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Multi Pronged Senolytic Attack (Dasatinib + Azithromycin + More).... I am ready

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#31 bobolander

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Posted 04 October 2019 - 07:21 PM

I agree that combining senolytics "willy nilly" as someone said, is potentially dangerous, but at 84 I feel the risk reward ratio has shifted.  I take many supplements and a weekly dose of 2.5mg Rapamycin.  I started taking 50mg Desatanib and 1.5gm Quercetin monthly January 2016.  Starting January 2018 I switched to a quarterly regimen of 100mg Desatanib, 1gm Quercetin, 500mg Azithromycin and 1gm of Fisetin.  I have suffered no significant health issues or side effects that I can attribute to my supplement regimen and am still healthy enough to play weekly tennis.  My Spring 2019 Zymo DNAm blood test was 75 and the urine age 71.  


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#32 Mind

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Posted 05 October 2019 - 01:58 PM

For the "Vitality in Aging" study, the "interventions" part is going to use Dasatinib, Quercetin, and Fisetin. I am guessing they chose this combination because they have well-known and minimal negative side effects.



#33 OP2040

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Posted 01 February 2020 - 02:42 PM

For the "Vitality in Aging" study, the "interventions" part is going to use Dasatinib, Quercetin, and Fisetin. I am guessing they chose this combination because they have well-known and minimal negative side effects.

 

This is the combination I'm using as well as Curcumin, and I'm starting my little mini-trial today.  I am a bit skeptical as well about combining senolytics.  It's very clear from animal studies that combining nutrient-sensing targets (mTOR/IIS/Sirtuin/AMPK) can have a positive cumulative effect.  In contrast, I haven't read anything to that effect for senolytics, aside from the D+Q combo.

 

Anyway, I'll offer a play-by-play here over the next couple days.  Started this morning with the following:

C (with bioperine) - 2250mg

F - 800mg

Q - 500mg

D - 25mg

 

Had milk in my coffee and a reasonable sized swig of olive oil for fat.  As for why I'm only taking 25mg D for now, it's basically a dose escalation since I've never had it before. And quite frankly, it makes me extremely nervous.  I'll get close to 100mg by end of day if all goes well.

 

Other factors, I stopped all other supplements for the previous 4 days. Stay tuned....


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#34 OP2040

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Posted 01 February 2020 - 08:43 PM

End of day update:

 

I've finished my entire protocol for today, including the 100mg of Dasatinib.  I have one overwhelming and undeniable thing to report.  Ive been ravenously hungry all day since my first dose, and it has generally increased with further dosing.  I'm eating the exact same way that I always do but I feel like I haven't been this hungry in years.  I have to say I used to foolishly take pride in my lack of hunger.  I could skip breakfast and even lunch easily and not be all that hungry.  Somewhere along the line I realized that not being hungry is not a good thing and it's definitely age-related.  I'm actually really enjoying this feeling of being hungry. Has anyone else had this experience with Dasatinib?  It has to be that because the other things I've taken before.

 

Everything aside from the hunger is going to be subjective but I'll report a couple other things.  My mood seems to be noticeably lifted.  As for negative side effects, I have no idea what I was so worried about.  I feel nothing negative whatsoever, not even the flu-like symptoms many report.   But the hunger, oh man the hunger, can't wait for dinner.

 

Sorry I'm the typical unscientific poster with no lab tests, etc.  But I am getting my general checkup in a month or two, so that is pretty good timing. I'll update some more tomorrow.


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#35 OP2040

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Posted 02 February 2020 - 12:55 PM

Day 2:

OMG, why didn't you guys tell me!  Last night after satisfying my ravishing hunger, I started to feel the famous flu-like effects everyone talks about.  Mild but persistent nausea, mild runny nose, mild cough, just generally feeling under the weather.  I understand what others were saying now.  Basically, unlike other interventions, there is absolutely no questioning that Dasatinib is doing "something". 

 

I've taken my Fisetin and Curcumin this morning.  I'm about to take my D+Q but I may take the dose down to a total of 80mg on day 2.  Thank god I can work from home tomorrow.

 

One interesting parameter to report.  I took my temperature fully expecting to have a fever, but to my surprise it was 96.6.  I've taken my temp over the years and it's always been in the normal range, not low.  Interesting, not sure what it means.


Edited by OP2040, 02 February 2020 - 12:59 PM.

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#36 OP2040

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Posted 05 February 2020 - 06:46 PM

Day 5: Post-Treatment update

 

Well, I'm a humble man and I'm going to admit right here that I almost did myself in with this via sheer stupidity and laziness.  In the interests of science, this should be documented somewhere.  I'll get to all my observations, but let me just get right to the main point.  I took the C+F+Q as described above.  But i accidentally took a massive dose of the D, many times more than what anyone has reported here, mainly due to being way to casual in my procedure.  I basically used a scale to measure out the dose and so you can do the calculation of my stupidity yourself by dropping a zero.  

 

Anyway, on to the implications of this unique, life-threatening experiment.  On day 2, I realized my mistake and stopped taking D immediately.  This still means I got 2-3 huge doses thankfully spread out over the course of one 24 hour period.  Because of the D half-life, this can be thought of as an effective dose for elimination of senescent cells.  As described above, on day 2, I had the paradoxical flu-like symptoms alongside low body temp and muddled through.

 

On day 3 I had the flu-like symptoms less consistently and by the end of the day they were mostly gone.  The mild nausea was also less consistent.  However, by the end of day, after a large meal, I felt some pain in the liver area, specifically what people would describe as gall bladder area.  I also had mild constipation that only stopped today on day 5.  While I was technically defecating, it was limited and quite different from my normal once-a-day, post-coffee perfection.  Other than this there was no other typical signs of liver damage.  i did hastily down a NAC, though if there was liver damage, the timing may have been a bit late.  Anyway, this pain in the gall area had me almost to urgent care when it was acute and at it's worst.  

 

On day 4, thankfully I woke to no pain or discomfort in that area.  I did have a very raised pulse many times during this day, whereas my normal resting pulse is almost always 60 and sometimes below.  I was rather disappointed that all my usual age-related discomforts were back.

 

Day 4 evening up until now.  This is where it is starting to get interesting.  Some of my long-standing, stubborn, age-related discomforts have shown some signs of relief.  I'm not overly excited as we have all been disappointed before with transient effects.  But I'll report back in a couple days again on all of that.

 

I noticed in the human study they did with D+Q, they took the follow-up test for senescent cell burden on day 14.  Does anyone know why they would do this.  My previous assumption was that this is a fairly quick process.  Is there any evidence that it takes upward of a couple weeks for senescent cells to flush out of the body?  

 

Onward and Upward!


Edited by OP2040, 05 February 2020 - 06:48 PM.

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#37 OP2040

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Posted 07 February 2020 - 02:45 PM

Day 7:

 

This will be my last update unless something dramatic changes.  Obviously I am still here, so I effectively conducted a toxicology study for humans based on maybe 10X the normal dose of Dasatinib,  YW, slow-moving scientific community! 

 

Anyway,  I am happy to report that some of the beneficial effects I noticed are sticking around.  I am walking a fine line here regarding whether I'm over or under-playing the effects.  The concern about exaggerating at this point is limited to whether the effects will stick around.  We all know that there are times when we experience remission of the symptoms of aging for brief periods only for it to return with a vengeance.  So without detailing my personal health data too much, let me elaborate on myself a bit and my experiences.  I'm 45 and 1/2, so not old and not young.  Although there is debate, I am personally convinced that serious aging starts around 40 for humans.  That has been my experience and when I see a counter-example it is often due to people being very diligent or lucky.  You can actually see this quite clearly in sports, where 40 is often considered old and noncompetitive, with the rare exceptions usually encompassing the least physical sports and positions. 

 

Anyway, onto me.  After age 40 my problems became the inflammatory/metabolic trajectory.  And it is in those measures I am convinced this intervention has helped.  I'm not going to tally everything because it is all the usual subjective stuff.  But some subjective observations are more solid than others.  I know when I feel stiffness in my legs every day from a sit down job for example.  And I sure as hell notice when that stiffness disappears overnight!  That's an example of the change in trajectory from this intervention.  

 

I've discovered that a lot of people, including myself, just don't like to monitor every aspect of their health with biometrics.  I think it actually makes a lot of logical sense.  There are no current cures for aging related conditions.  So constantly monitoring your HRV for one example, is an exercise in hopelessness and depression.  Sure, you will have victories, but they will by definition be short term.  This is why I believe we have such a hard time getting people to do actual, useful scientific observations.  I actually did my whole genome sequence when it was relatively new, and a lot of people offer that as an example.  They say "why would I want to know, when I can't change it".   

 

The good news is that all of this will change.  Senescent cells are a good example.  I'm dying to find out what my level of senescent cells are.  And this is ONLY because I'm convinced that it's now in my control to powerfully change that number for long periods of time.  bah tl;dr


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#38 HBRU

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Posted 01 March 2020 - 08:59 AM

IP6 may help both in senolitic protocols and virus infections ??

https://www.livescie...accomplice.html
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#39 ortcloud

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Posted 27 May 2020 - 09:25 PM


Anyway,  I am happy to report that some of the beneficial effects I noticed are sticking around.

 

Any updates? Have you run any bloodwork?



#40 OP2040

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Posted 27 May 2020 - 11:21 PM

I did have my general checkup a few weeks after this intervention. I had a metabolic panel in which my parameters were all within range. But I guess that doesn’t say much since they’ve never been out of range so far.

All the other things I mentioned are about the same and nothing exciting.

I also got a telomere test after as well, but not before. Afraid to look at it to be honest lol.
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#41 aribadabar

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Posted 30 May 2020 - 10:00 PM

I did have my general checkup a few weeks after this intervention. I had a metabolic panel in which my parameters were all within range. But I guess that doesn’t say much since they’ve never been out of range so far.

All the other things I mentioned are about the same and nothing exciting.

I also got a telomere test after as well, but not before. Afraid to look at it to be honest lol.

 

Fear not - we can give you ideas both if they are too long or too short  :)


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#42 ortcloud

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Posted 08 December 2020 - 10:24 PM

Day 5: Post-Treatment update

 

 But i accidentally took a massive dose of the D, many times more than what anyone has reported here, mainly due to being way to casual in my procedure. 

 

I basically used a scale to measure out the dose and so you can do the calculation of my stupidity yourself by dropping a zero.  

 

 

So how much dasatanib did you actually take? 250mg?



#43 OP2040

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Posted 09 December 2020 - 02:26 PM

So how much dasatanib did you actually take? 250mg?

 

My best guess it more like1000mg over the course of an entire day/night.   I'm still alive and not much has changed.  As stated, my panels came out fine, in particular liver was fine as always. 


Edited by OP2040, 09 December 2020 - 02:27 PM.

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#44 ortcloud

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Posted 12 December 2020 - 11:03 PM

 

Once in it you need to clear senescent cells out far more frequently. In my experience, once every 2-4 weeks when you reach your middle sixties. And once you are past that crisis period -- if you've managed to replace your senescent cells -- then it ought to be smooth sailing for decades more.

 

@Turnbuckle, I have been thinking alot about your post that there is a period of time and somewhat of an end point to having to do senolytics.

 

Since senolytics are fairly new for most people I dont think anyone has actually made it through like you and most probably assume you have to do them for the rest of your life, I know I did.

 

I am very curious how long it took you to get through this period of clearing out senescent cells?



#45 Rocket

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Posted 14 December 2020 - 01:54 AM

If one senolytic therapy is enough to clear out the majority of your senescent cells, then you only need it once. Then maybe do the treatment a few years later.

At this point in senolytic research, it would be unwise (IMO) to "stack" various substances which have not even been through human trials. You are more likely to do serious damage than help yourself.


Dasatanib 3x a year has been ok. You can't quantify effectiveness by lack of health issues but if anyone is curious I am often mistaken for being 10 years younger in my 30s. But I also carry more muscle mass and have blondish hair which hides the gray ones!

It is definitely unwise to stack these particular classes of chemicals... Its not like stacking lysine with C!

#46 DJSwarm

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Posted 21 January 2021 - 03:54 AM

I don't know the original source of the 14 hour number, but it's widely quoted on the net. For example:

 

https://ancientandbr...ick-sugar-habit

 

I also heard it from my doc, who I have a lot of respect for, and who has considerable experience using fasting in her practice.

 

The paper I read tracked restricted diet (AKA fasting) and suggested the main beneficial effects were in the first from 14-24 hours peaking at 16.

https://www.ncbi.nlm...les/PMC6627766/



#47 DJSwarm

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Posted 21 January 2021 - 04:04 AM

My best guess it more like1000mg over the course of an entire day/night.   I'm still alive and not much has changed.  As stated, my panels came out fine, in particular liver was fine as always. 

 

That is an insane amount of D. The human studies I read have mainly use 50 mg to 100 mg over 3 to 5 days. D is not user friendly. Please check before you dose. 100-140mg is the cancer dose. 180mg, if tolerated, was the max dose. https://reference.me...asatinib-342199 Also, extended use has a lot of nasty side effects. I plan to start at 50mg and go no more than 3 days until I learn how well I tolerate it.

 

As a senolytic it is mixed with 500 to 1000mg of Q which maybe what you were thinking of.

 

I'm planning to use 1.2 gms of finestin instead of Q.


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#48 Woody42

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Posted 16 January 2022 - 07:19 PM

Anyone here in the USA have a good source for the Dasanlb ?

 



#49 DJSwarm

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Posted 16 January 2022 - 07:43 PM

I might suggest Theaflavin, Berberine and Fisetin...

 

1) Theaflavin seems to be hitting the same things as Dasatinib without all the side effects. 

 

LE's basis for thinking it works:
 
Scientists set out to identify a compound that would enhance quercetin’s senolytic effects by the same mechanisms as dasatinib, but without the side effects of a cancer drug. The most effective candidate they found was a group of compounds in black tea called theaflavins. In a similar way to dasatinib, theaflavins block an anti-apoptotic protein called BCL-2. If you wonder what BCL stands for, it is “B-cell lymphoma.” A compound that blocks BCL-2 might reduce risk of this common malignancy. In a mouse study, theaflavins demonstrated significant senolytic effects.
 
Noberini R, Koolpe M, Lamberto I, et al. Inhibition of Eph receptor-ephrin ligand interaction by tea polyphenols. Pharmacol Res. 2012 Oct;66(4):363-73.
Noberini R, Lamberto I, Pasquale EB. Targeting Eph receptors with peptides and small molecules: progress and challenges. Semin Cell Dev Biol. 2012 Feb;23(1):51-7.
Ting PY, Damoiseaux R, Titz B, et al. Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1. PLoS One. 2015;10(3):e0121833.
Leone M, Zhai D, Sareth S, et al. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Res. 2003 Dec 1;63(23):8118-21
Han X, Zhang J, Xue X, et al. Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the NRF2 pathway. Free Radic Biol Med. 2017 Dec;113:59-70.
Cameron AR, Anton S, Melville L, et al. Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a. Aging Cell. 2008;7(1):69-77.
Caruana M, Vassallo N. Tea Polyphenols in Parkinson’s Disease. Adv Exp Med Biol. 2015;863:117-37.
Chen SQ, Wang ZS, Ma YX, et al. Neuroprotective Effects and Mechanisms of Tea Bioactive Components in Neurodegenerative Diseases. Molecules. 2018;23(3).
Peng C, Chan HY, Li YM, et al. Black tea theaflavins extend the lifespan of fruit flies. Exp Gerontol. 2009;44(12):773-83.
Aizawa T, Yamamoto A, Ueno T. Effect of oral theaflavin administration on body weight, fat, and muscle in healthy subjects: a randomized pilot study. Biosci Biotechnol Biochem. 2017;81(2):311-5.

 

2) Berberine is a potent mTOR1 inhibitor without R's nasty side effects.

 

Berberine sensitizes rapamycin‑mediated human hepatoma cell death in vitro 

 

Recent research has demonstrated that berberine has anticancer activity against various types of cancer, mediated through the suppression of mammalian target of rapamycin (mTOR). The present study aimed to investigate the in vitro synergistic anticancer effect of combined treatment of rapamycin at various concentrations (0, 10, 50, 100 and 200 nM) and berberine (62.5 µM) in SMMC7721 and HepG2 hepatocellular carcinoma (HCC) cell lines, and the potential underlying molecular mechanism. The combined use of rapamycin and berberine was found to have a synergistic cytotoxic effect, with berberine observed to maintain the cyotoxic effect of rapamycin on HCC cells at a lower rapamycin concentration. Moreover, the cells treated with the combination of the two agents exhibited significantly decreased protein levels of phosphorylated (p)‑p70S6 kinase 1 (Thr389), the downstream effector of mTOR, compared with the cells treated with rapamycin or berberine alone. Furthermore, overexpression of cluster of differentiation (CD) 147, a transmembrance glycoprotein associated with the anticancer effects of berberine, was found to upregulate p‑mTOR expression and inhibit cell death in SMMC7721 cells co‑treated with rapamycin and berberine. In conclusion, the findings of the present study suggest that the combined use of rapamycin and berberine may improve HCC therapy through synergistically inhibiting the mTOR signaling pathway, which is at least in part, mediated through CD147.

 

Looks like berberine maybe a cheaper and safer mTOR1 inhibitor all on its own: Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression  BBR extended the lifespan of chemotherapy-treated mice and naturally aged mice by ~52% and ~16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti-aging medicine.  

 

More fun reading Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway ("...new insight into berberine’s molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.)  Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling (We find BBR caused ALL (Acute Lymphoblastic Leukemia) cell death by inducing autophagy. We also investigate the underlying mechanism responsible for BBR-induced autophagy. The findings will provide crucial insight into the application of BBR on ALL treatment.)

 

Looks like probably liposomal berberine is needed to improve absorption, or, maybe just the right microbiome: Transforming berberine into its intestine-absorbable form by the gut microbiota; or, if you have a lab; d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble form of vitamin E and is comprised of a hydrophilic polar head and a lipophilic alkyl tail resulting in amphiphilic properties for improving bioavailability.

 

3) Fisetin is effective all by its self and has no nasty side effects. (too much evidence to post - see the fisetin thread.)


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