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Updated: Nov 28, 2025
08:52
Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry
Published on: April 6, 2022
3.8K
Cellular proteostasis decline in human senescence
Niv Sabath1, Flonia Levy-Adam1, Amal Younis1
1Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 31096 Haifa, Israel.
Summary
Proteostasis decline, crucial for aging in worms, is also intrinsic to human aging. Senescent human cells struggle to activate stress responses, impairing protein homeostasis and aging.
Area of Science:
- Cellular Biology
- Aging Research
- Molecular Biology
Background:
- Proteostasis collapse is a hallmark of nematode aging.
- Its occurrence in human senescence remained unclear.
Purpose of the Study:
- To investigate proteostasis decline in human senescence.
- To characterize molecular mechanisms underlying this decline.
Main Methods:
- Transcriptome-wide analysis of gene expression, splicing, and translation.
- Assessment of heat shock response and unfolded protein response (UPR) pathways.
- Analysis of HSF1 and ATF6 localization.
- Evaluation of proteasome function.
Main Results:
- Senescent cells exhibit impaired transcriptional activation of heat shock response.
- HSF1 nuclear localization and distribution are diminished in senescence.
- UPR shows a decoupling, with enhanced translation but impaired transcriptional response.
- ATF6 nuclear localization is reduced, and proteasome function is impaired in stressed senescent cells.
Conclusions:
- Human senescence involves intrinsic proteostasis decline.
- Deterioration in mounting dynamic stress transcriptional programs impacts proteostasis.
- This decline is linked to human aging and impaired cellular stress responses.
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