How It Works: Senolytics work by targeting specific pathways that senescent cells rely on for survival. By disrupting these pathways, senolytics trigger the death of senescent cells while leaving healthy cells unaffected. Removing these cells reduces inflammation and improves tissue regeneration, which could slow the aging process.
Available Studies: Several animal studies have shown that senolytic drugs can extend lifespan and improve health markers in mice. One notable study published in Nature Medicine found that using senolytics in aged mice extended their lifespan by 36% and improved heart function, kidney health, and overall physical function.
Another study from the Mayo Clinic showed that treating mice with the senolytic drug combination of dasatinib and quercetin reduced the number of senescent cells in multiple tissues and improved age-related physical decline. The study noted: “Clearing senescent cells delayed multiple age-related disorders and extended healthspan.”
Availability and How to Use It: Senolytic drugs are still in the experimental phase, with human trials ongoing. The first human clinical trials, such as the UNITY Biotechnology trial, have shown promising results, but widespread availability is likely 5-10 years away. If successful, senolytic treatments could be administered in periodic doses to help maintain cellular health as we age.
How Senolytic Drugs Work
Senolytic drugs work by targeting the survival pathways that senescent cells rely on to avoid apoptosis (programmed cell death). Unlike healthy cells, senescent cells depend on specific pro-survival mechanisms to stay alive, despite being damaged or dysfunctional. Senolytic drugs disrupt these survival pathways, causing the senescent cells to self-destruct without affecting normal, healthy cells.
The removal of senescent cells helps reduce chronic, systemic inflammation (known as “inflammaging”) and can promote tissue repair and regeneration. This therapeutic approach has shown promise in preclinical animal models and early human trials for improving healthspan and delaying the onset of age-related conditions.
Examples of Senolytic Drugs and Supplements
Dasatinib (D)
Originally developed as a chemotherapy drug for treating leukemia, dasatinib has been found to have senolytic properties. It works by targeting senescent cells in certain tissues, such as the adipose (fat) tissue and the cardiovascular system.
Research: A 2018 study published in Nature Medicine found that dasatinib, when combined with quercetin (D+Q), significantly reduced senescent cell burden and improved physical function in aged mice. The same combination has shown promise in improving health markers in humans, particularly in conditions like idiopathic pulmonary fibrosis (IPF), where senescent cells accumulate in the lungs.
“Dasatinib, in combination with quercetin, effectively reduces the burden of senescent cells in aged tissues, improving overall health and function.”
Quercetin (Q)
Quercetin is a naturally occurring flavonoid found in fruits and vegetables like apples, onions, and berries. It has antioxidant and anti-inflammatory properties, and when used in combination with dasatinib, it has been shown to act as a senolytic, particularly in removing senescent endothelial cells (which line blood vessels).
Research: The same Nature Medicine study showed that dasatinib and quercetin together improved cardiovascular health and physical performance in older mice. Quercetin on its own also shows senolytic activity in certain cell types, including senescent endothelial and mesenchymal cells.
“Quercetin enhances the efficacy of senolytic treatment by selectively clearing senescent cells in various tissues, improving tissue health.”
Fisetin
Fisetin is another flavonoid, similar to quercetin, that is found in strawberries, apples, persimmons, and onions. It has shown potent senolytic effects in preclinical studies, and it is considered one of the more promising natural senolytics.
Research: A study published in EBioMedicine in 2018 demonstrated that fisetin effectively cleared senescent cells in mice, leading to an extended lifespan and improved healthspan. It was also found to reduce markers of senescence in human cell cultures, showing potential for therapeutic use in humans.
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Navitoclax (ABT-263)
Navitoclax is an experimental drug originally developed as a cancer therapy, particularly targeting BCL-2 family proteins that help cancer cells avoid apoptosis. It has been found to also target senescent cells, particularly in the hematopoietic (blood-forming) and immune systems.
Research: A study published in Nature Communications found that navitoclax eliminated senescent cells from tissues and improved regenerative capacity in aged mice. However, its use has been limited by side effects, such as thrombocytopenia (low platelet count), which can lead to bleeding risks.
“Navitoclax is a potent senolytic that effectively clears senescent cells in aged tissues, though its use may be limited by off-target effects.”
ABT-737
ABT-737 is another experimental drug that, like navitoclax, targets BCL-2 proteins and induces apoptosis in senescent cells. It has been studied primarily in preclinical models.
Research: Studies have shown that ABT-737 can selectively kill senescent cells in the liver and other tissues, improving tissue function in aged mice. Its senolytic activity has made it a candidate for further exploration, especially in the context of liver diseases related to aging.
“ABT-737 shows promise in targeting senescent cells in the liver, leading to improved liver function and reduced age-related decline.”
Piperlongumine
Piperlongumine is a natural compound derived from the long pepper plant (Piper longum). It has been shown to have senolytic properties, particularly by inducing oxidative stress in senescent cells, which makes them more vulnerable to apoptosis.
Research: In studies on human cell lines and mice, piperlongumine has been shown to selectively kill senescent cells and improve tissue health by reducing oxidative stress and inflammation.
“Piperlongumine’s ability to selectively induce oxidative stress in senescent cells makes it a promising senolytic candidate.”
Potential Benefits of Senolytic Drugs
Improved Healthspan: By clearing senescent cells, senolytics may help delay or prevent age-related diseases such as cardiovascular disease, diabetes, arthritis, and neurodegenerative conditions.
Tissue Regeneration: Removing senescent cells allows healthy cells to proliferate and repair tissues, potentially improving tissue function in aging individuals.
Reduced Inflammation: Senescent cells are major contributors to chronic inflammation, and senolytics can reduce inflammatory markers in the body, leading to better overall health.
Increased Physical Function: Animal studies show that senolytic drugs can improve muscle strength, endurance, and mobility in older animals.
Current State of Senolytic Research and Availability
Senolytic drugs are still in the experimental stage, with some compounds (like dasatinib and quercetin) being tested in human clinical trials. Early results are promising, particularly in conditions like idiopathic pulmonary fibrosis and osteoarthritis. However, widespread availability for general anti-aging purposes is likely several years away.
Senolytics like quercetin and fisetin, which are natural compounds, are already available as dietary supplements, but their long-term safety and efficacy in humans are still being studied. Synthetic senolytic drugs, such as navitoclax, will require more extensive clinical trials to ensure they are safe for widespread use in humans.
In conclusion, senolytic drugs offer a promising approach to slowing aging and treating age-related diseases by targeting the root cause—senescent cells. As research progresses, these therapies may become a cornerstone of anti-aging medicine, helping people live healthier, longer lives.
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