Senolytic Treatment with Dasatinib and Quercetin Rejuvenates the Aging Kidney in Mice
There is a large body of evidence in animal studies to show that treatment with dasatinib and quercetin clears a fraction of the lingering senescent cells present in tissues throughout the body to restore more youthful function to many different organs and systems. Today's open access paper, focused on kidney rejuvenation via removal of senescent cells, is yet another to add to the scores of existing studies. Dasatinib is a generic chemotherapeutic drug, while quercetin is a plant flavonol; both cost little. Dasatinib can be readily obtained these days via anti-aging clinical practices, offshore pharmacies, and the other usual approaches to access low cost prescription drugs. Quercetin can be found in any supplement store.
Sadly, exactly because dasatinib and quercetin are cheap compounds, there is very little incentive for anyone to fund the sizable expense of running large clinical trials to first establish optimal dosing, and secondly confirm that this treatment is as good for aged humans as it is for aged mice. Those trials that have taken place were funded by academic institutions, were small, exploratory, and the results were promising. Only larger trials can move from promising to "yes, this works," however. Meanwhile, any older person willing to put in the effort can run their own study of one, and see how a range of biomarkers look before and after treatment. The human trials suggest that side-effects for a short course of treatment are minimal compared to potential benefits.
Multi-omics profiling reveals systemic rejuvenation of the aged kidney through senolytic therapy
Cellular senescence is a key driver of kidney aging, leading to functional decline and increased susceptibility to chronic kidney disease. While the senolytic combination of dasatinib and quercetin (D + Q) has shown promise in mitigating age-related pathologies, its long-term effects and underlying multi-level systemic mechanisms in the aging kidney remain poorly defined. Here, we systematically evaluated the long-term effects of D + Q in naturally aged mice using multi-omics approaches. Beginning at 12 months of age, mice assigned to the treatment arm received biweekly oral gavage of the D + Q cocktail for a total duration of 8 months.
We show that D + Q treatment reduces senescence markers (p16, p21, SA-β-gal), restores the anti-aging protein Klotho, and attenuates renal fibrosis and inflammation. Proteomic profiling reveals that D + Q enhances apoptotic clearance of senescent cells and promotes proliferative and regenerative pathways. Moreover, D + Q reactivates PPARα signaling, improves fatty acid oxidation, and reduces lipid accumulation in aged kidneys. Single-cell transcriptomics further demonstrates that D + Q reverses transcriptional aging signatures across multiple renal cell types and remodels cell-type-specific pathways associated with metabolism, inflammation, and fibrosis. Cell-cell communication analysis reveals that D + Q normalizes the hyperconnected intercellular network in aged kidneys, particularly by modulating inflammation-related signaling.
Our findings offer a comprehensive, systems-level understanding of how senolytic therapy restores renal homeostasis, emphasizing its potential as a multifaceted intervention to combat kidney aging.