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Destroying ‘Zombie’ Cells for Cardiovascular Health

A popular senolytic combination has shown effects in cells.

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Researchers have demonstrated that two senolytic drugs might improve how the heart repairs itself by destroying senescent cells [1]. These harmful cells are associated with many age-related diseases, including cardiovascular disease.

Zombie cells that refuse to die

As we age, our bodies accumulate senescent cells, often referred to as ‘zombie’ cells. These cells can impair the survival and repair capacity of nearby healthy cells.

Normally, when cells wear out or become too damaged to function, they destroy themselves with a self-destruct mechanism called apoptosis. Unfortunately, with aging, more cells avoid this process, and instead of dying, they become senescent cells.

Senescent cells enter cell cycle arrest, meaning they no longer divide and support their tissues. Their presence also means that healthy replacement cells cannot take their place in the tissue as part of the repair process.

Worst of all, these cells produce various chemical signals that increase chronic inflammation and are harmful to nearby healthy cells. This can lead to life-threatening conditions, such as cardiovascular disease and cancer, as well as other age-related illnesses.

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Two senolytic agents appear to destroy senescent cells

At King’s College London, Professor Georgina Ellison-Hughes and her team tested a class of drugs known as senolytics, which are designed to eliminate senescent cells.

Previous laboratory experiments have demonstrated that senolytics can positively impact medical conditions, such as cataracts, diabetes, Alzheimer’s, and heart failure. In addition, they have been shown to combat age-related muscle loss and prolong lifespan and healthspan in mouse models.

The researchers used two senolytic agents to destroy senescent cells: dasatinib and quercetin.

Dasatinib blocks cancer growth by stopping the interactions of particular proteins on cancer cells that encourage the cancer to grow. Recently, it was discovered that dasatinib seems to destroy senescent cells when combined with quercetin.

Quercetin is a flavonoid, a plant pigment that has been linked to potential health benefits, including anti-inflammatory and antioxidant properties. It is found in many fruits and vegetables, such as onions, apples, and various berries.

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In their experiment, the researchers grew senescent human heart cells and healthy human heart cells together in cell culture. These cells included cardiomyocytes, the cells that enable the heart to contract, and endothelial cells, which form the blood vessels.

The scientists demonstrated that when senescent cells are removed using senolytics, the survival and cell cycle activity of cardiomyocytes is improved. The capability of endothelial cells to form new blood vessels is significantly increased.

We still have more to learn about senescent cells

It appears that getting rid of senescent cells may help to restore the heart’s ability to repair itself. So far, clinical trials using senolytics have shown some promise, but the results have been a mixed bag. The authors suggest that doing more senolytic research in the lab would be beneficial.

Given recent results, it seems clear that our understanding of the nuances of senescent cell populations is far from complete. For example, Unity Biotech failed to achieve significant results in a clinical trial of senolytics.

That said, the idea of removing harmful senescent cells certainly has merit. We just need to work out which populations of these cells are the actual target. Fortunately, efforts are underway to chart and understand senescent cells and their different subpopulations. This will hopefully bring deeper understanding and refinement to the use of senolytics in future clinical trials.

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These results pave the way for further studies using senolytics to treat age-related heart conditions and the toxic effects of chemotherapy on the heart.

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Literature

[1] Ellison-Hughes, G. M., Sunderland, P., Alshammari, L., & Ambrose, E. (2022). Senolytics rejuvenate the reparative activity of human cardiomyocytes and endothelial cells. European Heart Journal, 43(Supplement_2), ehac544-2873.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.