| Title |
Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets
|
|---|---|
| Published in |
Diabetologia, December 2015
|
| DOI | 10.1007/s00125-015-3837-8 |
| Pubmed ID | |
| Authors |
Ionel Sandovici, Constanze M. Hammerle, Wendy N. Cooper, Noel H. Smith, Jane L. Tarry-Adkins, Benjamin J. Dunmore, Julien Bauer, Simon R. Andrews, Giles S. H. Yeo, Susan E. Ozanne, Miguel Constância |
| Abstract |
Ageing is a major risk factor for development of metabolic diseases such as type 2 diabetes. Identification of the mechanisms underlying this association could help to elucidate the relationship between age-associated progressive loss of metabolic health and development of type 2 diabetes. We aimed to determine molecular signatures during ageing in the endocrine pancreas. Global gene transcription was measured in pancreatic islets isolated from young and old rats by Ilumina BeadChip arrays. Promoter DNA methylation was measured by Sequenom MassArray in 46 genes that showed differential expression with age, and correlations with expression were established. Alterations in morphological and cellular processes with age were determined by immunohistochemical methods. Age-related changes in gene expression were found at 623 loci (>1.5-fold, false discovery rate [FDR] <5%), with a significant (FDR < 0.05) enrichment in genes previously implicated in islet-cell function (Enpp1, Abcc8), type 2 diabetes (Tspan8, Kcnq1), inflammatory processes (Cxcl9, Il33) and extracellular matrix organisation (Col3a1, Dpt). Age-associated transcriptional differences negatively correlated with promoter DNA methylation at several loci related to inflammation, glucose homeostasis, cell proliferation and cell-matrix interactions (Il33, Cxcl9, Gpr119, Fbp2, Col3a1, Dpt, Spp1). Our findings suggest that a significant proportion of pancreatic islets develop a low-grade 'chronic' inflammatory status with ageing and this may trigger altered functional plasticity. Furthermore, we identified changes in expression of genes previously linked to type 2 diabetes and associated changes in DNA methylation that could explain their age-associated dysregulation. These findings provide new insights into key (epi)genetic signatures of the ageing process in islets. |
X Demographics
The data shown below were collected from the profiles of 15 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 20% |
| Canada | 2 | 13% |
| United Kingdom | 2 | 13% |
| Germany | 1 | 7% |
| Australia | 1 | 7% |
| Unknown | 6 | 40% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 10 | 67% |
| Scientists | 4 | 27% |
| Practitioners (doctors, other healthcare professionals) | 1 | 7% |
Mendeley readers
The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Sweden | 1 | 2% |
| Unknown | 53 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 22% |
| Student > Master | 10 | 18% |
| Student > Ph. D. Student | 6 | 11% |
| Professor | 5 | 9% |
| Student > Bachelor | 5 | 9% |
| Other | 10 | 18% |
| Unknown | 7 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 19 | 35% |
| Medicine and Dentistry | 13 | 24% |
| Agricultural and Biological Sciences | 3 | 5% |
| Computer Science | 2 | 4% |
| Neuroscience | 2 | 4% |
| Other | 5 | 9% |
| Unknown | 11 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 March 2016.
All research outputs
#3,711,174
of 22,840,638 outputs
Outputs from Diabetologia
#1,690
of 5,035 outputs
Outputs of similar age
#63,832
of 390,599 outputs
Outputs of similar age from Diabetologia
#21
of 70 outputs
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