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Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

Bacos, Karl LU ; Gillberg, Linn LU ; Volkov, Petr LU ; Olsson, Anders H LU ; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija LU and Almgren, Peter LU , et al. (2016) In Nature Communications 7.
Abstract

Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation... (More)

Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.

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Nature Communications
volume
7
publisher
Nature Publishing Group
external identifiers
  • Scopus:84962885566
  • WOS:000373289700001
ISSN
2041-1723
DOI
10.1038/ncomms11089
language
English
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yes
id
de8eb0d6-e480-44f2-b054-027dfeec337f
date added to LUP
2016-04-26 08:57:20
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2017-02-05 04:49:18
@article{de8eb0d6-e480-44f2-b054-027dfeec337f,
  abstract     = {<p>Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.</p>},
  articleno    = {11089},
  author       = {Bacos, Karl and Gillberg, Linn and Volkov, Petr and Olsson, Anders H and Hansen, Torben and Pedersen, Oluf and Gjesing, Anette Prior and Eiberg, Hans and Tuomi, Tiinamaija and Almgren, Peter and Groop, Leif and Eliasson, Lena and Vaag, Allan and Dayeh, Tasnim and Ling, Charlotte},
  issn         = {2041-1723},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes},
  url          = {http://dx.doi.org/10.1038/ncomms11089},
  volume       = {7},
  year         = {2016},
}