Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease
Comprehensive Overview
Published in EBioMedicine in 2019, this study asked whether a combination of two existing drugs could directly clear aging, dysfunctional cells called senescent cells from human tissue, since these cells accumulate with age and disease and release harmful inflammatory signals, yet no prior published human trial had directly shown that any drug reduces their numbers in people. Researchers conducted a small, open-label Phase 1 pilot trial in nine adults, mostly older men, with diabetes and chronic kidney disease, giving each participant a three-day oral course of the cancer drug dasatinib plus the plant-derived compound quercetin, a drug pairing known as D plus Q. Eleven days after completing this brief treatment, researchers took new biopsies of abdominal fat tissue and skin and compared them with biopsies taken before treatment, counting cells expressing senescence markers such as p16 and p21, measuring a senescence-associated enzyme activity, and analyzing blood for inflammatory proteins these cells typically secrete. The topline result was that this short drug course meaningfully reduced the abundance of senescent cells in both fat and skin tissue and lowered several of the inflammatory blood markers these cells produce, despite the drugs themselves clearing from the body within about half a day.
Outcomes and Implications
The single most important finding was that eleven days after the three-day drug course, fat tissue biopsies showed substantially fewer senescent cells by every measure used, including reductions in cells expressing the aging markers p16 and p21 and in a senescence-associated enzyme activity, alongside fewer tissue macrophages and fewer inflammatory "crown-like" cell clusters that typically surround dying fat cells. Skin biopsies showed a parallel decline in senescent cells within the outer skin layer, and several inflammatory proteins these cells release into the bloodstream, part of what researchers call the senescence-associated secretory phenotype, were also measured at lower levels after treatment. Notably, fat-derived progenitor cells taken after treatment multiplied more readily in the laboratory than those taken before treatment, suggesting the tissue's capacity for healthy cell renewal had improved. Because dasatinib and quercetin themselves are cleared from the body within roughly half a day, yet their effects on senescent cell numbers persisted well beyond that window, the authors describe this as a "hit-and-run" mechanism, in which brief drug exposure permanently eliminates existing senescent cells without needing continuous dosing. As a small, uncontrolled pilot study in only nine participants, these findings need confirmation in larger, controlled trials before any clinical use is considered, but the authors argue this preliminary evidence supports testing whether senolytic drugs can broadly delay, prevent, or alleviate multiple age-related and diabetes-related diseases as a group, rather than developing separate treatments for each condition one at a time.