Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice.
Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice.
复制标题
小鼠海马衰老进程和抗衰老治疗分子网络的生物系统研究
DOI：
10.3389/fnagi.2017.00393
复制
发表时间：
2017
影响因子：
4.8
通讯作者：
Wen T
中科院分区：
文献类型：
--
作者：
Wang J;Li Q;Kong Y;Zhou F;Li J;Li W;Wang K;Wu T;Guan Y;Xie J;Wen T
衰老进程是一个人随着年龄的增长而遇到的过程，通常是随着时间的推移一系列正常生理变化的结果。导致老年人空间和情景记忆和学习能力丧失的海马体，在形态和分子水平上与衰老的有害影响密切相关。然而，与年龄相关的遗传改变在海马区的分子机制尚未得到很好的确立。为了对衰老过程有更深入的了解，我们重新分析了3月龄、24月龄和29个月龄小鼠的差异表达基因。结果显示，老年大鼠海马区大量免疫和炎症反应相关基因表达上调，膜受体相关基因表达下调。跨膜受体的下调可能表明老年人对环境暴露的感知较弱，因为许多跨膜蛋白参与了信号转导。此外，上调的免疫基因的分子相互作用分析表明，HUB基因Ywhae可能在衰老过程中的免疫和炎症反应中发挥重要作用，以及在海马体发育过程中发挥重要作用。我们的生物学实验证实了Ywhae及其伴侣在人和鼠之间的保守作用。此外，用人脐血血浆蛋白处理的高龄小鼠与磷酸盐缓冲盐水对照组之间的微阵列数据比较表明，促进高龄小鼠复兴的基因与衰老诱导的基因不同。这些结果表明，高龄小鼠的复兴不是一个简单的正常衰老进程的逆转过程。我们的数据指定了新的基因在衰老进程中的作用，并为未来探索衰老的潜在机制和抗衰老相关疾病治疗提供了进一步的理论依据。
Aging progression is a process that an individual encounters as they become older, and usually results from a series of normal physiological changes over time. The hippocampus, which contributes to the loss of spatial and episodic memory and learning in older people, is closely related to the detrimental effects of aging at the morphological and molecular levels. However, age-related genetic changes in hippocampal molecular mechanisms are not yet well-established. To provide additional insight into the aging process, differentially-expressed genes of 3- versus 24- and 29-month old mice were re-analyzed. The results revealed that a large number of immune and inflammatory response-related genes were up-regulated in the aged hippocampus, and membrane receptor-associated genes were down-regulated. The down-regulation of transmembrane receptors may indicate the weaker perception of environmental exposure in older people, since many transmembrane proteins participate in signal transduction. In addition, molecular interaction analysis of the up-regulated immune genes indicated that the hub gene, Ywhae, may play essential roles in immune and inflammatory responses during aging progression, as well as during hippocampal development. Our biological experiments confirmed the conserved roles of Ywhae and its partners between human and mouse. Furthermore, comparison of microarray data between advanced-age mice treated with human umbilical cord blood plasma protein and the phosphate-buffered saline control showed that the genes that contribute to the revitalization of advanced-age mice are different from the genes induced by aging. These results implied that the revitalization of advanced-age mice is not a simple reverse process of normal aging progression. Our data assigned novel roles of genes during aging progression and provided further theoretic evidence for future studies exploring the underlying mechanisms of aging and anti-aging-related disease therapy.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Chatr-Aryamontri A;Oughtred R;Boucher L;Rust J;Chang C;Kolas NK;O'Donnell L;Oster S;Theesfeld C;Sellam A;Stark C;Breitkreutz BJ;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
3.3
作者：
Baxter, HC;Liu, WG;Fraser, JR
通讯作者：
Fraser, JR
影响因子：
3.8
作者：
Begley, L. A.;Kasina, S.;Macoska, J. A.
通讯作者：
Macoska, J. A.
影响因子：
7.1
作者：
Conroy, Paula M.;O'Sullivan, Maurice G.;Kerry, Joseph P.
通讯作者：
Kerry, Joseph P.