PXD034505-1

PXD034505 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	TXNRD1 drives innate immune response in senescent cells and promotes age-associated inflammation
Description	Sterile inflammation, also known as inflammaging, is a hallmark of tissue ageing. Cellular senescence contributes to tissue aging in part through secretion of proinflammatory factors known as senescence-associated secretory phenotype (SASP). Thioredoxin reductase 1 (TXNRD1) genetic variability is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living, and physical performance at old age. TXNRD1 role in regulating tissue ageing has been attributed to its enzymatic role in regulating cellular redox. Here we show that TXNRD1 drives SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune response pathway independently of its enzymatic activity. TXNRD1 localizes to cytoplasmic chromatin fragment and interacts with cGAS in a senescence status dependent manner. TXNRD1 enhances the enzymatic activity of cGAS. TXNRD1 and its interaction with cGAS is necessary for the SASP. TXNRD1 is required for both the tumor-promoting and immune-surveillance functions of senescent cells, which are mediated by SASP in vivo in mouse models. Treatment of aged mice with an TXNRD1 inhibitor that disrupts its interaction with cGAS, but not an inhibitor of its enzymatic activity, downregulated inflammaging in several tissues. In summary, our results report TXNRD1 promotes inflammaging via the innate immune response. They indicate that TXNRD1 and cGAS interaction is a relevant target for selectively suppressing inflammaging.
HostingRepository	MassIVE
AnnounceDate	2023-12-19
AnnouncementXML	Submission_2023-12-19_09:50:07.524.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hsin-Yao Tang
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive Plus

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-14 07:44:44	ID requested
⏵ 1	2023-12-19 09:50:07	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: inflammaging, senescence-associated secretory phenotype, TXNRD1

submitter keyword: inflammaging, senescence-associated secretory phenotype, TXNRD1

Contact List

Rugang Zhang
contact affiliation	The Wistar Institute
contact email	rzhang@wistar.org
lab head
Hsin-Yao Tang
contact affiliation	The Wistar Institute
contact email	tangh@wistar.org
dataset submitter

Full Dataset Link List

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MassIVE dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000089650/