Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In Vivo Transcriptomic Profiling using Cell Encapsulation Identifies Effector Pathways of Systemic Aging

ABSTRACT: Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE193665 | GEO | 2022/03/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

In-vivo Transcriptomic Profiling of Systemic Aging using Stem Cell Encapsulation

Project description:Sustained exposure to a young systemic environment rejuvenates aged tissues and promotes stem cell function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint direct effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human stem cells in highly diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging independent of physical cellular interactions in-vivo.

2022-03-05 | GSE111401 | GEO

Young blood-derived platelet factors abate inflammation and rescue recognition in aging.

Project description:We show that platelet factors transfer rejuvenating effects of young plasma to the aging brain. Proteomic analysis of plasma from young and aged mice identified age-related changes in platelets. Systemic exposure of aged animals to the platelet fraction of young plasma decreased hippocampal neuroinflammation at a transcriptional and cellular level and ameliorated cognitive impairments. We identified the platelet-derived chemokine CXCL4/Platelet Factor-4 (PF4) as a pro-youthful circulating factor. Systemic PF4 administration decreased age-related neuroinflammation, restored the aging peripheral immune system to a more youthful state, and improved hippocampal-dependent learning and memory in aged mice.

2023-06-20 | GSE173254 | GEO

Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle

Project description:In this study, we investigated signaling pathways in Skeletal muscle precursors that are altered with aging and age-related deficits in muscle regenerative potential. We performed fluorescence activated cell sorting (FACS) to obtain highly purified skeletal muscle satellite cells from young, middle-aged and old mice. Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction. We used Affymetrix Mouse Genome array to identify global transcriptional changes associated with age in skeletal muscle precursors.

2014-05-08 | E-GEOD-50821 | biostudies-arrayexpress

Regulation of aged skeletal muscle regeneration by extracellular

Project description:Heterochronic blood exchange (HBE) has demonstrated that circulating factors restore youthful features to aged tissues. However, the systemic mediators of those rejuvenating effects remain poorly defined. We show that the beneficial effect of young blood on aged muscle regeneration was diminished when serum was depleted of extracellular vesicles (EVs). Whereas EVs from young animals rejuvenate aged cell bioenergetics and skeletal muscle regeneration, aging shifts EV subpopulation heterogeneity and compromises downstream benefits on recipient cells. Machine learning classifiers revealed that aging shifts the nucleic acid, but not protein, fingerprint of circulating EVs. Alterations in sub-population heterogeneity were accompanied by declines in transcript levels of the pro-longevity protein, α-Klotho, and injection of EVs improved muscle regeneration in a Klotho mRNA-dependent manner. These studies demonstrate that EVs play a key role in the rejuvenating effects of HBE and that Klotho transcripts within EVs phenocopy the effects of young serum on aged skeletal muscle.

2021-07-01 | GSE176478 | GEO

Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle

2014-05-08 | GSE50821 | GEO

Platelet factor 4 (PF4) is induced by klotho and rejuvenates cognition and its molecular signature in the aging hippocampus

Project description:Platelet factors regulate wound healing and also signal from the blood to the brain. However, whether platelet factors modulate cognition, a highly valued and central manifestation of brain function, is unknown. Here, we show that systemic platelet factor 4 (PF4) modulates cognition and its molecular signature. Klotho, a longevity and cognition-enhancing protein, acutely activated platelets and increased circulating platelet factors, most robustly platelet factor 4 (PF4). To directly test PF4 effects on the brain, we treated mice with vehicle or systemic PF4. In young mice, PF4 enhanced synaptic plasticity and cognition. In aging mice, PF4 restored cognitive deficits and rejuvenated a molecular signature of cognition in the aging hippocampus. Augmenting platelet factors such as PF4, a possible messenger of klotho, may enhance cognition in the young brain and rejuvenate cognitive deficits in the aging brain.

2023-06-24 | GSE171929 | GEO

Transcriptome analysis of common and diverged circulating miRNAs between arterial and venous during aging

Project description:Background: miRNAs derived from peripheral venous blood gained extensive attention as clinical biomarkers, while arterial miRNAs exhibited slightly different expression profiles. We compared the expression profiles of venous- and arterial-derived plasma miRNA between young and aged male SD rats by next-generation sequencing, in order to explore whether peripheral venous miRNAs can represent entire circulating vessels in abnormal conditions like aging. Results: MSigDB Hallmark Gene Set reference and TAM 2.0 server were used to investigate the enriched functions and associated diseases. The aging-related de-regulated miRNAs in artery and vein shown similar enriched functional terms. Of note, refer to the arterial-versus-venous differential-expressed miRNA profiles, only a few miRNAs shared between young and aged rats. Among them, miR-450a/b and miR-223 shown the similar tendency between young and aged rat, while miR-136 and miR-503 etc displayed the opposite direction under the same scenario. Since miRNAs are under the control of their specific transcriptional factors, we further analyzed upstream regulators which influence miRNAs level for vascular vessel location. TransmiR v2.0 tool was used and found enriched upstream transcription factors like NFκB and SIRT1. These transcriptional factors could be organ-specific expression and/or regulated in physiological and aging states as parts of plausible causal factors. Conclusion: This study screened and analyzed the differential differential-expressed miRNA profiles in arterial and venous plasma under aging conditions, suggesting the importance of origin of candidate circulating miRNA biomarkers upon the certain scenario and its potential regulatory rule.

2019-10-03 | GSE138317 | GEO

Single-cell Transcriptomic Profiling of the Hypothalamic Median Eminence during Aging

Project description:Aging is a slow and progressive natural process that compromises the normal functions of cells, tissues, organs and systems. The aging of the hypothalamic median eminence (ME), a structural gate linking neural and endocrine systems, may impair hormone release, energy homeostasis and central sensing of circulating molecules, leading to systemic and reproductive aging. However, the molecular and cellular features of ME aging remain largely unknown. Here we describe the transcriptional landscape of young and middle-aged mouse ME at single-cell resolution, revealing the common and cell-type-specific transcriptional changes with age. The transcriptional changes in cell-intrinsic programs, cell-cell crosstalk and cell-extrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular, signaling and molecular levels. Importantly, our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome. Together, our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process, which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.

2022-02-03 | GSE179442 | GEO

A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Project description:Epigenetic alterations are a key hallmark of aging but have not been extensively explored in tissues. Here, using naturally aged murine liver as a model and extending study to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach and the first direct visualization of aged chromatin, we find that old cells show global H3K27me3-driven broad heterochromatinization and transcription suppression. At the local level, site-specific loss of H3K27me3 from promoters of genes encoding developmental transcription factors leads to expression in liver of non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.

2023-03-17 | GSE223480 | GEO

A hyper-quiescent chromatin state formed during aging is reversed by regeneration [ChIP-seq]

2023-03-17 | GSE185704 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data