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PXD064467
PXD064467 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | P21 plus Senescent Macrophages Fuel Inflammation and Disease in Aging and Metabolic Dysfunction-Associated Steatotic Liver Disease |
| Description | DNA damage or other cellular stress can lead to an irreversible cell cycle arrest, known as cellular senescence. While cellular senescence can be beneficial in some contexts such as wound healing and development, it is now recognized as a major source of sterile inflammation in aging tissues via the secretion of inflammatory factors known as the senescence-associated secretory phenotype (SASP). Targeting senescent cells is therefore an emerging strategy for treating age-related diseases, however, the identity and function of specific senescent cell types remain unclear. Here, we identify p21 plus senescent macrophages as a key source of chronic inflammation in aging and MASLD. To further investigate macrophage senescence, we developed an in vitro model of DNA damage-induced macrophage senescence, using primary mouse and human macrophages, which we leveraged to identify unique biomarkers that distinguish senescent macrophages from other established polarized states. We show that DNA damage or excess cholesterol induces stable macrophage senescence marked by an elevated SASP, mitochondrial dysfunction, and interferon signaling. These senescent macrophages accumulate in aged mouse livers, particularly in Kupffer cells, and are enriched in human cirrhotic liver tissue. Using transcriptomic profiling we identified a unique MSen signature to identify macrophage senescence both in vitro and in vivo in both mice and humans. We also showed that senescent macrophages can be selectively targeted for depletion using the senolytic ABT-263 (Navitoclax), which reduces liver steatosis and inflammation in MASLD models, highlighting macrophage senescence as a major source of inflammaging and promising therapeutic target in age-related diseases |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-01-27 |
| AnnouncementXML | Submission_2026-01-27_09:01:57.236.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Christina King |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | TripleTOF 6600 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-05-30 20:55:00 | ID requested | |
| ⏵ 1 | 2026-01-27 09:01:57 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: senescence, macrophages, DIA-MS, secretome, SASP, DatasetType:Proteomics |
Contact List
| Birgit Schilling | |
|---|---|
| contact affiliation | Buck Institute |
| contact email | bschilling@buckinstitute.org |
| lab head | |
| Christina King | |
| contact affiliation | Buck Institute for Research on Aging |
| contact email | cking@buckinstitute.org |
| dataset submitter | |
Full Dataset Link List
| 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-ftp.ucsd.edu/v10/MSV000098058/ |
