Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Epigenetic and transcriptomic signature of aging in human liver [expression]

ABSTRACT: Gene expression profiling of liver biopsies collected from 33 healthy liver donors ranging from 13 to 90 years old. The Affymetrix HG-U133 Plus 2.0 GeneChip platform was used to evaluate gene-expression. Total RNA (including miRNAs) was extracted using the mirVana miRNA Isolation Kit (Ambion); cDNA synthesis, biotin-labelled target synthesis, hybridization, staining and scanning were performed according to Affymetrix standard protocol. This dataset is part of the TransQST collection.

ORGANISM(S): Homo sapiens

SUBMITTER: Maria Giulia Bacalini

PROVIDER: E-GEOD-107037 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

Bacalini Maria Giulia MG Franceschi Claudio C Gentilini Davide D Ravaioli Francesco F Zhou Xiaoyuan X Remondini Daniel D Pirazzini Chiara C Giuliani Cristina C Marasco Elena E Gensous Noémie N Di Blasio Anna Maria AM Ellis Ewa E Gramignoli Roberto R Castellani Gastone G Capri Miriam M Strom Stephen S Nardini Christine C Cescon Matteo M Grazi Gian Luca GL Garagnani Paolo P

The journals of gerontology. Series A, Biological sciences and medical sciences 20190101 1

The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8,823 age-associated differentially meth ...[more]

PMID: 29554203

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Project description:Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR can lead to increases in liver weight in part through hepatocyte replication similar to a large number of compounds that activate other nuclear receptors such as the peroxisome proliferator-activated receptor alpha and the constitutive activated receptor (CAR). PXR controls the expression of a large battery of genes involved in xenobiotic metabolism. Identification of genes that are accurate predictors of PXR activation would be useful in high-throughput screens to assess potential toxicity and drug-drug interactions. Here, we identified PXR-dependent genes in the mouse liver after exposure to pregnenolone 16alpha-carbinonitrile (PCN), a chemical that is often used as a model PXR agonist. The animal studies were carried out at the University of Kansas Medical Center (Kansas City, KS) under federal guidelines for the use and care of laboratory animals and was approved by the KUMC Institutional Animal Care and Use Committee. Eight-week-old adult C57BL/6 mice were purchased from Jackson Laboratories (Bar Harbor, ME). Generation of the PXR-null mice was previously described (Staudinger et al., (2001), Proc Natl Acad Sci USA 98:3369M-bM-^@M-^S3374). PXR-null breeder pairs were engineered and backcrossed into the C57BL/6 background. Adult male wild-type mice and PXR-null mice were maintained on standard laboratory chow and were allowed food and water ad libitum. All mice were treated once a day i.p. with either vehicle (corn oil) or PCN at 400 mg/kg/day for 4 days. Livers were removed 24-hrs after the last dose. Portions of the livers were rapidly snap-frozen in liquid nitrogen and stored at -70M-BM-0C until analysis. Liver gene expression analysis was performed according to the Affymetrix recommended protocol using Affymetrix Mouse Genome 430 2.0 GeneChipsM-BM-.. Total RNA (5 M-NM-<g per sample) was labelled using the AffymetrixM-BM-. One-Cycle cDNA Synthesis protocol and hybridized to arrays as described by the manufacturer (AffymetrixM-BM-., Santa Clara, CA). Microarray hybridizations were conducted overnight at 45M-BM-0C while rotating in an Affymetrix hybridization oven. After 16 hours of hybridization, the cocktail was removed and the arrays were washed and stained in an Affymetrix GeneChipM-BM-. fluidics station 450 according to the Affymetrix-recommended protocol. Arrays were scanned on an Affymetrix GeneChipM-BM-. scanner. Four mice per group were examined.

Project description:To determine the effects of age and lipoic acid supplementation on hepatic gene expression, we fed young (3 months) and old (24 months) male Fischer 344 rats a diet with or without 0.2% (w/w) R-?-lipoic acid (LA) for two weeks. Total RNA isolated from liver tissue was analyzed by Affymetrix microarray to examine changes in transcriptional profile. Results showed an increase in pro-inflammatory gene expression in the aging liver, with increased immune cell function and tissue remodeling genes, representing 45% of the age-related transcriptome changes. Increased inflammation was corroborated by increases in soluble ICAM1 levels with age. There were also observed age-related increases in transcription of genes related to lipid and cholesterol synthesis including Acetyl CoA Carboxylase (Acacb) and Fatty acid Synthase (Fasn). Supplementation of old animals with LA did not reverse this necro-inflammatory phenotype, yet limited age-associated hepatic dyslipidemia. Dietary LA further affected a small but concerted number of hepatic genes regardless of age. These included declines in lipid and bile synthesis genes. Decline in lipid synthesis genes was further corroborated by a decrease in Fasn and Acc protein levels. Intriguingly, LA also altered the expression of genes governing circadian rhythm, most notably Bmal1, Npas2, and Per2, which changed in a coordinated manner with respect to their rhythmic transcription. Thus, advanced age is associated with a necro-inflammatory phenotype and increased lipid synthesis, while chronic LA supplementation influences hepatic genes associated with energy metabolism and circadian rhythm regardless of age. Young (3 months) and old (24 months) Fischer 344 male rats were fed an AIN-93M diet ± 0.2% (w/w) R-?-lipoic acid for two weeks prior to sacrifice. Total RNA was extracted from the median lobe of the liver and analyzed using Affymetrix Rat Genome 230 2.0 Genechips. There were hybridizations for 8 animals in each of the young control, young LA-supplemented, and old control groups, and 6 animals in the old LA-supplemented group. There are only 6 animals in the old LA group because two animals died during the two-week feeding period. This is the reason for nonsequential numbering of animals in this group.

Dataset Information

Epigenetic and transcriptomic signature of aging in human liver [expression]

Publications

Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

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