Ontology highlight
ABSTRACT:
PROVIDER: PRJNA642362 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12105004.fastq.gz | Fastqsanger.gz | |||
| SRR12105005.fastq.gz | Fastqsanger.gz | |||
| SRR12105006.fastq.gz | Fastqsanger.gz | |||
| SRR12105007.fastq.gz | Fastqsanger.gz | |||
| SRR12105008.fastq.gz | Fastqsanger.gz |
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Project description:A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction, and inflammation, which collectively contribute to age-related kidney disease. Here we studied the role of the nuclear hormone receptors, the estrogen related receptors (ERRs) in regulation of age-related mitochondrial dysfunction and inflammation. ERRs are decreased in aging human and mouse kidneys and preserved in aging mice with lifelong caloric restriction (CR). Our studies identified ERRs as important modulators of age-related mitochondrial dysfunction and inflammation. ERRα, ERRβ, and ERRγ levels are decreased in the aging kidney. Remarkably, only a 4-week treatment of 21-month-old mice with the pan ERR agonist reversed the age-related increases in albuminuria and podocyte loss, mitochondrial dysfunction and inflammatory cytokines, including the cGAS-STING and STAT3 signaling pathways. A 3-week treatment of 21-month-old mice with a STING inhibitor reversed the increases in inflammatory cytokines and the senescence marker p21 but also unexpectedly reversed the age-related decreases in PGC-1α, ERRα, mitochondrial complexes and Mcad expression.
2023-08-02 | PXD020051 | Pride
Project description:Background: A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction and inflammation, which collectively contribute to age-related kidney dysfunction and disease. Here we studied the role of the nuclear hormone receptors, the estrogen related receptors (ERRs) in regulation of age-related mitochondrial dysfunction and inflammation. Methods: ERRs were decreased in aging human and mouse kidneys and were preserved in aging mice with lifelong caloric restriction (CR). Pan-ERR agonist was used to treat 21-month-old mice for 8-weeks. Results: Remarkably, only an 8-week treatment with the pan-ERR agonist reversed the age-related increases in albuminuria and podocyte loss, mitochondrial dysfunction and inflammatory cytokines, including the cGAS-STING and STAT3 signaling pathways. A 3-week treatment of 21-month-old mice with a STING inhibitor reversed the increases in inflammatory cytokines and the senescence marker p21 but also unexpectedly reversed the age-related decreases in PGC-1α, ERRα, mitochondrial complexes and MCAD expression. Conclusions: Our studies identified ERRs as important modulators of age-related mitochondrial dysfunction and inflammation.
2020-07-09 | GSE154050 | 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:Sarcopenia, the age-related loss of skeletal muscle mass and function, can dramatically impinge on quality of life and mortality. While mitochondrial dysfunction and imbalanced proteostasis are recognized as hallmarks of sarcopenia, the regulatory and functional link between these processes is underappreciated and unresolved. We therefore investigated how mitochondrial proteostasis, a crucial process that coordinates the expression of nuclear- and mitochondrial-encoded mitochondrial proteins with supercomplex formation and respiratory activity, is affected in skeletal muscle aging. Intriguingly, a robust mitochondrial translation impairment was observed in sarcopenic muscle, which is regulated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) with the estrogen-related receptor alpha (ERRalpha). Exercise, a potent inducer of PGC-1alpha activity, rectifies age-related reduction in mitochondrial translation, in conjunction with quality control pathways. These results highlight the importance of mitochondrial proteostasis in muscle aging, and elucidate regulatory interactions that underlie the powerful benefits of physical activity in this context.
2023-06-05 | MSV000092099 | MassIVE
Project description:Metabolic abnormalities and mild inflammation are hallmarks of aging and major driving factors for aging-related damage and bone metabolic diseases. Mitochondria are crucial links in energy metabolism and immune homeostasis regulation. Mitochondrial dysfunction is considered one of the pathogenic factors of aging-related osteoporosis, but its mechanism of action needs further research. Here, we demonstrated that the interaction between stimulator of interferon genes (STING)-mediated regulation of hexokinase 2 (Hk2)-voltage-dependent anion channel-1 (Vdac1) is a critical factor contributing to mitochondrial dysfunction and osteogenic abnormalities during aging. As the aging process progresses, factors related to aging cause an increase in STING expression, which disrupts the interaction between Hk2 and Vdac1. Dissociation of Hk2 from Vadc1 triggered the opening of the mitochondrial inner mitochondrial permeability transition pore (mPTP), leading to mitochondrial dysfunction and abnormal osteogenic differentiation, thereby disrupting bone homeostasis. In brief, this study demonstrates that STING acts as an intracellular metabolic Checkpoint, influencing mitochondrial function to promote the development of osteoporosis. These findings significantly enhance the development of STING-targeted treatments for aging-related osteoporosis.
2025-07-05 | GSE301157 | GEO
Project description:Mitochondria take part in a network of intracellular processes that regulate homeostasis. Mitochondrial dysfunction is implied as a crucial factor in age-related chronic kidney disease. Gli-like transcription factor 1 (GLIS1) is enriched in physiology aging kidneys and decreased in aged human kidney that was confirmed in our previous research, however, the correlation between mitochondrial disturbances and GLIS1-driven kidney aging are not clearly clarified. Thus, we investigated the role of GLIS1 in the homeostasis of mitochondrial quality control both in vivo and in vitro. The lower expression of GLIS1 was identified in natural and accelerated aged models, accompanied by the mitochondrial quality control (MQC) dysfunctions, including enhanced mitochondrial fission, reduced mitochondrial biogenesis and mitophagy. After the induction of kidney aging, adeno-associated virus carrying GLIS1 over-expression or vector were delivered to the mice.
2024-12-09 | GSE237055 | GEO
Project description:Mitochondrial fusion and fission proteins regulate mitochondrial quality control and mitochondrial metabolism. In turn, mitochondrial dysfunction is associated with aging, although its causes are still under debate. Here, we show that aging is characterized by a progressive reduction of Mitofusin 2 (Mfn2) in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, muscle Mfn2-deficient mice show unhealthy aging characterized by altered metabolic homeostasis and sarcopenia. Mfn2 deficiency impairs mitochondrial quality control, which contributes to an exacerbated age-related mitochondrial dysfunction. Surprisingly, aging-induced Mfn2 deficiency triggers a ROS-dependent retrograde signaling pathway through induction of HIF1 transcription factor and BNIP3. This pathway ameliorates mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that repression of Mfn2 in skeletal muscle during aging is determinant for the loss of mitochondrial quality, contributing to age-associated metabolic alterations and loss of muscle fitness. Quadriceps muscle from four mice per genotype were used (Control young (6 month-old), Mfn2KO young (6-month-old), control old (22-month-old) and Mfn2KO old (22-month-old)
2016-08-08 | E-GEOD-71501 | biostudies-arrayexpress
Project description:Here we show that estrogen-related receptor γ (ERRγ) is an essential transcriptional coordinator of both renal mitochondrial and reabsorptive functions. ERRγ is highly and specifically expressed in the RECs, and its expression correlates with kidney function in humans. We generated REC-ERRγ KO mice which developed severe renal mitochondrial and reabsorptive dysfunction and fluid-filled cysts. Transcriptome and cistrome analysis revealed that ERRγ directly regulates mitochondrial metabolism and renal reabsorption. ChIP-reChIP-Seq studies further suggest that ERRγ employs a distinct mechanism to regulate renal reabsorption genes through functional cooperation with hepatic nuclear factor 1 beta (HNF1β), mutations of which cause strikingly similar renal dysfunction and cysts in humans and animals. Together these findings reveal a novel role for ERRγ in simultaneously coordinating a transcriptional program for renal energy production via mitochondria and energy consumption to perform reabsorptive functions required for normal kidney function
2018-04-25 | GSE104906 | GEO
Project description:Here we show that estrogen-related receptor γ (ERRγ) is an essential transcriptional coordinator of both renal mitochondrial and reabsorptive functions. ERRγ is highly and specifically expressed in the RECs, and its expression correlates with kidney function in humans. We generated REC-ERRγ KO mice which developed severe renal mitochondrial and reabsorptive dysfunction and fluid-filled cysts. Transcriptome and cistrome analysis revealed that ERRγ directly regulates mitochondrial metabolism and renal reabsorption. ChIP-reChIP-Seq studies further suggest that ERRγ employs a distinct mechanism to regulate renal reabsorption genes through functional cooperation with hepatic nuclear factor 1 beta (HNF1β), mutations of which cause strikingly similar renal dysfunction and cysts in humans and animals. Together these findings reveal a novel role for ERRγ in simultaneously coordinating a transcriptional program for renal energy production via mitochondria and energy consumption to perform reabsorptive functions required for normal kidney function
2018-04-25 | GSE104905 | GEO
Project description:Cancer incidence increases in the elderly, although the underlying reasons for this association are unknown. We show that B-progenitors in old mice exhibit profound signaling and metabolic defects, and that expression of BCR-ABL, NRASV12 and MYC reverses these fitness defects, leading to selection of oncogenically-initiated cells and leukemogenesis in old hematopoietic backgrounds. Aging is associated with increased inflammation in the BM microenvironment, and inducing inflammation in young mice phenocopies aging B-lymphopoiesis. Importantly, reducing inflammation in aged mice preserves the function of B-progenitors and prevents NRasV12-mediated oncogenesis. We conclude that chronic microenvironments in old age lead to reductions in the fitness of hematopoietic stem and progenitor cell populations. This reduced progenitor pool fitness leads to selection for cells harboring oncogenic mutations in part due to their ability to correct aging-associated functional defects. Aging B-lymphopoiesis is accompanied by significant reductions in purine and pyrimidine metabolism. Microarray experiment results also indicated that mitochondrial dysfunction accompanied aging B-lymphopoiesis.
2015-10-15 | GSE67827 | GEO