Multi-omics profiling reveals systemic rejuvenation of the aged kidney through senolytic therapy

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.

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.