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Updated: Mar 6, 2026

Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
Published on: September 7, 2021
Single-cell aging trajectories reveal a dynamic coupling between nuclear size and proteasome concentration
Michael Mobaraki1,2, Changhui Deng1, Jiashun Zheng1
1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Proteostasis markers best predict yeast cell lifespan. Nuclear proteasome decline, linked to nuclear enlargement, may drive aging. This study offers insights into cellular aging mechanisms.
Area of Science:
- Cellular biology
- Aging research
- Systems biology
Background:
- Yeast replicative aging is a cell-autonomous process suitable for dynamic systems analysis.
- Understanding aging requires studying single-cell dynamics across various biological processes.
Purpose of the Study:
- To analyze dynamic trajectories of single yeast mother cells throughout their lifespan.
- To identify key predictors of individual cell lifespan.
- To investigate the role of nuclear dynamics in cellular aging.
Main Methods:
- Utilized an engineered yeast strain and a high-throughput microfluidic device.
- Monitored thousands of single yeast mother cells using fluorescent reporters.
- Applied mathematical modeling to analyze transport dynamics and nuclear size changes.
Main Results:
- Proteostasis markers were identified as the strongest predictors of individual cell lifespan.
- Observed distinct dynamics of proteasome concentration in the nucleus versus cytoplasm.
- Demonstrated a rapid decrease in nuclear proteasome concentration during aging, correlated with increasing nuclear size.
- Mathematical modeling supported the hypothesis that increased nuclear size affects factor transport.
Conclusions:
- Nuclear enlargement may contribute to aging by diluting essential nuclear factors.
- Single-cell dynamics data provide a resource for analyzing aging hallmarks.
- Proteostasis and nuclear dynamics are critical factors in yeast aging.
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