PXD076057-1

PXD076057 is an original dataset announced via ProteomeXchange.

Title	Multi-omics profiling reveals systemic rejuvenation of the aged kidney through senolytic therapy
Description	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. 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.
HostingRepository	iProX
AnnounceDate	2026-03-24
AnnouncementXML	Submission_2026-09-09_23:54:17.377.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yaohui He
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-23 23:57:25	ID requested
⏵ 1	2026-09-09 23:54:18	announced

Chen S, Zhang C, Cang P, Guo W, Xiao L, He Y, Su Q, Ouyang S, Zha J, Maimaitirexiati G, Chen Y, Qi X, He S, Zhang Q, Xu Y, Yang J, Fan G, Multi-omics profiling reveals systemic rejuvenation of the aged kidney through senolytic therapy. NPJ Regen Med, 11(1):(2026) [pubmed]

submitter keyword: Renal aging, senolytics, inflammation, multi-omics, intercellular communication

Yaohui He
contact affiliation	University of South China
contact email	2024001050@usc.edu.cn
lab head
Yaohui He
contact affiliation	University of South China
contact email	969220692@qq.com
dataset submitter

iProX dataset URI