rDNA array length is a major determinant of replicative lifespan in budding yeast

Area of Science:

• Gerontology
• Molecular Biology
• Yeast Genetics

Background:

• Aging and lifespan regulation are complex and not fully understood.
• Budding yeast serves as a model organism for aging research.
• Ribosomal DNA (rDNA) plays a crucial role in cellular function and aging.

Purpose of the Study:

• To investigate the relationship between ribosomal DNA copy number (rDNA CN) and replicative lifespan (RLS) in budding yeast.
• To elucidate the mechanisms linking rDNA CN to RLS.
• To assess the impact of rDNA CN on lifespan-modifying mutations.

Main Methods:

• Analysis of rDNA CN and RLS in wild-type and mutant budding yeast strains.
• Measurement of SIR2 expression levels.
• Quantification of extrachromosomal rDNA circle (ERC) accumulation.
• Genetic manipulation, including FOB1 deletion.

Main Results:

• A positive correlation was found between rDNA CN and RLS, explaining over 70% of RLS variability.
• Low rDNA CN was associated with attenuated SIR2 expression and increased ERC accumulation, resulting in shorter RLS.
• Deletion of FOB1 abolished the relationship between rDNA CN and RLS by suppressing ERC formation.
• Lifespan-enhancing mutations showed significant dependence on rDNA CN.

Conclusions:

• rDNA CN is a critical determinant of RLS in budding yeast.
• Mechanisms regulating rDNA CN, such as SIR2 and FOB1/ERC, influence lifespan.
• Environmental and genetic factors modulating rDNA CN must be considered for accurate lifespan interpretation.