Zierer Jonas, Menni Cristina, Kastenmüller Gabi, Spector Tim D
Department of Twins Research and Genetic Epidemiology, Kings College London, London, United Kingdom.
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Aging Cell. 2015 Dec;14(6):933-44. doi: 10.1111/acel.12386. Epub 2015 Aug 30.
Age is the strongest risk factor for many diseases including neurodegenerative disorders, coronary heart disease, type 2 diabetes and cancer. Due to increasing life expectancy and low birth rates, the incidence of age-related diseases is increasing in industrialized countries. Therefore, understanding the relationship between diseases and aging and facilitating healthy aging are major goals in medical research. In the last decades, the dimension of biological data has drastically increased with high-throughput technologies now measuring thousands of (epi) genetic, expression and metabolic variables. The most common and so far successful approach to the analysis of these data is the so-called reductionist approach. It consists of separately testing each variable for association with the phenotype of interest such as age or age-related disease. However, a large portion of the observed phenotypic variance remains unexplained and a comprehensive understanding of most complex phenotypes is lacking. Systems biology aims to integrate data from different experiments to gain an understanding of the system as a whole rather than focusing on individual factors. It thus allows deeper insights into the mechanisms of complex traits, which are caused by the joint influence of several, interacting changes in the biological system. In this review, we look at the current progress of applying omics technologies to identify biomarkers of aging. We then survey existing systems biology approaches that allow for an integration of different types of data and highlight the need for further developments in this area to improve epidemiologic investigations.
年龄是许多疾病(包括神经退行性疾病、冠心病、2型糖尿病和癌症)最强的风险因素。由于预期寿命延长和出生率降低,工业化国家与年龄相关疾病的发病率正在上升。因此,了解疾病与衰老之间的关系并促进健康衰老是医学研究的主要目标。在过去几十年中,随着高通量技术现在能够测量数千个(表观)遗传、表达和代谢变量,生物数据的规模急剧增加。分析这些数据最常见且迄今为止最成功的方法是所谓的还原论方法。它包括分别测试每个变量与感兴趣的表型(如年龄或与年龄相关的疾病)的关联。然而,很大一部分观察到的表型变异仍无法解释,并且缺乏对最复杂表型的全面理解。系统生物学旨在整合来自不同实验的数据,以获得对整个系统的理解,而不是专注于个别因素。因此,它能够更深入地洞察复杂性状的机制,这些机制是由生物系统中几个相互作用的变化共同影响引起的。在这篇综述中,我们审视了应用组学技术识别衰老生物标志物的当前进展。然后,我们调查了现有的系统生物学方法,这些方法允许整合不同类型的数据,并强调该领域进一步发展以改善流行病学调查的必要性。