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Updated: May 30, 2025
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Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
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Carboxyl Terminal Modulator Protein Induces Cell Senescence and Is Upregulated With Aging by Zic2 in Rats
Weiran Shan1, Jun Li1, Zachary Philpot1,2
1Department of Anesthesiology, University of Virginia, Charlottesville, Virginia, USA.
Journal of Cellular Physiology
|January 31, 2025
Summary
Carboxyl terminal modulator protein (CTMP) increases with aging and induces cell senescence. Zinc finger protein Zic2 suppresses CTMP, and its age-related decrease contributes to elevated CTMP levels in the brain.
Area of Science:
- Neuroscience
- Cell Biology
- Aging Research
Background:
- Carboxyl terminal modulator protein (CTMP) is implicated in various physiological and pathological processes.
- Previous research indicated CTMP increases with age and affects brain ischemic tolerance.
- The regulation of CTMP expression during aging and its impact on cellular senescence remain unclear.
Purpose of the Study:
- To investigate the regulatory mechanisms of CTMP expression with aging.
- To determine the effect of altered CTMP levels on cell senescence.
- To elucidate the role of Zinc finger protein Zic2 (Zic2) in CTMP regulation.
Main Methods:
- Stable CTMP overexpression in cells to assess senescence biomarkers.
- Western blot and immunostaining in Fischer 344 male rat brains to detect CTMP and Zic2.
- Promoter activity assays to examine Zic2's regulation of CTMP expression.
Main Results:
- CTMP overexpression enhanced senescence markers (e.g., β-galactosidase staining) and reduced cell proliferation.
- Zic2 expression decreased with aging in rat brains, where both Zic2 and CTMP are neuronally expressed.
- Zic2 was found to bind CTMP gene promoter fragments and inhibit its activity, reducing CTMP levels when overexpressed.
Conclusions:
- CTMP induces cellular senescence.
- Zic2 acts as a suppressor of CTMP expression.
- The age-related decline in Zic2 contributes to increased CTMP levels during aging.
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