AI Article Synopsis
- Aging affects cellular functions, particularly the regulation of protein breakdown, with efficient proteasome activity linked to longer lifespans in rodents and decreased function associated with aging.
- The ubiquitin proteasome system (UPS) is crucial for clearing unwanted proteins, and enhancing proteasome activity through small molecule stimulators may combat cellular stress from protein buildup.
- The study developed methods to test the effects of proteasome stimulators on yeast, assessing their potential to extend lifespan and improve protein degradation in both normal and proteasome-deficient yeast strains.
Article Abstract
Aging is characterized by changes in several cellular processes, including dysregulation of proteostasis. Current research has shown long-lived rodents display elevated proteasome activity throughout life and proteasome dysfunction is linked to shorter lifespans in a transgenic mouse model. The ubiquitin proteasome system (UPS) is one of the main pathways leading to cellular protein clearance and quality maintenance. Reduction in proteasome activity is associated with aging and its related pathologies. Small molecule stimulators of the proteasome have been proposed to help alleviate cellular stress related to unwanted protein accumulation. Here we have described the development of techniques to monitor the impact of proteasome stimulation in wild-type yeast and a strain that has impaired proteasome expression. We validated our chronological lifespan assay using both types of yeast with a variety of small molecule stimulators at different concentrations. By modifying the media conditions for the yeast, molecules can be evaluated for their potential to increase chronological lifespan in five days. Additionally, our assay conditions can be used to monitor the activity of proteasome stimulators in modulating the degradation of a YFP-α-synuclein fusion protein produced by yeast. We anticipate these methods to be valuable for those wishing to study the impact of increasing proteasome-mediated degradation of proteins in a eukaryotic model organism.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478123 | PMC |
| http://dx.doi.org/10.1002/cbic.202100117 | DOI Listing |
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