Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Persistent ER stress in macrophages fuels age-related inflammation and vulnerability to infection

ABSTRACT: Aging is accompanied by a state of chronic, low-grade inflammation known as inflammaging that underlies increased susceptibility to infection and many age-related pathologies. Although macrophages are central to immune regulation and inflammation, the molecular mechanisms driving their age-associated dysfunction remain incompletely defined. Here, we performed bulk RNA-sequencing on FACS-sorted peritoneal macrophages from young and aged mice. Analysis of differentially expressed genes revealed that genes upregulated in aged macrophages were significantly enriched for pathways related to "response to interferon-beta" and "response to interferon-gamma". Further investigation of our RNA-seq data for upstream mediators of these genes showed that Stat1 was markedly upregulated in aged macrophages. These transcriptomic findings suggest that the chronic activation of ER UPR in aged macrophages drives an enhanced ISG program, representing a potential mechanism for inflammaging.

ORGANISM(S): Mus musculus

PROVIDER: GSE304706 | GEO | 2026/08/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease [NAFLD_time_course]

Project description:Cellular senescence drives chronic sterile inflammation during aging via the senescence-associated secretory phenotype (SASP); however, the cell types responsible for this pathology remain poorly defined. Here, we identify p21⁺Trem2⁺ senescent macrophages as a major source of inflammaging. Using primary mouse and human macrophages, we developed a model of DNA damage and cholesterol-induced senescence and applied multi-omic profiling to fully characterize senescent macrophages. We found that senescent macrophages exhibit a distinctive p21-TREM2 expression profile and SASP, driven in part by type-I interferon signaling via secreted mitochondrial DNA. We also found that senescent macrophage accumulation occurs in aged and MASLD mouse livers and is enriched in human cirrhotic liver tissue. Finally, senolytic treatment targeting senescent macrophages reduced liver inflammation and steatosis in both aged and MASLD mice. Together, these findings establish macrophage senescence as a central driver of chronic inflammation in aging and metabolic liver disease, highlighting a promising, tractable therapeutic target.

2026-02-16 | GSE319035 | GEO

P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease. [Blood]

2026-02-11 | GSE318806 | GEO

P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease. [macro_senescence]

2026-02-11 | GSE318804 | GEO

P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease. [Trem2ko]

2026-02-11 | GSE318802 | GEO

P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease.

2026-02-11 | GSE318801 | GEO

P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease [RNAseq_sgCMPK2]

2026-02-10 | GSE318651 | GEO

P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease [RNAseq_MASHABT263]

2026-02-10 | GSE318652 | GEO

Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation

Project description:Age-related inflammation or ‘inflammaging’ is a key mechanism that increases disease burden and may control lifespan. How adipose tissue macrophages (ATMs) control inflammaging is not well understood in part because the molecular identities of niche-specific ATMs are incompletely known. Using intravascular labeling to exclude circulating myeloid cells and subsequent single-cell sequencing with orthogonal validation, we define the diversity and alterations in niche resident ATMs through lifespan. Aging led to depletion of vessel-associated macrophages (VAMs), expansion of lipid-associated macrophages (LAMs), and emergence of a unique subset of CD38+ age-associated macrophages (AAMs) in visceral white adipose tissue (VAT). Interestingly, CD169+CD11c- ATMs are enriched in a subpopulation of nerve-associated macrophages (NAMs) that declines with age. Depletion of CD169+ NAMs in aged mice increases inflammaging and impairs lipolysis suggesting that they are necessary for preventing catecholamine resistance in VAT. These findings reveal specialized ATMs control adipose homeostasis and link inflammation to tissue dysfunction during aging.

2025-06-23 | GSE294122 | GEO

P21 plus Senescent Macrophages Fuel Inflammation and Disease in Aging and Metabolic Dysfunction-Associated Steatotic Liver Disease

Project 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

2025-05-30 | MSV000098058 | MassIVE

AP-1 is a regulatory transcription factor of inflammaging in the murine kidney and liver

Project description:Aging is characterized by a chronic low-grade inflammation in multiple tissues, also termed as “inflammaging”, which represents a significant risk factor for many aging-related chronic diseases. However, the mechanisms and regulatory networks behind inflammaging across different tissues have not been fully elucidated. Here, by profiling transcriptomes and epigenomes of the kidney and liver from young and aged mice, we found that activation of inflammatory response was the conserved signature across tissues. Through integrative analysis, we revealed links between transcriptome change and chromatin dynamics, and identified AP-1 and ETS family transcription factors (TFs) were potential regulators of inflammaging. Further in-situ validation showed AP-1 was mainly activated in aged hepatic and renal cells, while enhanced ETS was almost caused by elevated infiltration of macrophages, indicating these TFs had different mechanisms in inflammaging. Functional data showed genetic knockdown of Fos, a major member of AP-1, significantly attenuated inflammatory response in aged kidneys and livers. Taken together, our analysis revealed conserved signatures and regulatory TFs of inflammaging in the kidney and liver, providing novel targets for the development of anti-aging interventions.

2022-12-30 | GSE221801 | GEO