Role of NF-κB in Ageing and Age-Related Diseases: Lessons from Genetically Modified Mouse Models.
Role of NF-κB in Ageing and Age-Related Diseases: Lessons from Genetically Modified Mouse Models.
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DOI：
10.3390/cells10081906
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发表时间：
2021-07-27
期刊：
影响因子：
6
通讯作者：
Casanova ML
中科院分区：
文献类型：
--
作者：
García-García VA;Alameda JP;Page A;Casanova ML
衰老是一个复杂的过程，由遗传、表观遗传和环境因素的多方面相互作用引起。它表现为生物体生理功能的下降，并与年龄相关的慢性疾病和癌症的发展有关。人们认为衰老遵循严格调控的程序，其中一些信号通路对衰老状态的建立和维持至关重要。慢性炎症是促进生物衰老过程和合并症的主要机制，其中转录因子 NF-κB（活化 B 细胞的核因子 kappa 轻链增强子）是炎症反应的关键介质。再加上发现 NF-κB 的激活或抑制可以分别诱导或逆转衰老生物体的主要特征，因此人们将其视为衰老驱动因素的关键转录因子。在这篇综述中，我们重点关注完全通过生成涉及 NF-κB 信号通路的任一蛋白质的敲除和转基因小鼠模型获得的数据，这些模型提供了有关控制衰老的复杂过程或分子机制的相关信息。我们回顾了NF-κB与早衰的关系；与衰老相关的癌症的发展以及 NF-κB 激活在与年龄相关的疾病发展中的影响，其中一些疾病大大增加了患癌症的风险。
Ageing is a complex process, induced by multifaceted interaction of genetic, epigenetic, and environmental factors. It is manifested by a decline in the physiological functions of organisms and associated to the development of age-related chronic diseases and cancer development. It is considered that ageing follows a strictly-regulated program, in which some signaling pathways critically contribute to the establishment and maintenance of the aged state. Chronic inflammation is a major mechanism that promotes the biological ageing process and comorbidity, with the transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) as a crucial mediator of inflammatory responses. This, together with the finding that the activation or inhibition of NF-κB can induce or reverse respectively the main features of aged organisms, has brought it under consideration as a key transcription factor that acts as a driver of ageing. In this review, we focused on the data obtained entirely through the generation of knockout and transgenic mouse models of either protein involved in the NF-κB signaling pathway that have provided relevant information about the intricate processes or molecular mechanisms that control ageing. We have reviewed the relationship of NF-κB and premature ageing; the development of cancer associated with ageing and the implication of NF-κB activation in the development of age-related diseases, some of which greatly increase the risk of developing cancer.
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影响因子：
2.5
作者：
Bhatt BA;Dedousis N;Sipula IJ;O'Doherty RM
通讯作者：
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DOI：
10.1146/annurev-pathol-121808-102144
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Annual review of pathology
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