The Scripps Research Institute – Dasatinib and Quercetin

Summary

The Scripps Research Institute, in partnership with Mayo Clinic, has discovered a combination of drugs that destroy harmful senescent cells, greatly increasing healthspan in a mouse model. These drugs, called senolytics, offer a novel method of treating age-related diseases.

One of these compounds is Quercetin, a natural antihistamine and anti-inflammatory agent that is often sold as a supplement. The researchers reported that Quercetin was effective against senescent human endothelial cells. The other compound is Dasatinib, a drug that is used in the treatment of bone cancer. It was found to be effective in destroying senescent fat cell progenitors.

Because these two compounds have different strengths, the researchers chose to test the two in combination. This combination strengthened mice that were weakened by radiotherapy treatment, extended the health of mice with accelerated aging, and improved the cardiovascular function of old mice.

While other organizations have since developed other senolytic drugs, this use of Dasatinib and Quercetin is considered to be the first attempt in the world of directly removing senescent cells.

A phase 1 human study was successfully concluded and the data published in early 2019 where Dasatinib and Quercetin were used to treat Idiopathic Pulmonary Fibrosis [3].

References:

[1] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.

[2] Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., … & Zhu, Y. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging cell, 15(5), 973-977.

[3] Nambiar, A., Justice, J., Pascual, R., Tchkonia, T., Lebrasseur, N., Kirkland, J., … & Kritchevsky, S. (2018). Targeting pro-inflammatory cells in idiopathic pulmonary fibrosis: an open-label pilot study of dasatinib and quercitin. Chest, 154(4), 395A-396A.

Website: https://www.scripps.edu/news/press/2015/20150309agingcell.html