Senolytics safety in humans
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Senolytics Safety in Humans: Clinical Trial Evidence
Human Clinical Trials of Senolytics: Dasatinib and Quercetin
Several early-phase clinical trials have tested the safety of senolytic drugs, particularly the combination of dasatinib and quercetin (D+Q), in humans with age-related diseases. In a phase 1 trial involving patients with mild Alzheimer’s disease, D+Q was found to be well-tolerated over a 12-week period. All participants completed the study without early discontinuation, and no significant safety concerns were reported. Secondary measures, including cognitive and neuroimaging outcomes, did not show significant negative changes, further supporting a favorable safety profile in this small group .
Similarly, in a pilot study of patients with idiopathic pulmonary fibrosis (IPF), D+Q was administered intermittently over three weeks. The retention rate was 100%, and no participants discontinued due to adverse effects. Most side effects were mild to moderate, such as respiratory symptoms, skin irritation, and gastrointestinal discomfort. Only one serious adverse event was reported, suggesting that the regimen was generally safe and feasible for this population .
In another open-label phase 1 study in individuals with diabetic kidney disease, a short course of D+Q significantly reduced markers of senescent cells in tissues and blood. The treatment was well-tolerated, with no major safety issues reported Hickson2019Hickson2020.
Safety Concerns and Side Effects
Across these studies, the most common side effects of senolytic therapy were mild and included respiratory symptoms, skin irritation, and gastrointestinal discomfort . Serious adverse events were rare. Importantly, no early discontinuations due to safety concerns were reported in these trials Gonzales2023Justice2019Hickson2019+1 MORE.
However, some reviews and preclinical studies caution that senolytic drugs can have off-target effects. For example, navitoclax, another senolytic, is associated with hematological toxicity, and in vitro studies have shown that some senolytics may not always distinguish between senescent and healthy cells, raising concerns about potential unintended cell death Wang2021Zhu2017. This highlights the need for more refined and selective senolytic agents to improve safety Wang2021Zhu2017.
Natural Senolytics and Toxicity
Natural compounds with senolytic activity, such as fisetin and quercetin, are thought to have lower toxicity compared to some synthetic agents. Reviews suggest that these natural senolytics may be safer for human use, but more research is needed to fully understand their mechanisms and long-term safety Boccardi2021Zhu2017.
Ongoing Research and Caution
While early clinical trials indicate that senolytics like D+Q are generally safe and well-tolerated in humans, these studies are small and short-term. Larger, placebo-controlled trials are needed to confirm safety and efficacy. Experts recommend that senolytics should not be used outside of clinical trials until more robust evidence is available Boccardi2021Al-Naggar2020Kirkland2017+1 MORE.
Conclusion
Initial human studies suggest that senolytic drugs, particularly dasatinib and quercetin, are generally safe and well-tolerated in patients with age-related diseases, with mostly mild side effects and rare serious adverse events. However, concerns about off-target effects and the need for more selective agents remain. Larger and longer-term studies are required to fully establish the safety profile of senolytics in humans, and their use should currently be limited to clinical research settings Gonzales2023Justice2019Boccardi2021+7 MORE.
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