Risk-Benefit Analysis of Dasatinib + Quercetin as a Senolytic Therapy
The Forever Healthy Foundation announces the public launch of the Risk-Benefit Analysis of Dasatinib + Quercetin as a Senolytic Therapy, a structured review of the published evidence. It is the fifth publication of Forever Healthy’s “Rejuvenation Now” initiative following the “Risk & Benefit Analysis of Vascular Rejuvenation using EDTA”.
Forever Healthy’s “Rejuvenation Now” initiative seeks to continuously identify potential rejuvenation therapies and systematically evaluates them on risks, benefits, and therapeutic protocols to create transparency regarding the current state of said therapies.
Dasatinib + Quercetin – a powerful rejuvenation therapy?
When a cell reaches the end of its life or becomes damaged beyond repair it normally either kills itself or signals the immune system to remove it. Unfortunately, every so often this mechanism fails. The cell stays around indefinitely and starts poisoning its environment. Over time, more and more of these harmful, death resistant, senescent cells accumulate. Senescent cells are thought to be one of the main drivers of aging and age-related diseases.
Senolytics are drugs that selectively remove senescent cells by disabling the mechanisms that allow them to survive. Dasatinib (D), a well-established medication used in the treatment of cancer and quercetin (Q), a flavonoid common in plants were among the first senolytics to be discovered. As they have been shown to affect different types of senescent cells, they are often employed in combination.
Studies in rodents have shown that clearing senescent cells can prevent, delay, or alleviate multiple age-related diseases and extend the healthy lifespan by up to 35%. Based on the promising results in animal testing, it is supposed that intermittent dosing of D+Q also leads to the elimination of senescent cells in humans with the accompanying health and rejuvenation benefits.
As the first clinical trials in humans have been completed and interest in the practical application of D+Q is increasing, Forever Healthy seeks to assess the risks, benefits, and therapeutic protocols of using D+Q as a senolytic therapy.
Methods & Results
For this risk and benefit analysis, the team at Forever Healthy screened more than 3300 scientific papers and included over 150 clinical and pre-clinical studies in its analysis.
Currently, there are only results from 3 trials in humans in which D+Q was evaluated as a senolytic therapy. The majority of human studies used D or Q in cancer therapy and provided information on side effects and safety.
The benefits shown in animals were significant and were observed in many organ systems. However, several of the benefits only occurred in diseased animals (i.e. diabetic mice), while the healthy control group did not benefit from the treatment.
The benefits reported in human studies are mainly focussed on senescent cell markers. So far, these markers are only hypothesized to translate to clinically meaningful effects. Few benefits had direct clinical relevance, and those were not really convincing. Additionally, 2 out of the 3 clinical studies were in patients with pre-existing disease so there is very limited information on the effect in healthy individuals.
The potential risks of D are extensive and well-known through its use in the treatment of cancer. While the clinical trials that used D+Q as a senolytic therapy reported only mild to moderate adverse events, it is of note that the low number of participants in these studies might not deliver a representative result.
Furthermore, the human studies all used different treatment protocols and there is no consensus on the measurement of efficacy in clinical practice.
Therefore, until there are more studies showing benefits in humans, a clearer picture of the senolytic-use specific risk profile, and a consensus on a treatment protocol, it seems prudent to avoid the use of D+Q as a senolytic therapy.
More details, including an in-depth analysis of all risks & benefits, can be found here.
About Forever Healthy
Forever Healthy is Michael Greve’s humanitarian initiative with the mission of enabling people to vastly extend their healthy lifespan.
Through its “Maximizing Health” and “Rejuvenation Now” initiatives Forever Healthy reviews the latest medical knowledge, creates actionable guides to maximize health and well-being and evaluates currently available rejuvenation therapies.
The foundation’s “Health & Longevity Strategy” combines the results of “Maximizing Health” and “Rejuvenation Now” with the latest knowledge from selected experts to create a step-by-step guide on how to maximize our health, well-being, and longevity right now.
Forever Healthy’s annual Undoing Aging conference brings together leading scientists and startups from around the globe to accelerate the development of human rejuvenation therapies.
For more information, please visit: forever-healthy.org
Dr. Isabelle Schiffer
Forever Healthy Foundation gGmbH
Amalienbadstr. 41, 76227 Karlsruhe
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