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首页> 外文期刊>Ageing Research Reviews >DAMPs, ageing, and cancer: The 'DAMP Hypothesis'
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DAMPs, ageing, and cancer: The 'DAMP Hypothesis'

机译：潮湿，老化和癌症：'潮湿的假设'

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摘要

Ageing is a complex and multifactorial process characterized by the accumulation of many forms of damage at the molecular, cellular, and tissue level with advancing age. Ageing increases the risk of the onset of chronic inflammation-associated diseases such as cancer, diabetes, stroke, and neurodegenerative disease. In particular, ageing and cancer share some common origins and hallmarks such as genomic instability, epigenetic alteration, aberrant telomeres, inflammation and immune injury, reprogrammed metabolism, and degradation system impairment (including within the ubiquitin proteasome system and the autophagic machinery). Recent advances indicate that damage-associated molecular pattern molecules (DAMPS) such as high mobility group box 1, histones, S100, and heat shock proteins play location-dependent roles inside and outside the cell. These provide interaction platforms at molecular levels linked to common hallmarks of ageing and cancer. They can act as inducers, sensors, and mediators of stress through individual plasma membrane receptors, intracellular recognition receptors (e.g., advanced glycosylation end product-specific receptors, AIM2-like receptors, RIG-I-like receptors, and NOD1-like receptors, and toll-like receptors), or following endocytic uptake. Thus, the DAMP Hypothesis is novel and complements other theories that explain the features of ageing. DAMPs represent ideal biomarkers of ageing and provide an attractive target for interventions in ageing and age-associated diseases. (C) 2014 Elsevier B.V. All rights reserved.
机译：老化是一种复杂的和多学会过程，其特征在于分子，细胞和组织水平的多种形式的损伤的积累，具有推进年龄。老化增加了慢性炎症相关疾病，如癌症，糖尿病，中风和神经变性疾病的风险。特别是，老化和癌症具有一些常见的起源和标志，例如基因组不稳定性，表观遗传改革，异常端粒，炎症和免疫损伤，重编程的新陈代谢和降解系统损伤（包括在泛素蛋白酶体系和自噬机械中）。最近的预处理表明，损伤相关的分子图案分子（潮湿），例如高迁移率组盒1，组蛋白，S100和热休克蛋白在细胞内外呈现依赖性作用。这些提供了与衰老和癌症共同标志相关的分子水平的相互作用平台。它们可以作为诱导物，传感器和通过单个血浆膜受体，细胞内识别受体（例如，先进的糖基化最终产品特异性受体，Aim2样受体，钻石-i样受体，以及Nod1样受体的诱导剂，传感器和介质。和偶然的受体），或之后的内吞吸收。因此，潮湿的假设是新颖的，并补充了解释老化特征的其他理论。潮湿代表了衰老的理想生物标志物，并提供了衰老和年龄相关疾病的干预措施的吸引力。 （c）2014 Elsevier B.v.保留所有权利。

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