Stress induced aging in mouse eye.
Stress induced aging in mouse eye.
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衰老是一个影响生物体中所有细胞的普遍过程，是一组称为青光眼的神经病的主要风险因素，其中眼内压升高是影响组织的已知压力之一。我们对衰老对视网膜应激反应的分子影响的理解非常有限;因此，我们开发了一种新的小鼠模型来实验性地解决这个问题。在这里，我们表明，敏感性的压力反应随着年龄的增长，并启动染色质水平。我们证明，高眼压激活的应激反应，这是类似于自然衰老，并涉及炎症和衰老的激活。我们发现，多种情况下的压力升高导致年轻的视网膜老化的转录和DNA甲基化水平上测量，并伴随着局部组蛋白修饰的变化。我们的数据表明，反复的压力加速组织中衰老特征的出现，并表明染色质修饰是衰老的关键分子组成部分。最后，我们的工作进一步强调了早期诊断和预防以及年龄相关疾病（包括青光眼）的年龄特异性管理的重要性。Skowronska-Krawczyk及其同事描述了衰老视网膜中发生的转录和表观遗传变化。他们还表明，在眼睛眼内压升高等压力下，视网膜组织会发生类似于自然衰老的表观遗传和转录变化。最后，他们证明，在重复压力下，年轻的视网膜显示出加速老化的特征，可以使用无偏的方法（如DNA甲基化时钟）来测量。
Aging, a universal process that affects all cells in an organism, is a major risk factor for a group of neuropathies called glaucoma, where elevated intraocular pressure is one of the known stresses affecting the tissue. Our understanding of molecular impact of aging on response to stress in retina is very limited; therefore, we developed a new mouse model to approach this question experimentally. Here we show that susceptibility to response to stress increases with age and is primed on chromatin level. We demonstrate that ocular hypertension activates a stress response that is similar to natural aging and involves activation of inflammation and senescence. We show that multiple instances of pressure elevation cause aging of young retina as measured on transcriptional and DNA methylation level and are accompanied by local histone modification changes. Our data show that repeated stress accelerates appearance of aging features in tissues and suggest chromatin modifications as the key molecular components of aging. Lastly, our work further emphasizes the importance of early diagnosis and prevention as well as age‐specific management of age‐related diseases, including glaucoma. Skowronska‐Krawczyk and colleagues describe the transcriptional and epigenetic changes happening in aging retina. They also show that upon stress such as intraocular pressure elevation in the eye, retinal tissue undergoes epigenetic and transcriptional changes similar to natural aging. Finally, they demonstrate that upon repetitive stress young retina shows features of accelerated aging that can be measured using unbiased methods such as DNA methylation clock.
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全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
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Zhang, Kang
影响因子：
64.8
作者：
Lu Y;Brommer B;Tian X;Krishnan A;Meer M;Wang C;Vera DL;Zeng Q;Yu D;Bonkowski MS;Yang JH;Zhou S;Hoffmann EM;Karg MM;Schultz MB;Kane AE;Davidsohn N;Korobkina E;Chwalek K;Rajman LA;Church GM;Hochedlinger K;Gladyshev VN;Horvath S;Levine ME;Gregory-Ksander MS;Ksander BR;He Z;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
17.8
作者：
Aptel, Florent;Weinreb, Robert N.;Mansouri, Kaweh
通讯作者：
Mansouri, Kaweh
影响因子：
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作者：
Boeva V
通讯作者：
Boeva V
哺乳动物甲基化阵列，用于在保守序列上分析甲基化水平。
影响因子：
16.6
作者：
Arneson A;Haghani A;Thompson MJ;Pellegrini M;Kwon SB;Vu H;Maciejewski E;Yao M;Li CZ;Lu AT;Morselli M;Rubbi L;Barnes B;Hansen KD;Zhou W;Breeze CE;Ernst J;Horvath S
通讯作者：
Horvath S