Single-cell RNA-Seq of young, old and metformin-treated mouse muscle and adipose
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA800406 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17747969_1.fastq.gz | Fastqsanger.gz | |||
| SRR17747969_2.fastq.gz | Fastqsanger.gz | |||
| SRR17747970_1.fastq.gz | Fastqsanger.gz | |||
| SRR17747970_2.fastq.gz | Fastqsanger.gz | |||
| SRR17747971_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Here we investigate the nature of cellular heterogeneity in the gene expression of aging and characterize the changes that metformin causes in mouse adipose and muscle at the single-cell resolution. The single cell transcriptomes of ~13,000 cells were captured using single-cell RNA-sequencing, resulting in gene expression data for 13 cell types from the visceral adipose tissue stromal-vascular fraction and ~5,000 cells from 12 cell types from the gastrocnemius muscle. The study design featured three groups of male C57BL/6J mice that corresponded to three-month-old controls (young), 18-month-old controls (old), and 18-month-olds treated with 1000 ppm (0.1% w/w) metformin for 6 weeks (treated). Our analyses demonstrate that metformin’s age-associated changes results in the modulation of an old to young expression profile via a cell type-specific manner. This reversion is demonstrated by significant changes observed in cell-type proportions and the degree of cell-cell heterogeneity. Additionally, metformin is known to restore the dysregulation due to age in autophagy and immune response in adipose, hypoxia in muscle, and inflammatory responses in both tissues. In our data, we detect evidence of these processes at play where endothelial cells, macrophages, and stem/progenitor cells respond most effectively to metformin’s gerotherapeutic response compared to other cell types. We further characterize metformin’s role in reverting age-associated cell-type-specific shifts in the transcriptional space by investigating changes in gene expression distributions and gene regulatory network dynamics.
2022-11-07 | GSE194386 | GEO
Project description:Administration of metformin increases healthspan and lifespan in model systems and evidence from clinical trials and observational studies suggests that metformin delays a variety of age-related morbidities. Although metformin has been shown to modulate multiple biological pathways at the cellular level, these pleiotropic effects of metformin on the biology of human aging have not been studied. We studied ~70-year-old participants (n=14), in a randomized, double-blind, placebo-controlled, crossover trial in which they were treated with 6 weeks each of metformin and placebo. Following each treatment period, skeletal muscle and subcutaneous adipose tissue biopsies were obtained, and a mixed-meal challenge test was performed. As expected, metformin therapy lowered 2-hour glucose, insulin AUC, and insulin secretion compared to placebo. Using FDR<0.05, 647 genes were differentially expressed in muscle and 146 genes were differentially expressed in adipose tissue. Both metabolic and non-metabolic pathways were significantly influenced, including pyruvate metabolism and DNA repair in muscle and PPAR & SREBP signaling, mitochondrial fatty acid oxidation and collagen trimerization in adipose. While each tissue had, a signature reflecting its own function, we identified a cascade of predictive upstream transcriptional regulators, including mTORC1, MYC, TNF, TGFß1 and miRNA-29b, that may explain tissue-specific transcriptomic changes in response to metformin treatment. This study provides the first evidence that, in older adults, metformin has metabolic and non-metabolic effects linked to aging. These data can inform the development of biomarkers for the effects of metformin, and potentially other drugs, on key aging pathways. Key words: Aging, biguanides, gene expression, metabolism, upstream regulators
2017-12-12 | GSE107894 | GEO
Project description:Proteomics of young and old skeletal muscle tissue in cynomolgus monkeys
| PXD052984 |
Project description:Sarcopenic muscles exhibit reduced EV secretion and altered EV cargoes, promoting cancer progression. Her we performed miRNA-seq of exosomes secreted by young muscle (12-week-old NOD/SCID mouse) and old muscle (>12 month old NOD/SCID old mouse) to identify miRNAs that are potentially involved in this process.
2025-12-18 | GSE298395 | GEO
Project description:Fasting-refeeding paradigms result in drastic shifts in metabolism and gene expression patterns. The effect of fasting-refeeding changes between young and old individuals. We sought to decipher the changes in response to fasting-refeeding in young and old animals by profiling gene expression in adipose tissue of killifish Nothobranchius furzeri.
2025-05-10 | GSE296348 | GEO
Project description:We investigated age-related changes in the transcriptional profile of skeletal muscle in 5 month old (young) and 25 month old (old) C57BL/6NHsd mice using high density oligonucleotide arrays (22,690 transcripts probed). We identified 712 transcripts that are differentially expressed in young (5 month old) and old (25-month old) mouse skeletal muscle. Caloric restriction (CR) completely or partially reversed 87% of the changes in expression. Examination of individual genes revealed a transcriptional profile indicative of increased p53 activity in the older muscle. To determine whether the increase in p53 activity is associated with transcriptional activation of apoptotic targets, we performed RT-PCR on four well known mediators of p53-induced apoptosis: puma, noxa, tnfrsf10b and bok. Expression levels for these proapoptotic genes increased significantly with age (P<0.05), while CR significantly lowered expression levels for these genes as compared to control fed old mice (P<0.05). Age-related induction of p53-related genes was observed in multiple tissues, but was not observed in SOD2+/- and GPX4+/- mice, suggesting that oxidative stress does not mediate the observed age-related increase in expression. Western blot analysis confirmed that protein levels for both p21 and GADD45a, two established transcriptional targets of p53, were higher in the older muscle tissue. These observations support a role for p53-mediated apoptotic activity in mammalian aging. Keywords: aging, calorie restriction, muscle, p53
2006-12-01 | GSE6323 | GEO
Project description:We report the scRNA-seq of mononuclear cells isolated from skeletal muscle of young and old mice.
2022-05-20 | GSE172410 | GEO
Project description:We report RNA-seq of skeletal muscle (quadriceps) of young (6-month), old (24-month), and senolytic (Dasatinib + quercetin) treated mice
2022-05-20 | GSE184348 | GEO
Project description:Evidence from clinical trials and observational studies suggests that both progressive resistance training (PRT) and metformin delay a variety of age-related morbidities. Previously, we completed a clinical trial testing the effects of 14 weeks of PRT + metformin (metPRT) compared to PRT with placebo (plaPRT) on muscle hypertrophy in older adults. We found that metformin blunted PRT-induced muscle hypertrophic response. To understand potential mechanisms underlying the inhibitory effect of metformin on PRT, we analyzed the muscle transcriptome in 23 metPRT and 24 plaPRT participants. PRT significantly increased expression of genes involved in extracellular matrix remodeling pathways, and downregulated RNA processing pathways in both groups, however, metformin blunted the number of differentially expressed genes within these pathways compared to plaPRT. Pathway analysis showed that genes unique to metPRT modulated aging-relevant pathways, such as cellular senescence and autophagy. Differentially expressed genes from baseline biopsies in older adults compared to resting muscle from young volunteers were reduced following PRT in plaPRT and were further reduced in metPRT. We suggest that although metformin may blunt pathways induced by PRT to promote muscle hypertrophy, adjunctive metformin during PRT may have beneficial effects on aging-associated pathways in muscle from older adults.
2020-09-08 | GSE157585 | GEO
Project description:We report RNA-seq of single myofibers with different p21 expression level isolated from EDL muscle of young and old mice.
2022-05-20 | GSE172254 | GEO