Aging and senescence-associated signatures of aged kidney glomerular cells
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ABSTRACT:
PROVIDER: PRJNA1003456 | ENA |
REPOSITORIES: ENA
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Project description:The kidney governs many physiological factors of the body, and the glomerulus is its core filtration unit. Glomeruli comprise of less than 1.5% of the kidney’s volume and thus are underrepresented in many analyses of the kidney, and require particular isolation methods. Aging is a major risk factor for kidney disease, yet despite the importance of proper glomerular function, we have limited knowledge of the changes that glomerular cells undergo during aging. Here we interrogate the aged mouse kidney, glomerulus and glomerular cells using various approaches, including single cell RNA sequencing (scRNA-Seq), to identify age and senescence associated changes at the tissue and cellular level. We show that the aged kidney and glomerulus undergo structural changes, including increased fibrosis, glomerulonephritis and expression of injury and senescence-associated markers. Lastly, we utilized our method for high-throughput analysis of mouse glomeruli to characterize cell-specific and age-related changes in glomerular cells. This analysis revealed a senescence-associated phenotype in aged mesangial cells, and emphasized the potential importance of mesangial cells and macrophages in this niche. Our study provides insights into the molecular and cellular changes of the aging glomerulus that suggest therapeutic targets for age-related renal dysfunction.
2024-09-01 | GSE240374 | GEO
Project description:The kidney governs many physiological factors of the body, and the glomerulus is its core filtration unit. Glomeruli comprise of less than 1.5% of the kidney’s volume and thus are underrepresented in many analyses of the kidney, and require particular isolation methods. Aging is a major risk factor for kidney disease, yet despite the importance of proper glomerular function, we have limited knowledge of the changes that glomerular cells undergo during aging. Here we interrogate the aged mouse kidney, glomerulus and glomerular cells using various approaches, including single cell RNA sequencing (scRNA-Seq), to identify age and senescence associated changes at the tissue and cellular level. We show that the aged kidney and glomerulus undergo structural changes, including increased fibrosis, glomerulonephritis and expression of injury and senescence-associated markers. Lastly, we utilized our method for high-throughput analysis of mouse glomeruli to characterize cell-specific and age-related changes in glomerular cells. This analysis revealed a senescence-associated phenotype in aged mesangial cells, and emphasized the potential importance of mesangial cells and macrophages in this niche. Our study provides insights into the molecular and cellular changes of the aging glomerulus that suggest therapeutic targets for age-related renal dysfunction.
2024-09-01 | GSE240373 | GEO
Project description:Aging and senescence-associated signatures of aged kidney glomerular cells [scRNA-seq]
| PRJNA1003460 | ENA
Project description:Aging and senescence-associated signatures of aged kidney glomerular cells [bulk RNA-seq]
| PRJNA1003459 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-09-01 | GSE240375 | GEO
Project description:Kidney is a vital organ responsible for homeostasis in the body. To retard kidney aging is of great importance for maintaining body health. Whereas the therapeutic strategies targeting against kidney aging are not elucidated. Recent studies show mitochondrial dysfunction is critical for renal tubular cell senescence and kidney aging, however, the underlying mechanisms of mitochondrial dysfunction in kidney aging have not been demonstrated. Herein, we found calcium overload, and the mitochondrial calcium uniporter (MCU) was induced in renal tubular cells and aged kidney. To activate MCU not only triggered mitochondrial calcium overload, but also induced reactive oxygen species (ROS) production and cellular senescence and age-related kidney fibrosis. Inversely, to block MCU or chelate calcium diminished ROS generation, restored mitochondrial homeostasis, and retarded cell senescence and protected against kidney aging. These results demonstrate MCU plays a key role in promote renal tubular cell senescence, which provides a new insight on the therapeutic strategy for fighting against kidney aging.
2024-10-02 | GSE262514 | GEO
Project description:Aging is a risk factor of carcinogenesis in various organs, and abnormal aging of the stem cells is considered responsible for carcinogenesis. Recent advances in organoid culturing system have made it viable to investigate mini organs developed from tissue stem cells. In this study, we aimed to investigate the implications of aging stem cells for gastric carcinogenesis. We found that gastric organoids of aged mice grew larger in size and proliferated vigorously compared to that of young mice. To elucidate the mechanism involved in this difference, we extracted the total RNA from the organoids and subjected it to microarray analysis, which revealed that the expression of transcription factor T-box 3 (Tbx3) was enhanced in aged gastric organoids. Further studies showed that this enhanced Tbx3 expression suppressed cellular senescence and enhanced proliferation. We utilized microarray analysis to find out the gene responsible for restraining cellular senescence in aged gastric organoids.
2023-03-22 | GSE185680 | GEO
Project description:The decrease in the podocyte’s lifespan and health-span that typify healthy kidney aging cause a decrease in their normal structure, physiology and function. The ability to halt and even reverse these changes becomes clinically relevant when disease is superimposed on an aged kidney. RNA-sequencing of podocytes from middle-aged mice showed an inflammatory phenotype with increases in the NLRP3 inflammasome, signaling for IL2/Stat5, IL6 and TNF, interferon gamma response, allograft rejection and complement, consistent with inflammaging. Furthermore, injury-induced NLRP3 signaling in podocytes was further augmented in aged mice compared to young ones. The NLRP3 inflammasome (NLRP3, Caspase-1, IL1ß IL-18) was also increased in podocytes of middle-aged humans. Higher transcript expression for NLRP3 in human glomerular was accompanied by reduced podocyte density and increased global glomerulosclerosis and glomerular volume. Pharmacological inhibition of NLRP3 with MCC950, or gene deletion, reduced podocyte senescence and the genes typifying aging in middle-aged mice, which was accompanied by an improved podocyte lifespan and health-span. Moreover, modeling the injury-dependent increase in NLRP3 signaling in human kidney organoids confirmed the anti-senescence effect of MC9950. Finally, the impact of NLRP3 also impacted liver aging. Together, these results suggest a critical role for the NLRP3 inflammasome in podocyte and liver aging.
2023-08-01 | GSE226796 | GEO
Project description:Normal aging is accompanied by escalating systemic inflammation. To comprehensively characterize the impact of aging on immune cells in the brain and periphery, we harvested immune cells from mouse spleen and brain tissues. Single cell sequencing was performed to compare the genetic signatures in these isolated immune cell subsets from spleen and brain tissues in young and aged mice. Our results demonstrate increased accumulations of immune cells such as natural killer (NK) cells in the aged brain as compared to the young brain. In addition, NK cells in the aged brain display augmented proliferation activity and cytotoxicity. RNA-sequencing of neuroblasts isolated from the aged brain revealed that aging induces dysregulated expression of genes related to DNA damage response and upregulation of senescence signatures.
2020-09-11 | GSE157771 | GEO
Project description:Normal aging is accompanied by escalating systemic inflammation. To comprehensively characterize the impact of aging on immune cells in the brain and periphery, we harvested immune cells from mouse spleen and brain tissues. Single cell sequencing was performed to compare the genetic signatures in these isolated immune cell subsets from spleen and brain tissues in young and aged mice. Our results demonstrate increased accumulations of immune cells such as natural killer (NK) cells in the aged brain as compared to the young brain. In addition, NK cells in the aged brain display augmented proliferation activity and cytotoxicity. RNA-sequencing of neuroblasts isolated from the aged brain revealed that aging induces dysregulated expression of genes related to DNA damage response and upregulation of senescence signatures.
2020-09-11 | GSE157770 | GEO