Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice
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ABSTRACT:
PROVIDER: PRJNA408136 | ENA |
REPOSITORIES: ENA
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Project description:Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study gut microbiota from young or old conventional mice was transferred to young germ-free mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer’s patches, and mesenteric lymph nodes from conventionalized germ-free mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here we show by transferring aged microbiota to young germ-free mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the germ-free mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young germ-free mice.
2018-02-14 | GSE104063 | GEO
Project description: Not available
| S-EPMC5674680 | biostudies-literature
Project description:Low-grade chronic inflammation is considered a hallmark of ageing and associated with impaired tissue function and development of disease. However, how cell-intrinsic and -extrinsic factors interact to establish this phenotype, termed inflammaging, remains poorly understood. We addressed this question in the mouse intestinal epithelium, using organoid cultures to dissect stem cell-intrinsic and -extrinsic sources of increased inflammatory signaling upon ageing. At the single-cell level, we found that inflammaging establishes differently in cells along the crypt-villus axis, including intestinal stem cells (ISCs). Importantly, the inflammaging phenotype was stably propagated by aged ISCs in organoid cultures and associated with increased chromatin accessibility of inflammation-associated loci in vivo and ex vivo, indicating a cell-intrinsic memory of inflammation. Mechanistically, we show that expression of inflammaging genes is dependent on STAT1 signaling. Together, our data reveal that inflammaging in the intestine is promoted by a cell-intrinsic mechanism, stably propagated by ISCs and associated with a disbalance in immune homeostasis.
2023-10-26 | GSE233898 | GEO
Project description:Low-grade chronic inflammation is considered a hallmark of ageing and associated with impaired tissue function and development of disease. However, how cell-intrinsic and -extrinsic factors interact to establish this phenotype, termed inflammaging, remains poorly understood. We addressed this question in the mouse intestinal epithelium, using organoid cultures to dissect stem cell-intrinsic and -extrinsic sources of increased inflammatory signaling upon ageing. At the single-cell level, we found that inflammaging establishes differently in cells along the crypt-villus axis, including intestinal stem cells (ISCs). Importantly, the inflammaging phenotype was stably propagated by aged ISCs in organoid cultures and associated with increased chromatin accessibility of inflammation-associated loci in vivo and ex vivo, indicating a cell-intrinsic memory of inflammation. Mechanistically, we show that expression of inflammaging genes is dependent on STAT1 signaling. Together, our data reveal that inflammaging in the intestine is promoted by a cell-intrinsic mechanism, stably propagated by ISCs and associated with a disbalance in immune homeostasis.
2023-10-26 | GSE233899 | GEO
Project description:To begin to explore mechanisms by which microbiota signals regulate HSC lineage bias, gene expression profiling was performed on sorted LSK-SLAM cells from aged SPF and aged GF mice.
2021-11-10 | GSE183138 | GEO
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
Project description:Aging is accompanied by chronic, low-grade systemic inflammation, termed inflammaging, a main driver of age-associated diseases. Such sterile inflammation is typically characterized by elevated levels of pro-inflammatory mediators, such as cytokines and reactive oxygen species causing organ damage. Lipid mediators play important roles in the fine-tuning of both the promotion and the resolution of inflammation. Yet, it remains unclear how lipid mediators fit within the concept of inflammaging and how their biosynthesis and function is affected by aging. Here, we provide comprehensive signature profiles of inflammatory markers in organs afflicted with inflammation of young and old C57BL/6 mice. We reveal an organ-specific footprint of inflammation-related cytokines, chemokines and lipid mediators, which are distinctively affected by aging. While some organs are characterized by a pronounced pro-inflammatory microenvironment and impaired resolution during aging, others display elevated levels of pro-resolving mediators or an overall decrease in inflammatory signaling. Our results demonstrate that it proves difficult to establish a unifying concept for alterations of immunomodulatory mediators as consequence of aging and that organ specificity needs to be considered. Moreover, our data imply that inclusion of lipid mediators into the concept of inflammaging provides a comprehensive tool to characterize the inflammatory microenvironment during aging on a broader and yet, more detailed scope.
2021-03-22 | PXD024356 | Pride
Project description:Sorted HSCs from aged Specific Pathogen Free and germ free mice
| PRJNA759251 | ENA
Project description:Aging is associated with systemic chronic inflammation (inflammaging) that leads to impaired physiological functions and vulnerability to several diseases. However, underlying alterations in aged immune system resulting in gradual loss of immune fitness remain unclear. Using a combination of CD8 T cell transfer from young to old and from old to young mice and single-cell RNA sequencing, we characterized the age-associated alterations in CD8 T cells. We transferred 2 millions of purified CD8+ T cells pooled from 3 CD45.1 C57BL/6J 3 months old female mice (donor) by i.v. injection into CD45.2 C57BL/6J 24 months old female mouse (recipient) and sorted CD45.1+CD3e+CD8a+ and CD45.2+CD3e+CD8a+ T cells from the spleen 1 month post transfer to perform scRNA/TCR-seq.
2020-12-06 | GSE155005 | GEO
Project description:Human (healthy control and CRC donors) fecal microbiota transfer (FMT) to germ-free mice.
| PRJEB35144 | ENA