Genome-wide screens in yeast models towards understanding chronological lifespan regulation

Abstract

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.

Sporulation: A response to starvation in the fission yeast Schizosaccharomyces pombe

“…CLS is defined as the duration of survival of nondividing cells. In yeast, the survival rate after entry into the stationary phase is measured as the CLS (Kurauchi et al, 2017 ; Legon & Rallis, 2022 ; Lin & Austriaco, 2014 ; Longo et al, 2012 ; Matsui et al, 2021 ; Roux et al, 2010 ). At least 100 genes, 30 drugs, and approximately 10 nutritional conditions have extended the CLS in S. pombe (Emami & Ueno, 2021 ; Fujita et al, 2007 ; Hibi et al, 2018 ; Imai et al, 2020 ; Naito et al, 2014 ; Ohtsuka et al, 2021c ; Romila et al, 2021 ; Su et al, 1996 ; Takuma et al, 2013 ).…”

The continuing evolution of barcode applications: Functional toxicology to cell lineage

“…32 These pooled collections can then be screened for genes that confer resistance or sensitivity to antibiotics, pharmaceuticals, toxicants, nutrients, temperature (heat or cold shock), hypoxia, oxidative species, and other environmental conditions. [33][34][35][36] The advantage of using the model eukaryotes S. pombe and budding yeast are that many genes are orthologous to higher eukaryotic cells; indeed Kachroo et al 37 demonstrated that many essential genes could be replaced by the corresponding human gene and restore function. These screens are even more important now considering that 42 billion pounds of chemicals are produced or imported into the United States of America daily.…”

Response to leucine in Schizosaccharomyces pombe (fission yeast)

“… 2013 , Hibi et al . 2018 , Legon and Rallis 2021 ). More than 100 genes have been reported to be involved in the lifespan extension, more than 30 drugs extend the lifespan, and starvation of various types of nutrients extend the lifespan in S. pombe (Matsui et al .…”