Role of DNA methylation in the dietary restriction mediated cellular memory
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE98356 | GEO | 2017/05/30
SECONDARY ACCESSION(S): PRJNA384803
REPOSITORIES: GEO
Similar Datasets
Project description:Dietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during ageing and extends lifespan in diverse species including rodents and rhesus monkeys. However the mechanisms by which DR interacts with the ageing process to improve health at old age are poorly understood. DNA methylation could play an important role in mediating the effects of DR, because it is sensitive to the effects of nutrition and can affect gene expression memory over time. Here we have profiled genome-wide changes in DNA methylation, gene expression and lipidomics in response to DR and ageing in mouse liver. DR strongly retarded age-related changes in DNA methylation. With ageing, DNA methylation became confined to genic elements and was associated with reduced gene expression, particularly of genes involved in lipid metabolism.
2017-02-24 | GSE92486 | GEO
Project description:Dietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at ¬old age remains elusive. Here, we conducted a late-life DR switch experiment employing 800 mice, by switching old animals from ad libitum (AL) to DR and vice versa. Strikingly, the switch from DR-to-AL acutely increased mortality, while the switch from AL-to-DR caused only a weak and gradual increase in survival, highlighting a memory of earlier nutrition. A significant association between fat preservation and survival response pointed to the adipose tissue as a potential memory source. Consistently, post-switch RNA-seq profiling in liver, brown (BAT) and white adipose tissue (WAT) demonstrated that the transcriptional and metabolic program of chronic DR remained largely refractory to the AL-to-DR switch in the two fat tissues, particularly in WAT. This loss of transcriptional flexibility coincides with a major proinflammatory signature in aged preadipocytes, which is prevented by chronic DR feeding. Integration of lipidomics confirmed impaired membrane lipogenesis and limited mitochondrial copy number increase under late-life DR as functional consequences of this memory effect. Together, our results provide evidence for a nutritional memory as a limiting factor for DR-induced longevity and metabolic remodeling of WAT in mammals.
2019-08-28 | GSE124772 | GEO
Project description:Even though these results have shown several key proteins played an import role in radiation tolerance mechanism of DR, they were lack of the deep protein coverage, global protein analysis as well as the dynamic changes of DR, which limits further understanding of biological changes in response to ionizing radiation. To the best of our knowledge, the global and specific radiation tolerance mechanism of DR has not been elucidated yet. Therefore, a label-free quantitative proteomics was applied to conduct a systematic and comprehensive proteomic analysis on DR after 6 kGy γ-irradiation at different time point. Differentially abundant proteins (DAPs) with a fold-change cutoff were reported. These proteins, providing a deep understanding of the molecular response to ionizing radiation.
2022-08-29 | PXD027969 | Pride
Project description:Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.
2013-11-08 | GSE40977 | GEO
Project description:We first demonstrate that non-genetically determined inter-individual differentially methylated regions (iiDMRs) can be temporally stable for at least two years. Then, we show that iiDMRS are associated with concomitant changes in chromatin state as measured by inter-individual differences in the levels of the histone variant H2A.Z. However, the correlation of promoter iiDMRs with gene expression is negligible and this correlation is not improved even by integrating H2A.Z information. We find that most promoter epialleles, whether genetically or non-genetically determined, are associated with low levels of transcriptional activity, depleted for house keeping genes, and either depleted for H3K4me3/enriched for H3K27me3, or lacking both these marks in human embryonic stem cells. These findings validate in an independent cohort. Interestingly, the key features of iiDMRs are reminiscent of those previously observed for promoters that undergo hyper-methylation in various cancers, in vitro cell culture, and human chronological ageing. H2A.z ChIP-seq, RNA-seq, and DNA methylation data (submitted separately) were collected for five normal individuals. T21/T22 and T31/T32 are monozygotic twins.
2013-04-22 | E-GEOD-46217 | biostudies-arrayexpress
Project description:Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we demonstrate that DR-induced optimization of immunological memory requires co-operation between memory T cells, the intestinal microbiota, and myeloid cells. Our data indicate that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes expansion of the commensal Bifidobacteria within the large intestine, which supplies the short-chain fatty acid acetate to myeloid cells. Acetate conditioning of the myeloid compartment during DR enhances their capacity to kill pathogens. Enhanced host protection during DR is abolished when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function critically dictates immune responsiveness to this dietary intervention. Altogether, DR induces both memory T cells and the gut microbiota to produce essential, distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings reveal how nutritional cues promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.
2024-02-21 | GSE223739 | GEO
Project description:Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we demonstrate that DR-induced optimization of immunological memory requires co-operation between memory T cells, the intestinal microbiota, and myeloid cells. Our data indicate that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes expansion of the commensal Bifidobacteria within the large intestine, which supplies the short-chain fatty acid acetate to myeloid cells. Acetate conditioning of the myeloid compartment during DR enhances their capacity to kill pathogens. Enhanced host protection during DR is abolished when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function critically dictates immune responsiveness to this dietary intervention. Altogether, DR induces both memory T cells and the gut microbiota to produce essential, distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings reveal how nutritional cues promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.
2023-12-13 | GSE242696 | GEO
Project description:Several studies have discussed the possibility that donor cell type may influence the epigenetics and differentiation potential of iPSCs, but it remains unclear whether iPS cells derived from different tissue sources reserve their epigenetic memory. Here, we clarify that iPSCs obtained from different tissues exhibit specific epigenetic patterns. We determined the DNA methylation profiles of 12 human cell lines, including 3 adult fibroblast cell-derived iPSC lines, 2 peripheral blood-derived mononuclear cell(PBMC)-derived iPSC lines, 2 amniotic cell-derived iPSC lines and the 5 corresponding parent cell lines. We found that the catalog of tissue-specific DNA methylation was preserved in the iPSC line as epigenetic memory during reprogramming.
2016-05-02 | GSE80969 | GEO
Project description:High dimensional single-cell analyses have improved the ability to resolve complex mixtures of cells from human disease samples; however, identifying disease-associated cell types or cell states in patient samples remains challenging due to technical and inter-individual variation. Here we present Mixed-Effects modeling of Associations of Single Cells (MASC), a reverse single cell association strategy for testing whether case-control status influences the membership of single cells in any of multiple cellular subsets while accounting for technical confounders and biological variation. Applying MASC to mass cytometry analyses of CD4+ T cells from the blood of rheumatoid arthritis (RA) patients and controls revealed a significantly expanded population of CD4+ T cells, identified as CD27- HLA-DR+ effector memory cells, in RA patients. The frequency of CD27- HLA-DR+ cells was similarly elevated in blood samples from a second RA patient cohort, and CD27- HLA-DR+ cell frequency decreased in RA patients who responded to immunosuppressive therapy. Mass cytometry and flow cytometry analyses indicated that CD27- HLA-DR+ cells were associated with RA. Compared to peripheral blood, synovial fluid and synovial tissue samples from RA patients contained ~5-fold higher frequencies of CD27- HLA-DR+ cells, which comprised ~10% of synovial CD4+ T cells. CD27- HLA-DR+ cells expressed a distinctive effector memory transcriptomic program with Th1- and cytotoxicity-associated features, and produced abundant IFNg and granzyme A protein upon stimulation. Thus MASC identified the expansion of a unique effector memory CD4+ T cell population in RA. We propose that MASC is a broadly applicable method to identify disease-associated cell populations in high-dimensional single cell data.
2018-09-13 | GSE118209 | GEO
Project description:In this study, we have analyzed DNA methylation changes upon aging of human dermal fibroblasts by using the HumanMethylation27 BeadChip assessing 27,578 unique CpG sites. Cells were isolated from skin samples donated by young (6-23 years) and elderly (60-73 years) patients undergoing surgical interventions. Strikingly, global DNA-methylation profiles of fibroblasts from the same anatomical site clustered closely together indicating that fibroblasts maintain positional memory even after in vitro culture.
2012-02-14 | GSE22595 | GEO