one fibrosis stage without worsening of MASH, measured by comparing liver biopsies taken before and after treatment. Three independent pathologists reviewed the samples while blinded to treatment and timing. This approach assessed tissue changes directly, beyond changes in a blood test. [1]

Eight of 17 treated participants, or 47%, met that primary outcome, compared with one of 14 placebo recipients, or 7%. MASH resolution was also more frequent: nine of 17 versus one of 14. These were separate outcomes; resolution of inflammatory disease did not mean that every trace of scarring had disappeared. [1]

Four participants lacked follow-up biopsies. The main analysis counted them as nonresponders, preserving the original randomized groups. Several sensitivity analyses supported the direction of benefit, but one conservative assumption about the missing results removed statistical significance. That makes replication especially important. [1]

What the tissue findings suggest

The researchers also examined gene activity in individual cell nuclei, the compartments containing DNA, from liver samples. Treatment was accompanied by lower senescence- and fibrosis-associated gene signatures and changes in cell populations involved in inflammation and scar formation. These observations support a plausible mechanism linking the treatment to the biopsy improvements. [1]

They do not prove that selective destruction of senescent cells was the sole cause. Dasatinib has other biological effects, including effects on blood-cell production and inflammatory pathways. Changes in gene signatures can also reflect changes in which cells are present or how they behave. The molecular results help generate explanations that future experiments must test. [1]

Several other measurements, including liver stiffness, common fibrosis blood tests, liver enzymes, and measures of insulin resistance, did not show statistically significant differences between groups. The biopsy findings should therefore not be expanded into claims that the treatment improved every aspect of metabolic health. [1]

Safety and unanswered questions

Adverse events were reported by 82% of the treatment group and 43% of the placebo group. Most were mild or moderate; one treated participant discontinued because of gastrointestinal complaints. Platelets, which help blood clot, were lower with treatment, although the trial reported no cases of myelosuppression, a substantial suppression of blood-cell production. [1]

Outside this small study, dasatinib can cause serious adverse effects and has important medication interactions. Its established cancer uses require medical supervision and laboratory monitoring. Short, intermittent exposure in carefully screened participants cannot demonstrate that long-term or unsupervised use is safe. [3]

The study was too small and brief to determine whether improvements last, reduce liver failure or cancer, or improve survival. Diabetes was also more common in the treatment group at baseline, illustrating the imbalances possible in small trials. No result establishes a reduction in biological age or an extension of human lifespan. The authors appropriately frame their findings as hypothesis-generating. [1]

How you may be able to benefit

The immediate opportunity is to assess and reduce established liver risks. If you have type 2 diabetes, obesity, or known fatty liver, ask whether assessment for fibrosis is appropriate. Clinical guidance supports an initial blood-based score such as FIB-4, followed when indicated by liver-stiffness testing. These tests require interpretation in context; they are not do-it-yourself diagnoses. [6]

For people with overweight and fatty liver disease, sustained weight reduction can help. Guidelines suggest about 5% weight loss to reduce liver fat, 7-10% to improve inflammation, and at least 10% for possible fibrosis improvement. These are treatment targets, not guaranteed individual results, and should be adapted to nutritional status and illness. A prospective lifestyle study linked greater weight loss to greater biopsy improvement, but it was not a randomized comparison. [6][7]

For eating, a Mediterranean-style pattern is a reasonable starting point: vegetables, legumes, whole grains, nuts, olive oil, and suitable fish or other protein sources. Reducing sugar-sweetened drinks and foods high in saturated fat is also supported. Regular activity can reduce liver fat, with exercise adapted to capacity. These recommendations come from broader liver-health evidence; the senolytic trial itself did not test or identify an ideal diet. [6][8]

Existing treatment options also deserve discussion. The FDA has approved resmetirom, sold as Rezdiffra, and semaglutide injection, sold as Wegovy, for eligible adults with noncirrhotic MASH and moderate-to-advanced fibrosis. Both received accelerated approval based on tissue outcomes, with further evidence needed to confirm clinical benefits. Eligibility, contraindications, and ongoing care matter. [9][10]

The new trial adds a promising research direction to that conversation. It suggests that targeting a process associated with aging might help a specific disease. For now, appropriate liver assessment, sustainable metabolic care, and informed discussion of available treatments have the clearest practical value. An improved liver biopsy alone cannot establish whole-body rejuvenation.

References

[1] Koning M, Kovynev A, Fondevila MF, et al. Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial. Nat Metab. Published online October 1, 2026. doi:10.1038/s42255-026-01643-4.

[2] National Institute of Diabetes and Digestive and Kidney Diseases. Definition & Facts of NAFLD & NASH. National Institutes of Health. Reviewed April 2021. Accessed October 5, 2026.

[3] MedlinePlus. Dasatinib. National Library of Medicine. Revised February 15, 2025. Accessed October 5, 2026.

[4] Du K, Umbaugh DS, Wang L, et al. Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction. Nat Commun. 2025;16(1):3038. doi:10.1038/s41467-025-57616-w.

[5] Hickson LJ, Langhi Prata LGP, Bobart SA, et al. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019;47:446-456. doi:10.1016/j.ebiom.2019.08.069.

[6] European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obes Facts. 2024;17(4):374-444. doi:10.1159/000539371.

[7] Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015;149(2):367-78.e5; quiz e14-5. doi:10.1053/j.gastro.2015.04.005.

[8] National Institute of Diabetes and Digestive and Kidney Diseases. Eating, Diet, & Nutrition for NAFLD & NASH. National Institutes of Health. Accessed October 5, 2026.

[9] U.S. Food and Drug Administration. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. March 14, 2024. Accessed October 5, 2026.

[10] U.S. Food and Drug Administration. FDA Approves Treatment for Serious Liver Disease Known as MASH. Accessed October 5, 2026.