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 Marianne 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 Marianne Prior Gjesing, Hans Eiberg, Tiinamaija Tuomi, Peter Almgren, Leif Groop, Lena Eliasson, Allan Vaag, Tasnim Dayeh, Charlotte Ling

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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.

Original language	English
Article number	11089
Journal	Nature Communications
Volume	7
Number of pages	13
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms11089
Publication status	Published - 31 Mar 2016

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Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetesFinal published version, 736 KBLicence: CC BY

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Bacos, K., Gillberg, L., Volkov, P., Olsson, A. H., Hansen, T., Pedersen, O., Gjesing, A. M. 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, AMP , 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, 11089. https://doi.org/10.1038/ncomms11089

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

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.",

author = "Karl Bacos and Linn Gillberg and Petr Volkov and Olsson, {Anders H} and Torben Hansen and Oluf Pedersen and Gjesing, {Anette Marianne 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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doi = "10.1038/ncomms11089",

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T1 - Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

AU - Bacos, Karl

AU - Gillberg, Linn

AU - Volkov, Petr

AU - Olsson, Anders H

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Gjesing, Anette Marianne 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

Y1 - 2016/3/31

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.

U2 - 10.1038/ncomms11089

DO - 10.1038/ncomms11089

M3 - Journal article

C2 - 27029739

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11089

ER -

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

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