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Updated: May 29, 2026
10:39
A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
Published on: September 17, 2020
Elevated proteasome capacity extends replicative lifespan in Saccharomyces cerevisiae.
Undine Kruegel1, Brett Robison, Thomas Dange
1Department of Biochemistry, Albert Einstein College of Medicine, New York, New York, United States of America.
Plos Genetics
|September 21, 2011
Summary
Enhancing the ubiquitin/proteasome system (UPS) capacity in yeast significantly extends lifespan and stress resistance. This longevity is linked to improved clearance of damaged proteins, independent of oxidative stress responses.
Area of Science:
- Cellular Biology
- Aging Research
- Molecular Biology
Background:
- Cellular aging involves accumulating molecular damage due to impaired repair and elimination.
- The ubiquitin/proteasome system (UPS) is crucial for clearing toxic protein aggregates.
- Previous studies suggest a link between proteasome function and longevity.
Purpose of the Study:
- To investigate the direct impact of proteasome function on aging and lifespan in yeast.
- To establish a method for modulating UPS capacity.
Main Methods:
- Manipulated levels of the transcription factor Rpn4 to alter UPS capacity.
- Assessed replicative lifespan (RLS) and resistance to proteotoxic stress.
- Performed epistasis analyses with known longevity pathways.
Main Results:
- Increased UPS capacity, via elevated Rpn4, significantly enhanced yeast RLS and proteotoxic stress resistance.
- Reduced UPS capacity had opposite effects.
- Lifespan extension was independent of oxidative stress response pathways (Yap1).
- Enhanced UPS capacity improved clearance of toxic huntingtin fragments.
Conclusions:
- UPS capacity is a key determinant of yeast replicative lifespan.
- Proteasome-mediated lifespan extension is distinct from dietary restriction, Tor1, and Sir2 pathways.
- Promoting proteasome function may offer therapeutic benefits for age-related diseases.
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