A Non-Invasive Biomarker to Measure the Effectiveness of Senolytic Drugs

Researchers here note the discovery of a non-invasive biomarker that can measure the pace of destruction of senescent cells. This could be used to more rapidly quantify the effectiveness of potential senolytic treatments, those capable of destroying senescent cells, thus speeding up development of the next generation of senolytic drugs. Readily available small molecule treatments (such as the dasatinib and quercetin combination) can destroy a fraction of senescent cells throughout the body, and in doing so produce rejuvenation in animal studies. Alongside bringing those first treatments to the clinic, the next goal in line is to achieve a much greater level of clearance. A great deal of work lies ahead in that optimization process.

Researchers have discovered and are developing a novel, non-invasive biomarker test that can be used to measure and track performance of senolytics: a class of drugs that selectively eliminate senescent cells. "The list of age-related diseases definitively linked to cellular senescence keeps growing, as does the number of biotech companies racing to develop drugs to eliminate senescent cells. While the field has never been more promising, the lack of a simple biomarker to measure and track efficacy of these treatments has been a hindrance to progress. We are excited to bring this new biomarker to the field and look forward to it being used in the clinic."

This work, performed in human cell culture and mice, shows that senescent cells synthesize a large array of oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids. "Lipid components of the senescence-associated secretory phenotype (SASP) have been vastly understudied. The biosynthesis of these signaling lipids promotes segments of the SASP and reinforces the permanent growth arrest of senescent cells." Oxylipins are implicated in many inflammatory conditions including cardiovascular disease and pain response. Many commonly used drugs, such as aspirin and ibuprofen, act by preventing oxylipin synthesis.

Senescent cells change their fatty acid metabolism and they do it in such a way that free polyunsaturated fatty acids accumulate inside the arrested cells where they are used to manufacture oxylipins. Researchers identified one of these fatty acids, 15-deoxy-delta-12,14-prostaglandin J2 (dihomo-15d-PGJ2), as unique to senescent cells; it accumulates inside senescent cells and is released when the cells die. In this study, mice were given chemotherapy which induces widespread senescence, followed by a senolytic drug. The biomarker was only detected in the blood and urine of mice treated with both chemotherapy and the senolytic, but not with either on its own, confirming specificity for senolysis.

Link: https://www.buckinstitute.org/news/the-first-non-invasive-biomarker-to-track-and-verify-efficacy-of-senolytic-drugs/


Very good news! I hope they can validate it in human trials soon.

Posted by: Antonio at April 8th, 2021 6:43 AM

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