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A small-scale human trial by Mayo Clinic researchers has shown for the first time that harmful senescent cells that accumulate with age can be removed from the body by senolytic drugs. This has been demonstrated many times already in mice, but this is the first confirmation that these drugs remove senescent cells in the same way in people.

What are senescent cells?

As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.

Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.

By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging [1, 2].

Senescent cells only make up a small number of total cells in the body, but they secrete proinflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging [3] and cancer [4]; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.

Confirmation it works in humans, not just mice

The human trial, which involved a small number of participants who had diabetes-related kidney disease, investigated if the combination of cancer drug dasatinib and the widely available supplement quercetin was able to remove senescent cells in people [5]. The results were confirmed by analyzing factors present in the blood as well as changes to the presence of senescent cells in both skin and fat tissue.

The participants were given the combination of dasatinib and quercetin for just three days, but the effects were seen for at least 11 days following the initial dose. Based on the blood biomarkers the researchers used, as well as the tissue samples examined, the data suggests that this combination of drugs was able to remove a significant amount of senescent cells.

Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans.

Conclusion

While these initial results are promising, we should also bear in mind that this trial only involved 9 individuals (2 females and 7 males), and a further large-scale study is needed with a wider range of biomarkers used to justify the therapeutic use of senolytics in people.

That said, these results build on the previous study that the same team did, which focused on the treatment of IPF using the same drug combination, and the data is certainly promising and worthy of further investigation.

If you would like to dive a bit deeper into the data from the study, Dr. Oliver Medvedik recently covered the published paper in the September edition of the Journal Club.

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Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] van Deursen, J. M. (2014). The role of senescent cells in ageing. Nature, 509(7501), 439-446.

[3] Freund, A., Orjalo, A. V., Desprez, P. Y., & Campisi, J. (2010). Inflammatory networks during cellular senescence: causes and consequences. Trends in molecular medicine, 16(5), 238-246.

[4] Coppé, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annual review of pathology, 5, 99.

[5] Hickson, L. J., Prata, L. G. L., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., … & Kellogg, T. A. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine.

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 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. 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. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
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