Brief Funct Genomics. 2022 Jan 25;21(1):4-12. doi: 10.1093/bfgp/elab011.
Cellular models such as yeasts are a driving force in biogerontology studies. Their simpler genome, short lifespans and vast genetic and genomics resources make them ideal to characterise pro-ageing and anti-ageing genes and signalling pathways. Over the last three decades, yeasts have contributed to the understanding of fundamental aspects of lifespan regulation including the roles of nutrient response, global protein translation rates and quality, DNA damage, oxidative stress, mitochondrial function and dysfunction as well as autophagy. In this short review, we focus on approaches used for competitive and non-competitive cell-based screens using the budding yeast Saccharomyces cerevisiae, and the fission yeast Schizosaccharomyces pombe, for deciphering the molecular mechanisms underlying chronological ageing. Automation accompanied with appropriate computational tools allowed manipulation of hundreds of thousands of colonies, generation, processing and analysis of genome-wide lifespan data. Together with barcoding and modern mutagenesis technologies, these approaches have allowed to take decisive steps towards a global, comprehensive view of cellular ageing.
细胞模型(如酵母)是生物衰老学研究的主要动力。它们的基因组相对简单、寿命较短,并且拥有丰富的遗传和基因组资源,这使它们成为研究衰老促进和抗衰老基因以及信号通路的理想模型。在过去的三十年中,酵母为理解寿命调控的基本方面做出了贡献,包括营养响应、全局蛋白质翻译率和质量、DNA 损伤、氧化应激、线粒体功能和失调以及自噬的作用。在这篇简短的综述中,我们重点介绍了使用芽殖酵母酿酒酵母和裂殖酵母 Schizosaccharomyces pombe 进行基于细胞的竞争和非竞争筛选的方法,以揭示程序性衰老的分子机制。自动化与适当的计算工具相结合,允许对数十万菌落进行操作,生成、处理和分析全基因组寿命数据。结合条形码和现代诱变技术,这些方法已经朝着全面、综合的细胞衰老观迈出了决定性的一步。