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Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
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NFκB dynamics-dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence
Sho Tabata1, Keita Matsuda1, Shou Soeda1
1Laboratory for Cell Systems, Institute for Protein Research, Osaka University, Suita, Japan.
The FEBS Journal
|July 16, 2024
Summary
Altering nuclear factor κB (NFκB) signaling dynamics by depleting NFκB inhibitor alpha (IκBα) promotes cellular senescence. This sustained NFκB activity drives inflammation and aging, impacting gene expression and cell cycle progression.
Area of Science:
- Cellular Biology
- Molecular Biology
- Aging Research
Background:
- Nuclear factor κB (NFκB) signaling is upregulated in aging and linked to chronic inflammation.
- The precise role of NFκB dynamics in cellular senescence has remained unclear.
Purpose of the Study:
- To investigate how alterations in NFκB nuclear dynamics influence cellular senescence.
- To explore the role of NFκB inhibitor alpha (IκBα) in regulating NFκB activity and senescence.
Main Methods:
- Depletion of IκBα in the presence of tumor necrosis factor α (TNFα) to alter NFκB nuclear dynamics.
- Assessing NFκB-DNA binding, inflammatory gene expression, and cell cycle progression.
- Measuring IκBα protein levels under replicative and oxidative stress in vitro.
- Analyzing IκBα protein and NFκB-DNA binding in aged mouse hearts.
Main Results:
- Sustained NFκB activity, induced by IκBα depletion, promoted cellular senescence.
- Enhanced inflammatory gene expression and slowed cell cycle were observed with sustained NFκB.
- IκBα protein decreased under replicative and oxidative stress.
- Aged mouse hearts showed decreased IκBα and increased NFκB-DNA binding at age-associated gene loci.
Conclusions:
- Altered NFκB nuclear dynamics, specifically sustained activity due to decreased IκBα, drive cellular senescence.
- This process involves NFκB-dependent epigenetic changes that enhance inflammatory gene expression, contributing to aging.
- Nuclear NFκB dynamics are critical in the progression of aging and age-related inflammation.
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