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Updated: Nov 2, 2025
06:51
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
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Acid ceramidase promotes senescent cell survival
Rachel Munk1, Carlos Anerillas1, Martina Rossi1
1Laboratory of Genetics and Genomics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA.
Aging
|June 8, 2021
Summary
Acid ceramidase (ASAH1) promotes cellular senescence and protects senescent cells. Inhibiting ASAH1 sensitizes cells to senolytic drugs, making it a potential therapeutic target for age-related diseases.
Area of Science:
- Cellular and Molecular Biology
- Aging Research
- Biochemistry
Background:
- Cellular senescence is implicated in age-related diseases like atherosclerosis and neurodegeneration.
- Senescent cells exhibit distinct protein expression profiles compared to proliferating cells.
Purpose of the Study:
- To identify proteins differentially expressed in senescent human diploid fibroblasts.
- To investigate the role of acid ceramidase (ASAH1) in cellular senescence and response to senolytics.
Main Methods:
- Induction of senescence in human diploid fibroblasts via replicative exhaustion or ionizing radiation.
- Quantitative analysis of ASAH1 mRNA and protein levels.
- ASAH1 gene silencing using siRNA.
- Assessment of senescence markers (p16, p21, p53, β-galactosidase activity).
- Evaluation of senolytic drug efficacy (Dasatinib and Quercetin) after ASAH1 depletion.
Main Results:
- Acid ceramidase (ASAH1) was significantly elevated in senescent cells at both mRNA and protein levels.
- Increased ASAH1 protein stability contributed to its higher levels in senescence.
- ASAH1 silencing reduced senescence markers and sensitized cells to senolytics Dasatinib and Quercetin.
- ASAH1 promotes senescence, protects senescent cells, and confers resistance to senolytic treatments.
Conclusions:
- ASAH1 plays a crucial role in promoting and maintaining cellular senescence.
- ASAH1 is a potential therapeutic target for enhancing senolytic drug efficacy.
- Targeting ASAH1 may offer a novel strategy for eliminating senescent cells in age-related diseases.
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