Forever Healthy Foundation Publishes a Risk-Benefit Analysis of Dasatinib and Quercetin as a Senolytic Therapy

The Forever Healthy Foundation publishes a series of conservative risk-benefit analyses of presently available interventions that might prove beneficial in addressing aspects of aging. These range widely in proven effectiveness, quality of animal evidence, and theoretical utility. Some do not in any way attack the known root causes of aging. Some are still pending any sort of rigorous human trial data. Some have plenty of human data that strongly indicates small, unreliable effects at best. It is nonetheless a useful exercise to make clear which are which. In a world in which the "anti-aging" industry propagates all sorts of nonsense to sell their snake-oil products, there is a comparative lack of good, unbiased analysis of approaches that might actually work to some degree, coupled with a responsible attitude towards uncertainty and risk.

The latest publication in the Forever Healthy series covers what is probably the best of the few presently available rejuvenation therapies, the use of dasatinib and quercetin in combination as a senolytic treatment. Senolytics selectively destroy senescent cells. These cells accumulate with age, and their presence actively maintains an inflammatory, dysfunctional state of metabolism, contributing meaningfully to the progression of degenerative aging and age-related disease. In animal models, senolytic therapies produce impressive results in turning back the manifestations of a wide range of age-related diseases. It is not hyperbole to say that this data is far, far better, more reliable, and more robust than the equivalent data for any other intervention targeting aging in old animals. Several small human trials have either been conducted and are underway for dasatinib and quercetin, and the published results to date are promising but not yet conclusive.

Risk-Benefit Analysis of Dasatinib + Quercetin as a Senolytic 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.

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.

Comments

While we are still musing and doing small human studies on the first generation of senolitics we already have the second generation like OISIN and pro-drugs which limit the off-site effects and allow for much higher dosage.

p.s.
When checking the yet to be published fisetin study, the dosage was 20mg/kg/day orally for 2 days in a row. For a 70kg weight that comes to close to 5 g a day, which i doubt can be easily absorbed, due its piss poor solubility and and bio-availability.

Posted by: cuberat at May 28th, 2020 3:50 PM

I took 200mg dasatinib + 2000mg quercetin about 10pm last evening. Woke up with severe chills and what felt like the worst flu I had ever had at 5am. It was so bad I wondered if I had Covid-19 and was having a bad reaction. I seriously thought it must be that as dasatinib had only caused mild reactions in human trials and was considered calling an ambulance to take myself to hospital, but decided to try and ride it out with some painkillers. Felt pretty shitty all day but feel back to normal now.

I don't know how all those people on trials only got mild side effects!? I definitely won't be repeating that until a weekend where I don't have to call in sick to work the next day.

Of course I purchased my dasatinib off alibaba, so maybe it wasn't actually dasatinib but was something else?

Posted by: european bob at May 28th, 2020 6:01 PM

@european bob
As far as I'm know 200 mg is considered high dose for D. And the regular users are fighting cancer, so your symptoms might be brushed away as there price you have to pay to fight the lymphoma. Or indeed, what you got is a bad batch.

And when doing such extreme experiments, you have avoid any activity that can cause wounds since the wild healing is slower and more scarring (fibrosis) when all senecent cells are killed. On top, d+q affect the blood clothing

But another question is how old are you to expect to have significant senescence cells burden? Do you have a condition you are trying to improve our you are simply adventurous?

For example, I have a whole bunch of small but manageable issues, and I tried Fisetin . I don't feel pressured enough to try dasatinib, as it is quite nasty with the off-site toxicity. Besides, before 50 , it seems the senecent cells burden is not that high, unless you had chemical or radiation poisoning. First generation Senolytics are quite blunt, and toxic while not cleaning all of the ScC. The second and third generations will be much more effective and safe. Also there are many tissue -specific senecent cells which will require different pathway targets. So probably we will need a cocktail of gen 2+3 Senolytics. At that point we might discover that there might be beneficial populations of ScC even in old age. It might even turn out that we have to kill only the ones that linger for too long and secrete too much pro inflammatory signals.

There are so many things we still don't know

Posted by: Cuberat at May 28th, 2020 9:03 PM

I was told by a brilliant researcher that if you take the dasatinib treatment prepare for possible extreme throwing up. He also advised having an epi pen at the ready in case of allergic reaction. Preparation as well as actual treatment is important.

Posted by: August33 at May 28th, 2020 10:03 PM

I am 43. I have chronic sinusitis unresponsive to topical glucocorticosteroid treatment. I cannot wait for 2nd and 3rd generation as the secondary constant infections that (might be caused) by the constant inflammation in my sinuses are causing me severe problems at work and I am facing financial ruin.

200mg of dasatinib is a high dose - if you were taking it every day like a cancer patient (they take 100mg every day). For a period of three days repeated over only 3 weeks taking 100mg or 200mg is not a high dose in my opinion.

Yeah the side effects sucked last time, but I will be taking dasatinib and quercetin again tonight as the side effects of continual unwellness suck a lot more.

I tried fisetin prior to this and it did not seem to have any effect. Perhaps fisetin does remove senescent cells in humans but steroid resistant upper airway disease is not driven by senescent cells?

Posted by: european bob at May 29th, 2020 3:09 AM

@european bob
Could you sinusitis be due to some chronic infection or allergy?
While not young you are far from being old. So your general senecent cross burden should be moderate, and your sinusitis might be caused by something else. Did you try dry fasting for 2-3days?

Posted by: Cuberat at May 29th, 2020 6:30 AM

I had blocked sinuses and fixed the problem by squirting warm salty water up my nose twice a day. Could work for sinusitis as well, nothing to lose.

Posted by: John S at May 29th, 2020 8:20 AM

My 73 year old father tried the D + Q combination almost two years ago, the first dose at 50 mg D he had almost no side effects and was willing to go to a higher dose so a week later he tried 100 mg D this time he felt absolutely miserable and decided never to do it again though a couple weeks later he did mention that his exercise endurance went up a bit and that his asthma symptoms decreased.

Posted by: Corbin at May 29th, 2020 9:48 AM

Took the second dose of 200mg dastinib + 2000mg quercetin yesterday.

Did not suffer the same flu like chills and unwellness feeling this time, although lungs do feel a bit sore today.

Sinuses are still sore and (probably) smoldering with inflammation. Will take the third dose this afternoon.

Posted by: european bob at May 30th, 2020 8:06 AM

Something to try for the sinus problem and may work for general congestion:

I have mixed a few drops of oregano oil with coconut oil. The oregano oil is a pretty effective anti-fungal and anti-bacterial agent. It is painful when used in a high concentration though. Use a swab to get the oil mix up in the nostril so that the vapors from the oregano oil can work through all of the sinus passages and also into the lung. Certainly unlikely to cause harm.

Posted by: aaCharley at May 31st, 2020 2:05 PM

Having flu-like symptoms is a common side effect, I never had that. A did a 50 mg dose as a test with no reaction and then did the 200/2000 dose and I had a slight headache the next day (healthy 58yr). Repeated again 7 months later with another slight headache. A dramatic increase in stamina, recovery, and balance the first time with a far less noticeable effect the second. It works especially well with stamina and balance. Do a balance check before your dose to see for yourself. I plan on doing a 3-day dose in the near future. No significant changes in pre-post lab work. Perhaps the higher your senescent cell burden the worse your side effects.

Posted by: Larry at June 1st, 2020 3:09 PM

Starting with a small dose is the best thing to do. In some it causes blood pressure to rise dramatically so monitor your blood pressure and perhaps take Ramipril 5mg if it goes very high. Am stuck in the UK because of lockdown so have been trying to get the NHS to start running trials of D & Q. Dasatinib has lost patent protection in Europe so the NHS (NICE) are targeting a price of nine pounds ($11) per treatment.

Posted by: Tj Green at June 1st, 2020 6:45 PM

It depends on what you would consider "snake oil" and as for the article you linked to, you go with the armchair Psychological analysis of people which is just lazy.

Posted by: J at June 3rd, 2020 12:18 AM

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