Department of Clinical Molecular Biology, Faculty of Medicine, University of Oslo, Oslo, Norway.
EpiGen, Akershus University Hospital, 1478, Lørenskog, Norway.
Biogerontology. 2019 Jun;20(3):255-269. doi: 10.1007/s10522-019-09798-2. Epub 2019 Jan 21.
Aging is a natural and unavoidable part of life. However, aging is also the primary driver of the dominant human diseases, such as cardiovascular disease, cancer, and neurodegenerative diseases, including Alzheimer's disease. Unraveling the sophisticated molecular mechanisms of the human aging process may provide novel strategies to extend 'healthy aging' and the cure of human aging-related diseases. Werner syndrome (WS), is a heritable human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. As a classical premature aging disease, etiological exploration of WS can shed light on the mechanisms of normal human aging and facilitate the development of interventional strategies to improve healthspan. Here, we summarize the latest progress of the molecular understandings of WRN protein, highlight the advantages of using different WS model systems, including Caenorhabditis elegans, Drosophila melanogaster and induced pluripotent stem cell (iPSC) systems. Further studies on WS will propel drug development for WS patients, and possibly also for normal age-related diseases.
衰老是生命的自然和不可避免的一部分。然而,衰老是导致心血管疾病、癌症和神经退行性疾病等主要人类疾病的主要驱动因素,包括阿尔茨海默病。揭示人类衰老过程的复杂分子机制可能为延长“健康衰老”和治疗与衰老相关的人类疾病提供新的策略。 Werner 综合征(WS)是一种遗传性人类早衰疾病,由编码 Werner(WRN)DNA 解旋酶的基因突变引起。作为一种经典的早衰疾病,对 WS 的病因探索可以揭示正常人类衰老的机制,并有助于开发改善健康寿命的干预策略。在这里,我们总结了对 WRN 蛋白的分子理解的最新进展,强调了使用不同的 WS 模型系统的优势,包括秀丽隐杆线虫、黑腹果蝇和诱导多能干细胞(iPSC)系统。对 WS 的进一步研究将推动 WS 患者的药物开发,也可能推动与正常年龄相关的疾病的药物开发。