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心脏衰老的基因操控

Genetic manipulation of cardiac ageing.

作者信息

Cannon Leah, Bodmer Rolf

机构信息

Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.

出版信息

J Physiol. 2016 Apr 15;594(8):2075-83. doi: 10.1113/JP270563. Epub 2015 Jul 14.

Abstract

Ageing in humans is associated with a significant increase in the prevalence of cardiovascular disease. We still do not fully understand the molecular mechanisms underpinning this correlation. However, a number of insights into which genes control cardiac ageing have come from studying hearts of the fruit fly, Drosophila melanogaster. The fly's simple heart tube has similar molecular structure and basic physiology to the human heart. Also, both fly and human hearts experience significant age-related morphological and functional decline. Studies on the fly heart have highlighted the involvement of key nutrient sensing, ion channel and sarcomeric genes in cardiac ageing. Many of these genes have also been implicated in ageing of the mammalian heart. Genes that increase oxidative stress, or are linked to cardiac hypertrophy or neurodegenerative diseases in mammals also affect cardiac ageing in the fruit fly. Moreover, fly studies have demonstrated the potential of exercise and statins to treat age-related cardiac disease. These results show the value of Drosophila as a model to discover the genetic causes of human cardiac ageing.

摘要

人类衰老与心血管疾病患病率的显著增加有关。我们仍未完全理解这种关联背后的分子机制。然而,通过研究果蝇(黑腹果蝇)的心脏,我们对哪些基因控制心脏衰老有了一些认识。果蝇简单的心脏管在分子结构和基本生理功能上与人类心脏相似。此外,果蝇和人类的心脏都会经历与年龄相关的显著形态和功能衰退。对果蝇心脏的研究突出了关键营养感知、离子通道和肌节基因在心脏衰老中的作用。其中许多基因也与哺乳动物心脏衰老有关。在哺乳动物中增加氧化应激、或与心脏肥大或神经退行性疾病相关的基因,也会影响果蝇的心脏衰老。此外,果蝇研究已经证明了运动和他汀类药物治疗与年龄相关心脏病的潜力。这些结果表明果蝇作为发现人类心脏衰老遗传原因模型的价值。

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