Reduced Expression of the Proto-oncogene Myc Increases Mouse Longevity and Enhances Healthspan
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jeffrey Hofmann
PROVIDER: E-GEOD-55272 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Using full-genome arrays, the expression of all XMEs was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver and compared to young adults. Fetal and neonatal life stages had a dramatic effect on XME expression compared to the relatively minor effects of old age. At all life stages except PND30 down-regulated genes outnumbered up-regulated genes. The altered XMEs included those in all of the major metabolic phases including phase I (alcohol and aldehyde dehydrogenase and Cyp genes), phase II (aldo-keto reductase, glutathione-S-transferases, sulfotransferases and UDP-glucuronosyl transferases) and phase III (transporters). We have generated a comprehensive catalog of XME hepatic gene changes through the life stages of the mouse that can be used to predict chemicals and chemical classes different life stages are more sensitive to. Some CEL files used in this study have been submitted through GSE21224. Keywords: gene expression/microarray We characterized gene expression changes in the developing mouse liver at gestational days (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver using full-genome microarrays and compared these changes to that in the adult liver.. We also compared results to GD19, PND32, and PND67 C3H mice. Total RNA was isolated from liver samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 28 samples, four mice in each of the age groups for C57BL/6 and C3H, were analyzed.
2010-10-01 | E-GEOD-21716 | biostudies-arrayexpress
Project description:Episodes of chronic stress can result in psychic disorders like post-traumatic stress disorder, but also promote the development of metabolic syndrome and type 2 diabetes. We hypothesize that muscle, as main regulator of whole-body energy expenditure, is a central target of acute and adaptive molecular effects of stress in this context. Here, we investigate the immediate effect of a stress period on energy metabolism in Musculus gastrocnemius in our established C57BL/6 chronic variable stress (Cvs) mouse model. Cvs decreased lean body mass despite increased energy intake, reduced circadian energy expenditure (EE), and substrate utilization. Cvs altered the proteome of metabolic components but not of the oxidative phosphorylation system (OXPHOS), or other mitochondrial structural components. Functionally, Cvs impaired the electron transport chain (ETC) capacity of complex I and complex II, and reduces respiratory capacity of the ETC from complex I to ATP synthase. Complex I-OXPHOS correlated to diurnal EE and complex II-maximal uncoupled respiration correlated to diurnal and reduced nocturnal EE. Bioenergetics assessment revealed higher optimal thermodynamic efficiencies (ƞ-opt) of mitochondria via complex II after Cvs. Interestingly, transcriptome and methylome were unaffected by Cvs, thus excluding major contributions to supposed metabolic adaptation processes. In summary, the preclinical Cvs model shows that metabolic pressure by Cvs is initially compensated by adaptation of mitochondria function associated with high thermodynamic efficiency and decreased EE to manage the energy balance. This counter-regulation of mitochondrial complex II may be the driving force to longitudinal metabolic changes of muscle physiological adaptation as the basis of stress memory.Chronic stress targets mitochondrial respiratory efficiency in the skeletal muscle of C57BL/6 mice.Nikolic A, Fahlbusch P, Wahlers N, Riffelmann NK, Jacob S, Hartwig S, Kettel U, Dille M, Al-Hasani H, Kotzka J, Knebel B. Cell Mol Life Sci. 2023 Mar 29;80(4):108. doi: 10.1007/s00018-023-04761-4.PMID: 36988756
2024-03-08 | PXD042472 | Pride
Project description:Episodes of chronic stress can result in psychic disorders like post-traumatic stress disorder, but also promote the development of metabolic syndrome and type 2 diabetes. We hypothesize that muscle, as main regulator of whole-body energy expenditure, is a central target of acute and adaptive molecular efects of stress in this context. Here, we investigate the immediate efect of a stress period on energy metabolism in Musculus gastrocnemius in our established C57BL/6 chronic variable stress (Cvs) mouse model. Cvs decreased lean body mass despite increased energy intake, reduced circadian energy expenditure (EE), and substrate utilization. Cvs altered the proteome of metabolic components but not of the oxidative phosphorylation system (OXPHOS), or other mitochondrial structural components. Functionally, Cvs impaired the electron transport chain (ETC) capacity of complex I and complex II, and reduces respiratory capacity of the ETC from complex I to ATP synthase. Complex I-OXPHOS correlated to diurnal EE and complex II-maximal uncoupled respiration correlated to diurnal and reduced nocturnal EE. Bioenergetics assessment revealed higher optimal thermodynamic efciencies (ƞ-opt) of mitochondria via complex II after Cvs. Interestingly, transcriptome and methylome were unafected by Cvs, thus excluding major contributions to supposed metabolic adaptation processes. In summary, the preclinical Cvs model shows that metabolic pressure by Cvs is initially compensated by adaptation of mitochondria function associated with high thermodynamic efciency and decreased EE to manage the energy balance. This counter-regulation of mitochondrial complex II may be the driving force to longitudinal metabolic changes of muscle physiological adaptation as the basis of stress memory.
2023-03-31 | PXD035798 | Pride
Project description:New mechanisms-of-action of anthocyanins (ACNs) provided by a red-fleshed apple compared with a white-fleshed apple ACN-poor, and with an ACN-rich extract on the proteome profile of aorta and heart as cardiovascular key tissues were determined. Hypercholesterolemic Wistar rats were separated into the corresponding groups to analyze the proteomic profile of the aorta and heart tissues using nano-liquid chromatography coupled to mass-spectrometry. Red-fleshed apple downregulated CRP, C1QB and CFP related-inflammation. White-fleshed apple reduced C1QB, CFB, CFD, C3, and C9 related to the complement system, reduced MB and CP related to iron metabolism, and increased ME1, PKM, and PC related to energy homeostasis. ACN-rich extract increased FMOD, TAGLN, and CAP1 related to cellular structure and decreased PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Red-fleshed apple rich in ACNs suggested an anti-inflammatory effect while white-fleshed apple reduced the complement system protein-related. An apple matrix effect reduced inflammatory proteins regardless their ACN content.
2022-04-04 | PXD018885 | Pride
Project description:Catechol-O-methyltransferase (COMT) is an ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity (Andersen & Skorpen, 2009) and risk for developing psychiatric disorders (Harrison & Tunbridge, 2008). A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure-dependent protein translation (Nackley et al., 2006). However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have pursued a genome-wide approach to examining gene expression in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed. This expression difference was validated with qPCR. A B2-B4 Short Interspersed Element (SINE) was inserted in the 3'UTR of Comt1 in 14 strains that also shared a common haplotype. Experiments using mammalian expression vectors of full-length cDNA clones with and without the SINE element demonstrate that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3'UTR B2-B4 SINE element, regulates Comt1 expression and mouse behavior. Brain region samples were isolated from male and female mice of 29 strains (n = 3), 129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ tf/J, BUB/BnJ , C3H/HeJ, C57BL/6J, C57BR/cdJ, C58/J, CBA/J, CE/J, DBA/2J, FVB/NJ, I/LnJ, KK/HIJ, MA/MyJ, MRL/MpJ, NOD/LtJ, NON/LtJ, NZO/HILTJ, NZW/LacJ, P/J, PL/J, RIIIS/J, SJL/J, SM/J, SWR/J, and WSB/EiJ. Eight to ten week old male and female mice of each strain were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). The mice were habituated for one week prior to tissue collection. Mice were sacrificed by cervical dislocation without anesthesia to avoid gene expression differences in response to anesthetic. All dissections were conducted between the hours of 9:00AM to 11:30AM. Prefrontal cortex and nucleus accumbens were dissected as follows. Immediately following euthanasia, mice were decapitated and the whole brain was removed from the skull. The brain was then transferred, ventral side up, to an ice-cold brain matrix with 0.5mm spacing (505C Braintree Scientific). A single razor blade was placed into the first space on the brain matrix and the rostral surface of the brain was placed in the matrix and touching this blade. Thin, double-edged razor blades were placed in the twelve most anterior spaces. Following removal from the matrix, the 0.5 mm brain slices were placed flat onto an ice-cold dissection stage and specific regions dissected using anatomical landmarks as described below. The prefrontal cortex was taken from the slice corresponding to approximately 2.5 mm to 2.0 mm anterior to Bregma. To do so, a V-shaped wedge was made just medial to the corpus callosum with the apex terminating at about the lateral ventricle (viewed from the caudal side of the slice). Nucleus accumbens was taken from the adjacent slice approximately 2.0mm to 1.5mm anterior to Bregma. To isolate nucleus accumbens, 1mm punches were taken just ventromedial to the anterior commissure. All of the array data in this Series are from male mice.
2010-02-23 | E-GEOD-20160 | biostudies-arrayexpress
Project description:Analysis of livers of male and female B6C3F1 mice exposed to prototype treatments from five classes of model hepatotoxicants. These hepatotoxicants include compounds that activate the peroxisome proliferator-activated receptor (PPAR), induce the inflammatory response, activate the constitutive androstane receptor (CAR), stimulate the hypoxia signal transduction pathway, and activate the aryl-hydrocarbon receptor (AHR). The results provide insights into the shared and unique pathways that are activated across these model hepatotoxicants. Exposures of mice of both sexes were initiated at 7 weeks of age. Matched vehicle controls were run concurrently with each exposure and gene expression levels in liver tissue compared between exposed and control animals.
2014-02-21 | E-GEOD-55084 | biostudies-arrayexpress
Project description:Kidney miRNA expression was examined in F344 rats at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age in both sexes using Agilent miRNA microarrays. 311 miRNAs were found to be expressed in at least one age and sex. Filtering criteria of ?1.5 fold change and ANOVA (FDR <5%) revealed 174 differentially expressed miRNAs in the kidney; 173 and 34 miRNAs exhibiting age and sex effects, respectively. Principal component analysis revealed age effects predominated over sex effects, with 2 week miRNA expression being much different from other ages. No significant sexually dimorphic miRNA expression was observed from 5 to 8 weeks, while the most differential expression (13 miRNAs) was observed at 21 weeks. Potential target genes of these differentially expressed miRNAs were identified. Pathway analysis was used to investigate the possible roles of these target genes in age- and sex-specific differences. Untreated male and female F344 rats from 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age (n=5) were sacrificed by CO2 asphyxiation, whole kidneys collected and homogenized, total RNA, including small RNA fraction, was used for miRNA expression arrays (Agilent).
2015-01-10 | E-GEOD-64842 | biostudies-arrayexpress
Project description:LRAT knockout mice on vitamin A sufficient or deficient diets were compared to age-matched wild type mice on a vitamin A sufficient diet RNA was isolated from right ventricle of the heart and one array was run for each sample.
2016-07-25 | E-GEOD-74905 | biostudies-arrayexpress
Project description:LRAT knockout mice on vitamin A sufficient or deficient diets were compared to age and gender matched wildtype mice on a vitamin A sufficient diet RNA was isolated from the left ventricle of the heart and one array was run for each sample.
2016-07-25 | E-GEOD-74904 | biostudies-arrayexpress
Project description:The experiment aims at a characterization of gene expression changes in duodenum during caloric restriction. The C57BL6 mice were restricted their food intake to 75% of their normal daily portion. The food was delivered daily around 4-6pm for 14 days. The mice were housed with free access to water. The control age-matched mice were fed ad libitum. The publication associated with this dataset concerns WT mice only. However, the experiment and microarray data normalization was performed for samples of WT and PPARgVillinCRE mice together. Thus for analysis reproducibility reasons data of all samples is made available.
2018-07-27 | E-MTAB-6248 | biostudies-arrayexpress