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A molecular mechanism of chronological aging in yeast.

ABSTRACT: The molecular mechanisms that cause organismal aging are a topic of intense scrutiny and debate. Dietary restriction extends the life span of many organisms, including yeast, and efforts are underway to understand the biochemical and genetic pathways that regulate this life span extension in model organisms. Here we describe the mechanism by which dietary restriction extends yeast chronological life span, defined as the length of time stationary yeast cells remain viable in a quiescent state. We find that aging under standard culture conditions is the result of a cell-extrinsic component that is linked to the pH of the culture medium. We identify acetic acid as a cell-extrinsic mediator of cell death during chronological aging, and demonstrate that dietary restriction, growth in a non-fermentable carbon source, or transferring cells to water increases chronological life span by reducing or eliminating extracellular acetic acid. Other life span extending environmental and genetic interventions, such as growth in high osmolarity media, deletion of SCH9 or RAS2, increase cellular resistance to acetic acid. We conclude that acetic acid induced mortality is the primary mechanism of chronological aging in yeast under standard conditions.

SUBMITTER: Burtner CR

PROVIDER: S-EPMC2746416 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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A molecular mechanism of chronological aging in yeast.

Burtner Christopher R CR Murakami Christopher J CJ Kennedy Brian K BK Kaeberlein Matt M

Cell cycle (Georgetown, Tex.) 20090423 8

The molecular mechanisms that cause organismal aging are a topic of intense scrutiny and debate. Dietary restriction extends the life span of many organisms, including yeast, and efforts are underway to understand the biochemical and genetic pathways that regulate this life span extension in model organisms. Here we describe the mechanism by which dietary restriction extends yeast chronological life span, defined as the length of time stationary yeast cells remain viable in a quiescent state. We ...[more]

PMID: 19305133

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Project description:Purpose: To gain additional insights to candidate factors promoting longevity in Caloric Restricted Conditioned Media (CRCM), we performed transcriptomics analysis (RNA-seq) on BY4741 yeast cells grown in non-restricted SC media supplemented with CRCM, Non-restricted Conditioned Media (NRCM), or water as a control with a goal of identifying physiological responses that could be linked to specific metabolites. Methods: RNA profiles of NR (SC, 2% glucose) treated cells supplemented with water, 2% CRCM, or 2% NRCM at log phase, 24, and 96 hours post-inoculation. These samples were conducted in triplicate. Following inoculation, we harvested cells at log phase, 24 hrs (late diauxic shift), and 96 hrs (stationary phase).Total RNA was isolated using the hot acid phenol method and then processed into Illumina DNA sequencing libraries. Briefly, total RNA was treated with DNase I for 10 min at 37°C and then measured for concentration and quality with an Agilent Bioanalyzer. PolyA mRNA selection was performed on 5µg of the DNase-treated total RNA with the NEBNext Poly(A) mRNA magnetic isolation module (E7490). DNA sequencing libraries were then generated with the NEBNExt Ultra Directional RNA library Prep kit for Illumina (E7420). Libraries were sequenced on an Illumina NextSeq 500 by the UVA Genome Analysis and Technology Core. Results: Sequencing reads were mapped to the sacCer3 genome using bowtie2 with default settings. We preprocessed sequencing data from the UVA genomics core and analyzed differential gene expression in R using DESeq2. We found that In log phase cells, there were no significantly upregulated or downregulated genes in the CRCM or NRCM samples as compared to the water supplemented control (FDR <0.05). At the 24 hr timepoint, CRCM samples diverged from the NRCM and water supplemented control samples, and showed many more differentially regulated genes than the NRCM-treated samples. At the 96 hr timepoint, NRCM samples also became more clearly separated from the control in a PCA plot , though there were still a large number of genes exclusively altered in the CRCM samples. Furthermore, the YCL064C (CHA1) gene clearly stood out as being the most significantly upregulated in conditioned media supplementation. Conclusions: RNAseq data led us to explore YCL064C (CHA1) gene clearly stood out as being the most significantly upregulated in the conditioned media experiments. CHA1 encodes a predominantly mitochondrial L-serine (L-threonine) deaminase that catabolizes these amino acids. RNA-seq based transcriptome analysis allowed us to explore L-serine contribution to longevity phenotype we observed with CRCM.

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A molecular mechanism of chronological aging in yeast.

Publications

A molecular mechanism of chronological aging in yeast.

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