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Lipophilic Statins Eliminate Senescent Endothelial Cells by inducing Anoikis-Related Cell Death
Barbora Belakova1, Nicholas K Wedige1, Ezzat M Awad1,2
1Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
Abstract:
Pre-clinical studies from the recent past have indicated that senescent cells can negatively affect health and contribute to premature aging. Targeted eradication of these cells has been shown to improve the health of aged experimental animals, leading to a clinical interest in finding compounds that selectively eliminate senescent cells while sparing non-senescent ones. In our study, we identified a senolytic capacity of statins, which are lipid-lowering drugs prescribed to patients at high risk of cardiovascular events. Using two different models of senescence in human vascular endothelial cells (HUVECs), we found that statins preferentially eliminated senescent cells, while leaving non-senescent cells unharmed. We observed that the senolytic effect of statins could be negated with the co-administration of mevalonic acid and that statins induced cell detachment leading to anoikis-like apoptosis, as evidenced by real-time visualization of caspase-3/7 activation. Our findings suggest that statins possess a senolytic property, possibly also contributing to their described beneficial cardiovascular effects. Further studies are needed to explore the potential of short-term, high-dose statin treatment as a candidate senolytic therapy.
Insights
Statins, commonly used for lowering cholesterol, were found to selectively eliminate senescent cells, which contribute to aging. This senolytic property may enhance their cardiovascular benefits and suggests potential as an anti-aging therapy.
Area of Science:
- Cellular biology
- Gerontology
- Pharmacology
Background:
- Senescent cells negatively impact health and promote aging.
- Targeting senescent cells shows promise for improving health in aged individuals.
- There is a clinical need for compounds that selectively eliminate senescent cells.
Purpose of the Study:
- To investigate the senolytic capacity of statins.
- To determine if statins selectively eliminate senescent cells while sparing healthy cells.
- To explore the mechanism behind statin-induced senolysis.
Main Methods:
- Utilized two models of senescence in human vascular endothelial cells (HUVECs).
- Assessed the effect of statins on senescent and non-senescent cells.
- Investigated the role of mevalonic acid and caspase-3/7 activation in statin-induced cell death.
Main Results:
- Statins demonstrated a senolytic effect, preferentially eliminating senescent HUVECs.
- Non-senescent cells remained unharmed by statin treatment.
- The senolytic effect was reversed by mevalonic acid and involved anoikis-like apoptosis via caspase-3/7 activation.
Conclusions:
- Statins possess senolytic properties, potentially contributing to their cardiovascular benefits.
- Statins may represent a novel senolytic therapy, warranting further investigation.
- Short-term, high-dose statin treatment could be explored as a senolytic strategy.
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