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Updated: Sep 21, 2025
Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Selective Growth Suppressive Effect of Pravastatin on Senescent Human Lung Fibroblasts
1Department of Analytical Biochemistry, School of Pharmacy, Iwate Medical University, Iwate, Japan; Department of Analytical Biochemistry, School of Pharmacy, Iwate Medical University, 1-1-1, Idaidori, Yahaba, Shiwa-gun, Iwate 0283694,
Abstract:
Various chemical reagents containing inhibitors of mitochondrial activity, antioxidants, nuclear factor-kappa B (NF-kB) inhibitor, mammalian target of rapamycin (mTOR) inhibitor and other clinical therapeutics were screened in order to identify those that selectively decrease the viability of senescent human lung fibroblasts. Cell viability was measured using the CCK-8 assay. The results showed that pravastatin, a drug for hyperlipidemia, decreased the viability of senescent cells but not non-senescent cells. The effect of pravastatin on senescent cells is thought to be due to the inhibition of cell proliferation, rather than cell death. The effect of pravastatin was further investigated using the glucose metabolism assay, which showed that glucose consumption was inhibited both in non-senescent and senescent cells and intracellular nicotinamide adenine dinucleotide (NAD) was decreased in senescent cells. Changes to the mRNA expression levels of senescence-associated genes in response to pravastatin treatment were quantified by real-time-qPCR. There were no significant changes in the relative mRNA expression levels of IL-1β, p16, p21, and p53 in pravastatin-treated non-senescent cells, whereas the expression of IL-1β and p16 were increased by pravastatin only in senescent cells. The results of this study suggest that pravastatin does not induce senolysis, but rather selectively inhibits the proliferation of senescent cells and that cellular senescence is enhanced by decreasing intracellular NAD and promoting IL-1β production.
Insights
Pravastatin selectively inhibits senescent lung fibroblast proliferation, not cell death. This hyperlipidemia drug decreases senescent cell viability by impacting glucose metabolism and increasing IL-1β production.
Area of Science:
- Cellular senescence research
- Aging and longevity studies
- Fibroblast biology
Background:
- Cellular senescence contributes to aging and age-related diseases.
- Identifying therapeutics that target senescent cells is crucial for anti-aging strategies.
- Senescent cells exhibit altered metabolic profiles and inflammatory signaling.
Purpose of the Study:
- To screen clinical therapeutics for selective reduction of senescent human lung fibroblast viability.
- To investigate the mechanism by which pravastatin affects senescent cells.
- To analyze the impact of pravastatin on cellular senescence markers and metabolism.
Main Methods:
- Screening of various chemical reagents and clinical therapeutics.
- Cell viability assessment using the CCK-8 assay.
- Glucose metabolism assays and real-time quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
Main Results:
- Pravastatin selectively decreased senescent cell viability without affecting non-senescent cells.
- Pravastatin inhibited glucose consumption in both cell types and decreased intracellular nicotinamide adenine dinucleotide (NAD) in senescent cells.
- Pravastatin treatment increased the expression of IL-1β and p16 in senescent cells, but not in non-senescent cells.
Conclusions:
- Pravastatin selectively inhibits senescent cell proliferation rather than inducing cell death (senolysis).
- Cellular senescence is promoted by decreased intracellular NAD and increased IL-1β production.
- Pravastatin shows potential as a therapeutic agent for targeting senescent cells.
