PXD045573-1

PXD045573 is an original dataset announced via ProteomeXchange.

Title	Altered protein cysteine reactivity in senescent cells is a vulnerability for senolysis to ameliorate aging
Description	Diet profoundly shapes human physiology and health, including aging and age-related diseases marked by senescent cell accumulation. However, the underlying mechanisms remain unclear. Here, we report vanadyl sulfate (VS), a mineral dietary supplement, as a senolytic agent. Oral VS extends lifespan and ameliorates phenotypes of aging and diverse age-related disorders. Integrated functional-omics analyses show that senescent cells exhibit globally reduced proteome cysteine reactivity, but upregulated expression of proteins essential for endoplasmic reticulum (ER) proteostasis, accompanied by increased apparent cysteine reactivity. This redox-proteostasis state is linked to glutathione disulfide (GSSG) accumulation that can be recapitulated by GSSG delivery in non-senescent cells. Mechanistically, VS inactivates reactive cysteines and promotes disulfide bond formation in senescent cells, leading to protein misfolding, aggregation and ultimately cell death. Glutathione reductase (GSR) downregulation promotes GSSG accumulation, distinguishing senescent from non-senescent cells and conferring selective susceptibility to VS. Our findings reveal an exploitable redox-proteostasis vulnerability of senescent cells with therapeutic potential to ameliorate aging.
HostingRepository	PRIDE
AnnounceDate	2026-09-04
AnnouncementXML	Submission_2026-09-04_01:47:19.027.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fan Yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	biotinylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-21 15:31:47	ID requested
⏵ 1	2026-09-04 01:47:19	announced

Dataset with its publication pending

submitter keyword: senolysis, Cysteine,Vanadyl sulfate

Jing Chen
contact affiliation	1Department of Medicine, The University of Chicago
contact email	jingchen@uchicago.edu
lab head
Fan Yang
contact affiliation	University of Chicago
contact email	fanyang22@uchicago.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045573
     1. Label: PRIDE project
     2. Name: Altered protein cysteine reactivity in senescent cells is a vulnerability for senolysis to ameliorate aging