Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.
Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.
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DOI：
10.1038/ncomms11089
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发表时间：
2016-03-31
影响因子：
16.6
通讯作者：
Ling C
中科院分区：
文献类型：
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作者：
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
衰老与胰岛功能受损和2型糖尿病（T2 D）风险增加有关。在这里，我们研究了年龄相关的表观遗传变化是否影响人类胰岛功能，以及基于血液的表观遗传生物标志物是否反映了这些变化并与未来的T2 D相关。我们分析了来自87名年龄在26-74岁之间的非糖尿病供体的胰岛中的全基因组DNA甲基化。衰老与241个位点的DNA甲基化增加有关。这些位点覆盖先前与T2 D相关的基因座，例如KLF 14。基于血液的表观遗传生物标志物反映了在人类胰岛中鉴定的83个基因（例如，KLF 14，FHL 2，ZNF 518 B和FAM 123 C）中与年龄相关的甲基化变化，其中一些与胰岛素分泌和T2 D相关。DNA甲基化与多个基因的胰岛表达相关，包括FHL 2、ZNF 518 B、GNPNAT 1和HLTF。在β细胞中沉默这些基因会改变胰岛素分泌。总之，我们证明了基于血液的表观遗传生物标志物反映了人类胰岛中与年龄相关的DNA甲基化变化，并与体内胰岛素分泌和T2 D相关。 衰老与胰岛功能受损、2型糖尿病风险增加和DNA甲基化变化有关。在这里，作者发现了基于血液的生物标志物，反映了与胰岛素分泌和糖尿病相关的人类胰岛中与年龄相关的DNA甲基化变化。
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. Aging is associated with impaired pancreatic islet function, increased risk of type 2 diabetes, and changes in DNA methylation. Here the authors find blood-based biomarkers that reflect age-associated DNA methylation changes in human pancreatic islets associated with insulin secretion and diabetes.