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

Karl Bacos; Linn Gillberg; Petr Volkov; Anders H Olsson; Torben Hansen; Oluf Pedersen; Anette Prior Gjesing; Hans Eiberg; Tiinamaija Tuomi; Peter Almgren; Leif Groop; Lena Eliasson; Allan Vaag; Tasnim Dayeh; Charlotte Ling

doi:10.1038/ncomms11089

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

Karl Bacos, Linn Gillberg, Petr Volkov, Anders H Olsson, Torben Hansen, Oluf Pedersen, Anette Prior Gjesing, Hans Eiberg, Tiinamaija Tuomi, Peter Almgren, Leif Groop, Lena Eliasson, Allan Vaag, Tasnim Dayeh, Charlotte Ling

213 Citations (Scopus)

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 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.

Original language	English
Journal	Nature Communications
Volume	7
Pages (from-to)	11089
ISSN	2041-1722
DOIs	https://doi.org/10.1038/ncomms11089
Publication status	Published - 31 Mar 2016

Keywords

Adult
Age Factors
Aged
Biomarkers
DNA Methylation
Diabetes Mellitus, Type 2
Epigenomics
Gene Expression Regulation
Gene Silencing
Humans
Insulin
Islets of Langerhans
Middle Aged
Journal Article
Research Support, Non-U.S. Gov't

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Bacos, K., Gillberg, L., Volkov, P., Olsson, A. H., Hansen, T., Pedersen, O., Gjesing, A. P., Eiberg, H., Tuomi, T., Almgren, P., Groop, L., Eliasson, L., Vaag, A., Dayeh, T., & Ling, C. (2016). Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes. Nature Communications, 7, 11089. https://doi.org/10.1038/ncomms11089

Bacos, K, Gillberg, L, Volkov, P, Olsson, AH, Hansen, T, Pedersen, O, Gjesing, AP, Eiberg, H, Tuomi, T, Almgren, P, Groop, L, Eliasson, L, Vaag, A, Dayeh, T & Ling, C 2016, 'Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes', Nature Communications, vol. 7, pp. 11089. https://doi.org/10.1038/ncomms11089

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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 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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author = "Karl Bacos and Linn Gillberg and Petr Volkov and Olsson, \{Anders H\} and Torben Hansen and Oluf Pedersen and Gjesing, \{Anette Prior\} and Hans Eiberg and Tiinamaija Tuomi and Peter Almgren and Leif Groop and Lena Eliasson and Allan Vaag and Tasnim Dayeh and Charlotte Ling",

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AU - Bacos, Karl

AU - Gillberg, Linn

AU - Volkov, Petr

AU - Olsson, Anders H

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Gjesing, Anette Prior

AU - Eiberg, Hans

AU - Tuomi, Tiinamaija

AU - Almgren, Peter

AU - Groop, Leif

AU - Eliasson, Lena

AU - Vaag, Allan

AU - Dayeh, Tasnim

AU - Ling, Charlotte

PY - 2016/3/31

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N2 - 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.

AB - 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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KW - Age Factors

KW - Aged

KW - Biomarkers

KW - DNA Methylation

KW - Diabetes Mellitus, Type 2

KW - Epigenomics

KW - Gene Expression Regulation

KW - Gene Silencing

KW - Humans

KW - Insulin

KW - Islets of Langerhans

KW - Middle Aged

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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U2 - 10.1038/ncomms11089

DO - 10.1038/ncomms11089

M3 - Journal article

C2 - 27029739

SN - 2041-1722

VL - 7

SP - 11089

JO - Nature Communications

JF - Nature Communications

ER -

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

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Keywords

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