#21

@Todd Have you considered temporarily stopping either the Rapamycin or the senolytics to figure out which is helping you?

#22

I"m no medical doctor and have no qualification to give medical advice, but all of my research says Rapamycin and Senolytics treatments have no relevance for someone thatā€™s only 28 years old. Geometrically increasing senescent cell burden generally doesnā€™t begin until crossing the age 40 barrier, and rarely compounds into a noticeable problem with physical symptom manifestations until mid-50s to mid-60s (based on my friend group of aging athletes). It takes years for this stuff to develop in a normally aging population. Age 28 doesnā€™t apply. My two cents worth.

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#23

No, I have no intention of stopping as long as all of my markers are moving in the right direction. Why fix it if itā€™s working?

I was in a full-blown health crisis at age 60, and I feel better today at age 63 than I did at age 40.

Stopping one (or both) of the treatments after the positive change isnā€™t likely to tell me anything useful. I took those meds for a reason, and the results matched expectations.

Iā€™m clear (from extensive research) why Iā€™m using these specific treatments and how they relate to the aging process, and the past 3 years show that theyā€™re playing well with my body.

The only motivation for change would be if I learn something new that points toward something better (which I fully expect to occur every year with all the research in this field), or if I see my markers move adversely.

Until then, Iā€™m not going to tinker with something thatā€™s working.

Hopefully that makes senseā€¦

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#24

I think your post makes logical sense, but you are making some assumptions. Are Rapamycin, Dasatinib and Quercitin completely safe medications, especially when combined? Are they safe when used chronically?
Should you take 3 medications when 1 might have the same benefit?
Iā€™m happy for you that you have had success. I see one of the purposes of this website is to question each other since there is so much unknown about what we are doing. I also go by the oath of ā€œfirst, do no harmā€.

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#25

The problem is it takes too long to test the individual variables.

Though I personally would not take D+Q except intermittently, though many people are taking low doses of dasatinib for extended periods. I certainly wouldnā€™t recommend it for any extended time if you are younger than 60.

Many people do take dasatinib long-term, especially those with chronic myeloid leukemia.

There is some evidence that dasatinib might prevent certain forms of cancer.

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#26

I understand what youā€™re saying. And I have no problem with your questions.

I just see it differently.

ā€œFirst, do no harmā€ is replaced with ā€œaging does harm.ā€ Inaction (and action) both have consequences.

I agree with @desertshores on both points - the testing suggestion youā€™re offering isnā€™t practical, and senolytics should be taken intermittently. I consider my ā€œonce every two monthā€ an appropriate intermittent protocol given the research. Fully agreed on both counts.

Yes, Iā€™m making assumptions. We both are. Theyā€™re just different.

Yes, thereā€™s uncertainty in every decision Iā€™m making. But Iā€™ve done the research and Iā€™m comfortable with the decisionsā€¦ for now. Iā€™m not winging it. All decisions are based on known research and followed up with biomarker testing. Each medication has different effects. The interrelationship are complicated. Fully agreed.

So yes, thereā€™s uncertainty and risk. But that risk is being managed to the best of my ability. ā€œFirst do no harmā€ is being replaced with a minimalist approach of intelligent risk-managed decisions. My stack is tiny compared to many people because I believe far more is unknown about human biology than known. I say ā€œnoā€ to new ideas/supplements far more often than ā€œyesā€ to respect the inherent systemic elegance and beauty of human biology.

But aging is inherently risky. And enough is known to take intelligent, risk-managed action to improve outcomes. First do no harm no longer makes sense as offering the best risk/reward outcome.

I fully expect to change this protocol going forward, but not in the way youā€™re suggesting. I fully expect game-changing discoveries in the field of senolytics and rapalogs that will be vastly superior to what Iā€™m doing now. Iā€™m guessing my current treatment protocol will look laughably crude 20 years from now, but 20 years is too late. Time is of the essence.

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#27

That is certainly my motto at 83 :sweat_smile:

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#28

Seriously? Stop D&Q for a few months. See how you feel.

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#29

Iā€™m guessing from your statement that youā€™re not understanding the role of senescent cell population growth in aging and how senolytics and senomorphics interact to affect the aging process.

The net compound growth of your senescent cell population only becomes meaningful when measured over many years (a couple decades by age 63, in my case), or 4 decades for @desertshores), and it only becomes symptomatic to how you feel when that burden exceeds certain thresholds of concentration in specific tissues.

You can think of it like a compound return equation in wealth building. When you start at $100, you hardly notice the first few doubles in your wealth (same with senscent cells after age 40). The accumulation remains relatively meaningless. But when you hit 2 million dollars (think age 55-65) and then double again, that sudden accumulation has life-changing implications. The same is true with the senescent burden in your tissues as you compound them during aging.

The chance that Iā€™ll feel any different after a few months of stopping D&Q is unlikely, not to mention that that subjective changed ā€œfeelingā€ could be due to any number of confounding life factors that have nothing to do with cessation of D+Q. Itā€™s simply not a valid test.

Additionally, any subjective change in experience of life with and without D+Q already occurs between every dose since I only take it once every two months. That means my system already spends the vast bulk of itā€™s time without any D+Q. Taking an extended break would change only one thing - the compound growth of the underlying senescent cell population.

Finally, a few months of change would be similarly meaningless because the existing dosing regimen would mean I would only miss a handful (or less) samples. Thatā€™s also not going to be meaningful in this compound growth equation given my current position in that equation.

My suggestion is to study senolytics with a special emphasis on the work by Dr. James Kirkland. Heā€™s a leading researcher in this field providing unusual insights on this topic.

Hope that helps!

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#30

So, can you then stop the Rapamycin?
Iā€™ll have to look into senolytics again, but I just havenā€™t seen much that convinces me that they offer much beyond what Rapa is doing.

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#31

LOL! If you want to stop Rapamycin then thatā€™s up to you.

It doesnā€™t make any sense for you to ask another person to test your theories on their health.

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#32

Weā€™ll get better data from you than from a mouse.

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#33

I think when you hit 55-60 yo, it is appropriate to start taking D+Q if you want. Probably on an annual or every 6 month protocol.

I expect Rapamycin and Taurine to do the heavy lifting on reducing senescent cells burden though.

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#34
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#35

It always strikes a wrong chord with me when the title of something is grammatically incorrect. It should be ā€˜Fewerā€™ instead of ā€˜Lessā€™.

However, this is from Michael Lustgarten, so he gets a pass.

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#36

Many ongoing trials of the *tinib family with results expected this year and next year: Parkinson's disease - #341 by adssx

@John_Hemming what are your thoughts on dasatinib and other drugs of this class?

My main concern is the adverse events:

Common adverse effects include low white blood cells, low blood platelets, anemia, swelling, rash, and diarrhea. Severe adverse effects may include bleeding, pulmonary edema, heart failure, and prolonged QT syndrome.

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#37

I have not spent a lot of time looking at dasatinib. It strikes me, however, that it is not targeting the generic issue of gene expression and/or mitochondrial efficiency. I tend to be interested in things that improve the mitochondria or gene expression more generally.

When it comes to senescent cells
a) I think a lot of them are stem cells that have got stuck in the process of differentiation because of low power levels.
b) My objective would be (is) to make them function rather than kill them.

I think there are dangers potentially in some circumstances (like in the walls of arteries) with just killing off senescent cells. Also this will act to deplete stem cell availability.

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