Sis2 regulates yeast replicative lifespan in a dose-dependent manner.

Area of Science:

• * Molecular Biology
• * Genetics
• * Aging Research

Background:

• * Microfluidic platforms enable high-precision measurements of yeast replicative lifespan (RLS).
• * Comparative quantification of RLS across large strain libraries has been lacking.
• * Previous studies reported extended lifespans for various gene-deleted yeast strains.

Purpose of the Study:

• * To conduct a high-precision, comparative quantification of RLS across 307 single-gene-deleted yeast strains.
• * To identify gene deletions that significantly alter yeast lifespan and validate previous findings.
• * To investigate the role of the SIS2 gene and its associated pathways in lifespan regulation.

Main Methods:

• * Microfluidic measurement of RLS for 307 yeast strains, each with a single gene deletion.
• * Comparative analysis of RLS against wild-type strains.
• * RNA-sequencing (RNA-seq) to analyze transcriptional changes in the SIS2 deletion mutant.
• * Functional analysis involving the introduction of the human PPCDC gene.

Main Results:

• * 56% of tested gene-deleted strains did not exhibit extended RLS compared to wild-type.
• * 44% of strains showed extended RLS, but the degree of extension often differed from prior reports.
• * Deletion of the SIS2 gene resulted in the most significant RLS increase, demonstrating a dose-dependent effect.
• * The human PPCDC gene neutralized the lifespan extension in the sis2Δ background.
• * RNA-seq revealed increased transcription of cell-cycle machinery components in the sis2Δ strain.

Conclusions:

• * High-precision microfluidic measurement is crucial for accurate yeast lifespan studies, revealing discrepancies with previous findings.
• * The SIS2 gene plays a significant role in yeast lifespan regulation, potentially through the coenzyme A biosynthesis pathway.
• * Cell-cycle regulation is implicated in the lifespan extension observed in sis2Δ mutants.
• * Further elucidation of the gene network governing lifespan requires precise measurement techniques.