Comprehensive transcriptional profiling of porcine liver aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE123590 | GEO | 2019/03/06
REPOSITORIES: GEO
Similar Datasets
Project description:Aging and unhealthy diets are risks for metabolic diseases including liver cancer. Bile acid receptor farnesoid X receptor (FXR) knockout (KO) mice develop metabolic liver diseases and progress into liver cancer as they age, and Western diet (WD) intake facilitates liver carcinogenesis in those mice. This study aimed to uncover molecular signatures within the gut-liver axis for diet and age-linked liver diseases in FXR-dependent or independent manners. Many more transcripts were changed due to WD intake and aging in WT mice than those in FXR KO mice. In other words, WD intake and aging impact the hepatic transcriptomes and metabolomes in an FXR-dependent manner. In WT mice, WD/aging upregulated inflammation-related genes and downregulated genes involved in oxidative phosphorylation (OXPHOS). Urine metabolomes provided clear distinguishing for differential dietary intake. By contrast, the metabolomes of the liver, serum, or urine could reflect age differences. Further, irrespective of differential diets intake or ages, transcriptomes, metabolomes, and cecal microbiota distinguished WT and FXR KO. Western dietary patterns and aging share molecular commonality with FXR deactivation. Notably, WD, aging, and FXR deactivation commonly altered hepatic cell division-related transcripts (Cenpe, Ect2, Top2a, Kif20a, Tpx2, Nuf2, Kif18b, Aspm, E2f8, and Hmmr), which are associated with overall survival rate in HCC patients. In conclusion, FXR is essential for maintaining metabolic homeostasis in response to WD intake and aging. FXR activation helps to alleviate diet and/or aging-induced metabolic health issues.
2023-02-22 | GSE216375 | GEO
Project description:Adipose tissue mass and adiposity change throughout the lifespan. During aging, while visceral adipose tissue (VAT) tends to increase, peripheral subcutaneous adipose tissue (SAT) decreases significantly. Unlike VAT, which is linked to metabolic diseases, SAT has beneficial effects. However, the molecular details behind aging-associated loss of SAT remain unclear. Here we compare scRNA-seq of total SVF of SAT from young and aging mice to identify a novel Aging-dependent Regulatory Cell (ARC) that emerges in SAT of aged mice. Inguinal white adipose tissue (iWAT) was used as a representative SAT; iWAT pads of 2 mice from each age group were subjected to collagenase digestion and treated with a hypotonic buffer to remove red blood cells before subjection to scRNA-seq by 10X Genomics Chromium Single Cell Kit. The findings showed that ARCs express adipogenic markers but lack adipogenic capacity and inhibit differentiation of neighboring adipose precursors.
2021-03-25 | E-MTAB-10221 | biostudies-arrayexpress
Project description:Background: The obesity epidemic and the aging population of many western countries together with their associated diseases are major challenges for the healthcare. As obesity is a risk factor for many age related diseases, such as cancer, it is of importance to understand their interaction and the underlying molecular mechanisms. Lately, epigenetic programming in the form of DNA methylation and have been recognized for its importance in aging, obesity and several diseases. Method: Herein, the methylation level was determined for around 27000 CpG-islands in 46 DNA samples from adult peripheral blood with microarrays. The dependence for each CpG island with age, obesity and their interaction was ascertained with a general linear model. Results: The methylation level of more than 100 genomic sites were significantly altered with increasing age together with 10 additional sites that were differentially methylated with age in obese and lean individuals. The majority of the genomic sites were hypermethylated during aging, including the telomerase catalytic subunit (TERT). However, age dependent hypermethylation was prohibited or reverted in 8 of 10 regions in obese where an interaction between age and obesity was observed. Moreover, one region (LINC00304) was differentially methylated in obese and lean. Conclusion: This study provides evidence for an obesity influence on age driven epigenetic changes, which provide a molecular link between aging and obesity. This link and the identified markers may prove to be valuable biomarkers for the understanding of the molecular basis of aging, obesity and associated diseases. Bisulphite converted DNA from the 24 obese and 22 lean women were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2014-07-09 | E-GEOD-44763 | biostudies-arrayexpress
Project description:Older age is the primary risk factor for most chronic diseases, including Alzheimer’s disease (AD). Current preclinical models to study brain aging and AD are mainly transgenic and harbor mutations intended to mirror brain pathologies associated with human brain aging/AD (e.g., by increasing production of amyloid precursor protein, amyloid beta [Aβ], and/or phosphorylated tau, all of which are key pathological mediators of AD). Although these models may provide insight on pathophysiological processes in AD, none completely recapitulate the disease and its strong age-dependence, and there has been limited success in translating preclinical results and treatments to humans. Here, we describe two non-transgenic guinea pig (GP) models, a standard PigmEnTed (PET) strain and lesser-studied Dunkin-Hartley (DH) strain, that may naturally mimic key features of brain aging and AD in humans. We show that brain aging in PET GP is transcriptomically similar to human brain aging, whereas older DH brains are transcriptomically more similar to human AD. Both strains/models also exhibit increased neurofilament light chain (NFL, a marker of neuronal damage) with aging, and DH animals display greater S100 calcium-binding protein B (S100β), ionized calcium-binding adapter molecule 1 (Iba1), and Aβ and phosphorylated tau— which are all important markers of neuroinflammation-associated AD. Collectively, our results suggest that both the PET and DH GP may be useful, non-transgenic models to study brain aging and AD, respectively.
2022-03-19 | GSE198736 | GEO
Project description:Background: Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach. Results: We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age. Conclusions: This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research. We collected the longissimus dorsi muscles tissue from Jinhua pigs which aged 0.5 year and seven years and study the genome-wide DNA methylation difference between the two age periods.
2014-08-02 | E-GEOD-50716 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE24992: Drosophila brain microRNA expression with age: miRNA profiling GSE25007: Drosophila brain gene expression with age: mRNA profiling GSE25008: Drosophila brain gene expression between wildtype and miR-34 null flies Refer to individual Series. Aging is the most prominent risk factor for human neurodegenerative disease, but underlying mechanisms that connect two processes are less well characterized. With age, the brain undergoes functional decline and perhaps degeneration. Such decline may not just contribute to normal aging, but also enhance susceptibility to and progression of age-related neurodegenerative diseases. Therefore, defining intrinsic factors and pathways that underline the normal integrity of the adult nervous system may lead to insights that potentially link aging and neurodegeneration. Here, we report a highly conserved microRNA (miRNA), miR-34, as a modulator of aging and neurodegeneration. Using Drosophila, we show that fly miR-34 expression is brain-enriched and strikingly upregulated with age. Functional studies reveal that, whereas animals without miR-34 are normal as young adults, upon aging, they gradually show late-onset deficits characteristic of accelerated brain aging; these include a transcriptional signature of aged animals, coupled with rapid functional decline, loss of brain integrity, followed by a catastrophic decline in adult viability. Moreover, upregulation of miR-34 protects against neurodegeneration induced by pathogenic human polyglutamine (polyQ) disease protein. We next reveal a dramatic effect of miR-34 to silence the Eip74EF gene of steroid hormone pathways in the adult, which is crucial to maintain the normal aging. Collectively, these data define a miR-34-mediated mechanism that specifically affects long-term integrity of the adult nervous system. miR-34 function in Drosophila may thus present a link that functionally connects aging and neurodegeneration. Our studies implicate essential roles of miRNA- dependent pathways in maintenance of the adult brain, disease pathogenesis and healthy aging.
2011-12-23 | E-GEOD-25009 | biostudies-arrayexpress
Project description:In this study, we performed a dose escalation study of whole-liver irradiation in miniature pigs and established a novel pig model for the severe form of RILD largely resembling the clinical and histological features of the human diseases, especially VOD and hepatic necrosis. Furthermore, taking advantage of serial liver biopsy in large-sized animal, we dissected the dynamics of cellular events essential for irreversible liver dysfunction in RILD. Unexpectedly, ferroptosis was also detected in irradiated pig liver samples.
2023-04-04 | GSE200123 | GEO
Project description:There is a growing realization that some aging-associated phenotypes/diseases have an epigenetic basis. Here we report the first genome-scale study of epigenomic dynamics during normal human aging. We identify aging-associated differentially methylated regions (aDMRs) in whole blood in a discovery cohort, and then replicate these aDMRs in sorted CD4+ T-cells and CD14+ monocytes in an independent cohort, suggesting that aDMRs occur in precursor haematopoietic cells. Further replication of the aDMRs in buccal cells, representing a tissue that originates from a different germ-layer compared with blood, demonstrates that the aDMR signature is a multi-tissue phenomenon. Moreover, we demonstrate that aging-associated DNA hypermethylation occurs predominantly at bivalent chromatin domain promoters. This same category of promoters, associated with key developmental genes, is frequently hypermethylated in cancers and in vitro cell culture, pointing to a novel mechanistic link between aberrant hypermethylation in cancer, aging, and cell culture. We measured the methylation state of 27,578 CpG sites (Illumina HumanMethylation27 array) in whole blood samples from 93 heathy human females aged between 49 and 74, to discover sites which change methylation state with age.
2010-06-24 | E-GEOD-20236 | biostudies-arrayexpress
Project description:<p>The incidence of intestinal diseases increases with age, but the regulators of gut aging and the molecules linking gut aging and diseases remain largely unknown. By profiling the transcriptome, proteome, phosphoproteome and metabolome of 104 <em>Macaca fascicularis</em> large intestinal tissues, we unveiled asynchronous aging within the proximal and distal colon. The levels of many gene products, phosphosites and metabolites changed with age in a location- and sex-dependent manner, and many of these changes occurred at distinct rates or even in opposite directions at different locations. Assessment of 60 age-related molecules (genes, phosphosites, metabolites) across<em> C. elegans</em>, mice, and cell lines identified 32 crucial regulators of gut atrophy and barrier integrity. Notably, we found that tryptophan metabolism via the kynurenine and serotonin (5-HT) pathways was more active in the proximal and distal colon, respectively. In a mouse colitis model, reducing 5-HT production with a Tph1 inhibitor alleviated distal but not proximal colitis, while adding 5-HT aggravated distal symptoms, indicating that distal colitis is more sensitive to 5-HT fluctuations. Moreover, we identified 24 proteins, particularly HPX, that potentially link gut aging to colorectal cancer (CRC). High levels of HPX in CRC predicted poor prognosis in patients older than 50 yr but not in younger patients, suggesting that an age-linked HPX increase in the gut may contribute to CRC progression. Collectively, this work reveals the heterogeneity of large intestinal aging in non-human primates and offers promising targets for preventing gut aging and diseases.</p>
2023-12-14 | MTBLS7612 | MetaboLights
Project description:A transcriptome-wide analysis of human liver for demonstrating differences between young and old humans has not yet been performed. However, pinpointing major age-related alterations in hepatic gene expression may identify ontogenetic shifts with important hepatic and systemic con-sequences, provide novel pharmacogenetic information, offer clues to efficiently counteract symptoms of old age, and improve the overarching understanding of ontogeny and individual decline. By applying next-generation sequencing and subsequent statistical and bioinformatic [Ensemble Feature Selection (EFS)] analysis, we identified 44 transcripts among 60,617 total and 19,986 protein-encoding transcripts that significantly (p = 0.0003 to 0.0464; EFS score >0.3: 16 transcripts; EFS score >0.2: 28 transcripts) differ between young and old livers. Genes encoding for 25 of these highly age-related transcripts were assigned to the categories ‘regulome’, ‘in-flammaging’, ‘regeneration’, and ‘pharmacogenes’, plus two genes that did not match these cate-gories. Our results have major implications in the area of ontogeny/aging and for the age-dependently increased occurrence of non-alcoholic fatty liver, steatohepatitis, and hepatocellular carcinoma. In addition, we present a broadly substantiated and testable hypothesis on a genetical-ly governed ‘aging cascade’, wherein the protein phosphatase 1 regulatory subunit 10 (PPP1R10) gene acts as a putative ontogenetic master regulator, which is prominently flanked by the genes for the insulin-like growth factor-binding protein acid labile subunit (IGFALS) and dual specificity phosphatase 1 (DUSP1). The results of this transcriptome-wide analysis of human liver offer potential clues towards developing better therapeutic interventions against major liver diseases and increased insight into key mechanisms underlying aging.
2021-11-30 | GSE183915 | GEO