Bloom syndrome patients and mice display accelerated epigenetic aging.
Bloom syndrome patients and mice display accelerated epigenetic aging.
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布卢姆综合征 (BSyn) 是一种由 BLM 基因变异引起的常染色体隐性遗传疾病，该基因与基因组稳定性有关。 BSyn 患者表现出生长不良、阳光敏感、轻度免疫缺陷、糖尿病和癌症（最常见的是白血病）风险增加。有趣的是，BSyn 患者没有其他过早衰老的迹象，例如早期进行性脱发和白内障。我们着手确定 BSyn 中的表观遗传年龄，这可以比实际年龄更好地预测健康和疾病。我们的结果首次表明，与携带者相比，BSyn 患者在血液淋巴细胞的多项指标上有加速表观遗传衰老的证据。此外，根据大脑甲基化时钟，纯合 Blm 小鼠在多个组织中表现出加速的甲基化年龄，包括大脑、血液、肾脏、心脏和皮肤。总体而言，我们发现 Bloom 综合征与多个组织中加速的表观遗传衰老效应相关，更普遍的是对 CpG 甲基化水平的强烈影响。布卢姆综合征是一种常染色体隐性遗传病，由称为 BLM 的 DNA 修复基因种系变异引起。布卢姆综合症患者患癌症的风险增加，并且具有加速衰老的多种特征。我们证明，与携带者相比，布卢姆综合征患者的表观遗传衰老加快，并且布卢姆综合征的小鼠模型也显示出以时钟和组织特异性方式加速表观遗传衰老的特征。
Bloom syndrome (BSyn) is an autosomal recessive disorder caused by variants in the BLM gene, which is involved in genome stability. Patients with BSyn present with poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased risk of cancer, most commonly leukemias. Interestingly, patients with BSyn do not have other signs of premature aging such as early, progressive hair loss and cataracts. We set out to determine epigenetic age in BSyn, which can be a better predictor of health and disease over chronological age. Our results show for the first time that patients with BSyn have evidence of accelerated epigenetic aging across several measures in blood lymphocytes, as compared to carriers. Additionally, homozygous Blm mice exhibit accelerated methylation age in multiple tissues, including brain, blood, kidney, heart, and skin, according to the brain methylation clock. Overall, we find that Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and more generally a strong effect on CpG methylation levels. Bloom syndrome is an autosomal recessive disorder caused by germline variants in a DNA repair gene called BLM. Patients with Bloom Syndrome have increased risk of cancer and variable features of accelerated aging. We demonstrate that Bloom Syndrome patients have increased epigenetic aging compared to carriers and that a mouse model of Bloom also shows features of accelerated epigenetic aging in a clock‐ and tissue‐specific manner.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1093/bioinformatics/btac745
发表时间：
2023-01-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
通讯作者：
--
影响因子：
0.5
作者：
Aljarad, Sara;Alhamid, Ahmad;Aziz, Ghasan
通讯作者：
Aziz, Ghasan
影响因子：
14.9
作者：
Daley JM;Chiba T;Xue X;Niu H;Sung P
通讯作者：
Sung P
影响因子：
2
作者：
Chen CL;Yang JS;Zhang X;Tian T;Zeng R;Zhang GH;Jia XG
通讯作者：
Jia XG