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Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse neocortex to investigate age-related gene expression changes

ABSTRACT: Aging is associated with major nuclear changes affecting genomic integrity and gene expression. Here we compare the gene expression profiles in the neocortex of young (5 months old) and old (30 months old) B6xC3 F1 mice. In a related study, we compare genes that change expression with age to SIRT1 associated genes identified by ChIP on chip (NimbleGen) and find a significant overlap, indicating that SIRT1 target genes are preferentially deregulated with age. Experiment Overall Design: Total neocortex RNA was hybridized on Affymetrix M430 2.0 arrays. RNA was isolated from five young (5 months) and 5 old (30 months) B6xC3 F1 mice, samples were hybridized individually.

ORGANISM(S): Mus musculus

SUBMITTER: Philipp Oberdoerffer

PROVIDER: E-GEOD-13120 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.

Oberdoerffer Philipp P Michan Shaday S McVay Michael M Mostoslavsky Raul R Vann James J Park Sang-Kyu SK Hartlerode Andrea A Stegmuller Judith J Hafner Angela A Loerch Patrick P Wright Sarah M SM Mills Kevin D KD Bonni Azad A Yankner Bruce A BA Scully Ralph R Prolla Tomas A TA Alt Frederick W FW Sinclair David A DA

Cell 20081101 5

Genomic instability and alterations in gene expression are hallmarks of eukaryotic aging. The yeast histone deacetylase Sir2 silences transcription and stabilizes repetitive DNA, but during aging or in response to a DNA break, the Sir complex relocalizes to sites of genomic instability, resulting in the desilencing of genes that cause sterility, a characteristic of yeast aging. Using embryonic stem cells, we show that mammalian Sir2, SIRT1, represses repetitive DNA and a functionally diverse set ...[more]

PMID: 19041753

Similar Datasets

Project description:Aging is associated with major nuclear changes affecting genomic integrity and gene expression. Here we compare the gene expression profiles in the neocortex of young (5 months old) and old (30 months old) B6xC3 F1 mice. In a related study, we compare genes that change expression with age to SIRT1 associated genes identified by ChIP on chip (NimbleGen) and find a significant overlap, indicating that SIRT1 target genes are preferentially deregulated with age. Keywords: gene expression comparison, age-comparison

2008-11-26 | GSE13120 | GEO

SIRT1 redistribution on chromatin promotes genome stability but alters gene expression during aging

Project description:This SuperSeries is composed of the following subset Series: GSE13075: SIRT1 and H1AcK26 promoter-association in mouse ES cells changes upon oxidative stress GSE13120: Age-related gene expression changes in mouse neocortex Refer to individual Series

2010-05-15 | E-GEOD-13121 | biostudies-arrayexpress

Transcription profiling of mouse heart, brain, and skeletal muscle to determine the rffect of age, calorie restriction and resveratrol on gene expression

Project description:Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR. Experiment Overall Design: Heart, neocortex tissue, and gastrocnemius muscle was collected from young and old mice at 5 and 30 months of age, respectively; mice were subjected to either a calorie restricted diet or a control diet supplemented with resveratrol

2008-06-18 | E-GEOD-11291 | biostudies-arrayexpress

Gene expression profile in Liver, skeletal muscle, brown and white adipose tissues in mice after different interventions

Project description:SIRT1 is a NAD+-dependent protein deacetylase. SIRT1 plays key roles in metabolic regulation and adaptation. In this study, we wanted to compare gene expression profile in SIRT1 overexpressing mice to WT mice submitted to different intervention (caloric restriction and exercise training) in different tissues (liver, skeletal muscle, brown and white adipose tissues). SIRT1 transgenic model has already been described (Pfluger et al., 2008). Here we used homozygote transgenic mice which had been backcrossed to C57Bl/6N background. 3 months old WT and SIRT1tg mice were fed with a low fat diet. After sacrifice, total mRNA obtained from brown adipose were used for microarray. Caloric restriction (CR) : everyother day feeding during 3 months Exercise training (EX) : mice were housed in running wheel cages during 10 weeks

2015-07-14 | E-GEOD-70857 | biostudies-arrayexpress

Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging (microarray expression)

Project description:Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, the latter of which leads to its overexpression; in turn, Per2 suppresses Sirt1 transcription through binding to the Sirt1 promoter at the Clock/Bmal1 site. This negative reciprocal relationship between SIRT1 and PER2 was also observed in human hepatocytes. We further demonstrated that the absence of Sirt1 or the ectopic overexpression of Per2 in the liver resulted in a dysregulated pace of the circadian rhythm. The similar circadian rhythm was also observed in aged wild type mice. The interplay between Sirt1 and Per2 modulates aging gene expression and circadian-clock maintenance. To investigate hepatic SIRT1-dependent aging related genes, livers from wild type mice at 3 months (young), 12 months (middle age), and 19 months (old) of age, as well as Sirt1-deficient mice at 3 months of age were snap frozen and subject to RNA isolation and microarray analysis.

2016-08-08 | E-GEOD-54436 | biostudies-arrayexpress

SIRT1 but not its increased expression is essential for lifespan extension in caloric restricted mice.

Project description:The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging 2-5 month old male mice of 3 different genotypes (SIRT1+/+, SIRT1+/-, and SIRT1-/-) that had normal, reduced or no expression of SIRT1 were treated with either a 40% caloric restricted diet (CR) or an ad libitum diet (AL). 2-4 replicates of each experimental condition were used in the analysis.

2014-04-25 | E-GEOD-46895 | biostudies-arrayexpress

Transcription profiling of mouse brain to identify age-related transcriptional changes and the effect of dietary supplementation of vitamin E

Project description:We established the transcriptional profile of brain aging and examine the global effects of vitamin E supplementation on age-related alterations in expression in the aged mouse brain. Experiment Overall Design: Gene expression profiles were obtained from the neocortex tissues of 5-month-old controls, 30-month-old controls and 30-month old B6C3F1 mice with middle age-onset supplementation of alpha-tocopherol or a mixture of alpha and gamma-tocopherol (500mg/kg of each tocopherol).

2009-09-23 | E-GEOD-8150 | biostudies-arrayexpress

Expression data from young and old zebrafish brain.

Project description:Brains are sexually dimorphic in adult zebrafish. We dissected brains from young and old, adult zebrafish, from both males and females. Brains are not pooled but analyzed as indivual samples. Four groups of wild-type zebrafish (AB strain) were used for this study: young (7.5-8.5 months old) male and female and old (31-36 months old) male and female. There were three animals per group for a total of 12 animals in the study.

2014-02-19 | E-GEOD-53430 | biostudies-arrayexpress

Intestinal SIRT1 in the regulation of intestinal tissue homeostasis

Project description:The goal of this project is to investigate the role of SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase, in the regulation of intestinal tissue integrity. Using a mouse model with specific deletion of SIRT1 in intestinal epithelium (SIRT1 iKO mice), we recently discovered that deletion of intestinal SIRT1 in mice age-dependently elicits NF-κB signaling and other stress response pathways, activates intestinal secretory cells, enhances spontaneous inflammation, and alters commensal gut microbial composition. To understand the molecular mechanisms underlying these age-dependent phenotypes, we examined the transcriptomes of young (6-8 week old) and aged (24-month old) ilea and aged colons from Flox controls and SIRT1 iKO mice by microarray analysis.

2017-05-30 | GSE86475 | GEO

An aging-like phenotype occurs in Tif1γ-/- hematopoietic stem cells

Project description:To determine whether an accelerated aging-like phenotype occurs in hematopoiesis of young Tif1γ-/- mice (4 months old), we purified 200,000 hematopoietic stem cells (LSK: Lineage negative, Sca1+, c-Kit+) from Tif1γ-/- mice and performed high-throughput mRNA sequencing (RNA-seq). We compared this transcriptome to physiological aging by creating two other RNAseq libraries from young (4 months old) and old (20 months old) wild type mice.

2014-06-16 | GSE57396 | GEO

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