Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Stat1 activation, through systemic interferon signaling, and upregulation of innate immune system receptors drives inflammaging, that is ameliorated by dietary restriction intervention

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE162803 | GEO | 2022/08/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Stat1 activation, through systemic interferon signaling, and upregulation of innate immune system receptors drives inflammaging, that is ameliorated by dietary restriction intervention [RNA-seq]

Project description:Aging is the result of an accumulation of molecular damages, driven by multiple factors like metabolic and oxidative stress, (epi)genetic alterations, and microbiome dysbiosis. In addition, aging is characterized by a chronic, low-grade inflammation known as inflammaging that represents a high significant risk factor for most, if not all, age-related diseases. Dietary restriction (DR) is the best-known non-invasive method to ameliorate the aging phenotype in many organisms. While it has been shown that DR reduces the inflammation in some tissues, the molecular mechanisms in old individuals are still largely unknown. Here we identify a multi-tissue gene network which regulates the inflammaging and that is ameliorated by DR. Using transcriptional profiling (RNA-seq), we found that aging upregulates the innate immune system receptor together with the activation of a systemic interferon (IFN) signaling through the Interferon Regulatory Factors (Irf), inflammatory cytokines and finally Stat1 transcription factor. Our results suggest that DR is able to ameliorate inflammaging by downregulating the expression and the activity of almost all the components of this gene network. In addition, chromatin accessibility genome-wide analysis showed that the binding site of Irf and Stat1 in the promoter of their target genes are more open in aging and become closer upon DR treatment indicating a transcriptional control of the inflammaging phenotype involving epigenetic modifications. Our results provide a comprehensive understanding of the molecular network regulating the inflammation in aging and DR and present novel anti-inflammaging therapeutic targets.

2022-08-25 | GSE162802 | GEO

Stat1 activation, through systemic interferon signaling, and upregulation of innate immune system receptors drives inflammaging, that is ameliorated by dietary restriction intervention [ATAC-seq]

2022-08-25 | GSE162728 | GEO

Stat1 activation, through systemic interferon signaling, and upregulation of innate immune system receptors drives inflammaging, that is ameliorated by dietary restriction intervention

Project description:Stat1 activation, through systemic interferon signaling, and upregulation of innate immune system receptors drives inflammaging, that is ameliorated by dietary restriction intervention

| PRJNA683057 | ENA

Stat1 activation, through systemic interferon signaling, and upregulation of innate immune system receptors drives inflammaging, that is ameliorated by dietary restriction intervention [RNA-seq]

| PRJNA683062 | ENA

Stat1 activation, through systemic interferon signaling, and upregulation of innate immune system receptors drives inflammaging, that is ameliorated by dietary restriction intervention [ATAC-seq]

| PRJNA682754 | ENA

Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity.

Project description:Chronic inflammation predisposes to aging-associated disease, but it is unknown whether immunity regulation might be important for extending healthy lifespan. Here we show that in C. elegans, dietary restriction (DR) extends lifespan by modulating a conserved innate immunity pathway that is regulated by p38 signaling and the transcription factor ATF-7. Longevity from DR depends upon p38-ATF-7 immunity being intact but downregulated to a basal level. p38-ATF-7 immunity accelerates aging when hyperactive, influences lifespan independently of pathogen exposure, and is activated by nutrients independently of mTORC1, a major DR mediator. Longevity from reduced insulin/IGF-1 signaling (rIIS) also involves p38-ATF-7 downregulation, with signals from DAF-16/FOXO reducing food intake. We conclude that p38-ATF-7 is an immunometabolic pathway that senses bacterial and nutrient signals, that immunity modulation is critical for DR, and that DAF-16/FOXO couples appetite to growth regulation. These conserved mechanisms may influence aging in more complex organisms.

| S-EPMC6506407 | biostudies-literature

Does Calorie Restriction Modulate Inflammaging via FoxO Transcription Factors?

Project description:Calorie restriction (CR) has been shown to extend lifespan and retard aging-related functional decline in animals. Previously, we found that the anti-neoplastic and lifespan-extending effects of CR in mice are regulated by forkhead box O transcription factors (FoxO1 and FoxO3), located downstream of growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling, in an isoform-specific manner. Inflammaging is a term coined to represent that persistent low-level of inflammation underlies the progression of aging and related diseases. Attenuation of inflammaging in the body may underlie the effects of CR. Recent studies have also identified cellular senescence and activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome as causative factors of inflammaging. In this paper, we reviewed the current knowledge of the molecular mechanisms linking the effects of CR with the formation of inflammasomes, particularly focusing on possible relations with FoxO3. Inflammation in the brain that affects adult neurogenesis and lifespan was also reviewed as evidence of inflammaging. A recent progress of microRNA research was described as regulatory circuits of initiation and propagation of inflammaging. Finally, we briefly introduced our preliminary results obtained from the mouse models, in which Foxo1 and Foxo3 genes were conditionally knocked out in the myeloid cell lineage.

| S-EPMC7399912 | biostudies-literature

Restriction of essential amino acids dictates the systemic response to dietary protein dilution

Project description:Dietary protein dilution (DPD) promotes metabolic remodelling and health but the precise nutritional components driving this response remain elusive. Here we demonstrate that dietary amino acids (AA) are sufficient and necessary to drive the response to DPD. In particular, the restriction of dietary essential AA (EAA) supply, but not non-EAA, drives the systemic metabolic response to total AA deprivation. Furthermore, systemic deprivation of Thr and Trp, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Thr is also potentially limiting in low-protein diet fed humans, and dietary Thr restriction (DTR) retarded the development of obesity-associated metabolic dysfunction in mice. Liver-derived fibroblast growth factor 21 was required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of Thr biosynthetic capacity reversed the systemic response to DTR. Taken together, our studies demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.

2020-06-15 | PXD018205 | Pride

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction.

Project description:Despite regulation, brain iron increases with aging and may enhance aging processes including neuroinflammation. Increases in magnetic resonance imaging transverse relaxation rates, R2 and R2*, in the brain have been observed during aging. We show R2 and R2* correlate well with iron content via direct correlation to semi-quantitative synchrotron-based X-ray fluorescence iron mapping, with age-associated R2 and R2* increases reflecting iron accumulation. Iron accumulation was concomitant with increased ferritin immunoreactivity in basal ganglia regions except in the substantia nigra (SN). The unexpected dissociation of iron accumulation from ferritin-upregulation in the SN suggests iron dyshomeostasis in the SN. Occurring alongside microgliosis and astrogliosis, iron dyshomeotasis may contribute to the particular vulnerability of the SN. Dietary restriction (DR) has long been touted to ameliorate brain aging and we show DR attenuated age-related in vivo R2 increases in the SN over ages 7 - 19 months, concomitant with normal iron-induction of ferritin expression and decreased microgliosis. Iron is known to induce microgliosis and conversely, microgliosis can induce iron accumulation, which of these may be the initial pathological aging event warrants further investigation. We suggest iron chelation therapies and anti-inflammatory treatments may be putative 'anti-brain aging' therapies and combining these strategies may be synergistic.

| S-EPMC5115902 | biostudies-literature

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.

Project description:Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.

| S-EPMC7283339 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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