Jing Luan , Na Guo , Fengrui Hu , Xingchun Gou , Lixian Xu
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引用次数: 0
摘要
APPswe/PS1ΔE9小鼠是一种双转基因小鼠模型,它携带两种与阿尔茨海默病(AD)相关的突变蛋白的转基因。我们之前发现这种双转基因动物具有过早免疫衰老的表型。然而,目前还不清楚这种表型是如何发展到后期阶段的。本研究旨在阐明老年APPswe/PS1ΔE9小鼠与同窝对照野生型小鼠之间除与AD相关的系统特征外的变化。与对照野生型小鼠相比,24个月大的AD小鼠各器官肿瘤的发生率要高得多。此外,老年 AD 小鼠的存活率大大低于野生型对照小鼠。此外,我们发现这种表型差异主要是由严重的免疫老化引起的,与同龄的野生型小鼠相比,AD 小鼠中衰竭的 T 淋巴细胞比例较高就是证明。根据我们的研究结果,正常衰老产生的危害不如免疫衰老严重。与单纯的抗衰老相比,解决免疫衰老问题可能是实现无癌症长寿的更关键目标。
Aged AβPPswe/PS1ΔE9 mice as a useful animal model for studying the link between immunological senescence and diseases
The APPswe/PS1ΔE9 mouse is a double transgenic murine model that harbors two transgenes for Alzheimer's Disease (AD)-related mutant proteins. We previously discovered that this double transgenic animal had a premature immunosenescence phenotype. However, it is unclear how this phenotype progresses to a later stage. This study aimed to elucidate the changes in systemic characteristics aside from those associated with AD between elderly APPswe/PS1ΔE9 mice and littermate control wild-type mice. Tumors in all organs were considerably more frequent in AD mice aged 24 months than in the control wild-type mice. In addition, the survival rate of aged AD mice was considerably lower than that of wild-type control mice. Further, we discovered that the phenotypic difference was mainly caused by severe immunological aging, as evidenced by a high proportion of exhausted T lymphocytes in AD mice compared to wild-type mice of the same age. Based on our findings, the harm produced by normal aging is not as severe as immunological senescence. Addressing immunological aging, as opposed to anti-aging alone, may be a more crucial target for a long life free of cancer.
期刊介绍:
Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings.
Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.