731 replies to this topic

[Longevitarian]

Hi Mikey'

 

Your experience with D is trully puzzling and enlightening at the same time. Specifically,

your observation regarding heart sensations are similar to my but the timeline is different.

In my case the strange cardiac sensation started about 1.5 month ago , almost 5 months

after DQF intervention.

 

The cardiac sensation started within a week after I started to take my maintenance therapy,

with several supplements plus lamisil (antifungal). Before , I have been avoiding supplements,

but have had 2 other short interventions , which themselves had no cardiac effects. Only

after loading on antioxidants, niacin, omega 3 and statin. The effect was very strong

initially (level 4 out of 10),decreased steadily to lets say level 1.5 - 2 about 2 weeks ago

when I discontinued everything within 4 days. Then I resumed lamisil only which causes

cardiac discomfort level oscillating between 0 - 0.5 . Very small, but not completely gone.

 

I am still analysing it , so I cannot exactly tell what is the cause, but it may be that it is removal

of the senescent cells by the immune system and hart remodelling. This process may

be have been originally started by the DQF intervention due to enhacement of the immune

system which have been triggered to fully act by the supplements I stared to take 1.5 month

ago.

 

Originally I attributed this effect to lamisil which is known to cause cardiac complications

in some individuals, but at this moment , I see that this may be less related to lamisil and

more likely to the deayed stimulation of the immune system by the supplements

after DQF intervention. Which would make it similar to what you have experienced....

 

Thanks for sharing your experience.

 

[mikey]

You're welcome and thank you.

 

I experienced some oddly disturbing heavy pulsing of my heart beat that I related to Dasatinib after reading about an increased QT interval with Nilotinib, but which could also happen with high doses of Dasatinib. (I read this somewhere. I don't have the reference at hand.)

 

I have had my share of odd heart issues. Many years back my doctor said that I had a murmur, which doesn't manifest currently.

 

I began experiencing atrial fibrillation (afib) when I was about 25. It kept on a number of months with a doctor putting me on Digoxin to regulate my heart beat. I quit the medication after a month because I prefer not to use medications. Somehow the afib disappeared for years, then returned when I was in my '40's.

 

I had no good answers for it, except that my acupuncurist could stop it and he gave me a Chinese herbal tea that stopped it most of the time, not all of the time.

 

In the '90's studies started appearing that showed that high dose omega-3's reduced the incidence of arythmias and afib.

 

I found that if I take 3,000 to 4,000 mg of EPA/DHA, which I get from a tablespoon of Carlson's The Very Finest Fish Oil, I experience almost no afibs. If they happen, it could be a 30-second flutter three times a year, rather than a full-on afib event that lasts an hour or so - which used to happen 10-15 times a year.

 

Since I am of 3/4 Irish descent, which likely means that genetically I am programmed to get a lot of fish oil, I hypothesize that my afib was just a manifestation of a deficiency of the essential fat, omega 3.

 

The disturbing heart beat that I experienced during the eight or so days after using 300 mg of Dasatinib was not an afib. It was something else, which is why I wonder that it may have been an effect on the QT Interval.

 

I welcome comments/insight.

Edited by mikey, 06 April 2017 - 01:40 AM.

[Logic]

The talk of heart issues rang a worrying bell:

A shortage of Frataxin is the cause of Human Friedreich Ataxia.
it also causes upregulation of Beclin1 which regulates genes in a very similar way to senolytics.
I haven't looked into this properly and don't know that Dasatinib could actually cause low Frataxin and/or temporary Friedreich ataxia at high doses, but thought it best to post now so that everyone could look into it..!

https://www.google.c...chrome&ie=UTF-8

 

Lowering Frataxin to just the right level also extends lifespan in nematodes etc in which it has been tested.
It would seem that lowering the iron and thus iron-sulfur molecules in mitochondria is also involved, not just its senolytic effect:

https://www.google.c...ataxin Beclin&*

 

Again it would seem that the devil may be in the dosage if there is anything to this?

The bell rang because of my posts here:
http://www.longecity...lthspan/page-15

NB from my last post there:

• Vit D should be optimal during senolytic treatment IMHO.  Not only because of its effect on Beclin 1, but also due to the immune system 'calling for vit D' when it finds a pathogen, in order to kill it. That's something that is likely to be more prevalent during treatment and why I also recommend VCO.  NB that the RDA of vit D has been ...'underestimated..?' by a factor of 10!
• Gingko biloba I also find very interesting.  not only because of  upregulating Beclin-1, but also because it is a vasodilator, so it will get senolytics deeper into tissues where blood flow may not be optimal.  There are also studies showing a 25% increase in rat lifespan from GB.
• There is a lot of good info in that thread other than the above.

GoogleSiteSearch in the Search menu (top) is your friend!  

Edited by Logic, 06 April 2017 - 02:26 AM.

[Longevitarian]

Hi Mikey , Hi Logic'

 

Actually , I was going to post next installment of the experiences with DQF

related to the intervention I did over half a year ago. However , I had problem

classifying the heart sensation (which I call CARDIAC SENSITIVITY).

I could not figure out whether it was indeed related to the DQF intervention,

or it was for other, unrelated reasons.

This delayed my post .......At this moment , I am almost certain that the

DQF was part of the "problem" and it was probably caused in combination

with later interventions.

 

Interestingly , first indication of the cardiac sensitivity started at a time (half

a year after DQF intervention)  when I had echocardiogram,(about a week

after I started supplements with niacin, omega 3, multivitamins vitamins ,

statin , melatonin . That moment was also 3 days after I started lamisil.

and coincided with the echocardiogram procedure. Probably started earlier,

but I noticed it only on the day of the echocardiogram.

It was very intense almost painful(level 4 out of 10).especially when the

ultarsound technician applied the probe to my chest

I almost wanted to push him away, to stop the procedure, it was unbearable,

and it radiated from the chest area directly above heart apex...(easy to localise).

The echocardiogram procedure was by pure coincidence at the same time as

the symptoms  started and unrelated  to DQF intervention. Just had an

opportunity to do it. So I did.

 

The cardiac sensitivity continued since then steadily decreasing ......

 

Supprisingly the cardiologist did not find any pathology ...everything in

almost perfect order with exception with tiny irreguralities with the ventricles.

And he dismissed it as probably psychosomatic reaction to the applied probe.

 

I am not very worried about this (cardiac sensitivity) sensation ...

and I expect that it is a delayed but a positive sign (marker)of the

action of DQF in combination with the supplements.

And it acts at the cellular and intarcellular level.

 

I am waiting for the symptoms to disappear completely before I order

another echocardiogram and angiography. This is to get whole

picture of what is happening (if anything will be visible).

 

My take on this is as follows .....If the heart was being somehow repaired

(eg removal of the senescent cells and remodelling of the tissue) I would

expect this kind of symptoms to show up .....

Is it what happens? ....I don"t know ,time will show....

But for sure , I am not very concerned. The symptoms of the cardiac sensitivity

are almost gone despite taking lamisil.....

On the other hand I have not been taking any other medications nor

supplements for last two weeks .....

What will happen when I start taking them again? Again I don't know.....

Have been delaying that moment until the symptoms will completely

disappear.

So DQF project is still a work in progress despite it passed more than

half a year since I started it.....

 

With being the Experimental Test Pilot things usually don"t progess in a linear way....

usually there is lots of unexpected stuff happening ....the DQF is not exception here.

 

Cheers

Edited by Longevitarian, 06 April 2017 - 03:54 AM.

[mikey]

 

The bell rang because of my posts here:
http://www.longecity...lthspan/page-15

NB from my last post there:

• Vit D should be optimal during senolytic treatment IMHO.  Not only because of its effect on Beclin 1, but also due to the immune system 'calling for vit D' when it finds a pathogen, in order to kill it. That's something that is likely to be more prevalent during treatment and why I also recommend VCO.  NB that the RDA of vit D has been ...'underestimated..?' by a factor of 10!
• Gingko biloba I also find very interesting.  not only because of  upregulating Beclin-1, but also because it is a vasodilator, so it will get senolytics deeper into tissues where blood flow may not be optimal.  There are also studies showing a 25% increase in rat lifespan from GB.
• There is a lot of good info in that thread other than the above.

Agree! The all-too-low 2010 RDA for vitamin D was set by a corrupt Institute of Medicine that had two doctors on the panel that are working with drug companies to make vitamin D drugs. It is in their interest for people to be deficient in vitamin D.

 

Vitamin D is generally optimal when the blood test is within the 60-100 ng/dl for D3. This typically requires 8,000-10,000 IU/day, so that's what I'll target before the next time that I do D&Q. (My vitamin D generally tests in the 50-80 ng/dl range.)

 

Note that equally or perhaps even more important than vitamin D for immune function, is real retinol vitamin A, not beta carotene (BC), as a majority of the population do not convert BC adequately for it to be a substitute for retinol.  Some gene tests show a predictable lack of conversion with certain genes.
 

Vitamin A dosing likely should be higher than vitamin D, as this is the way the two nutrients are found in nature. Cod liver oil has a 5:1 ratio of A to D.

 

Nine studies going back to 1937, say that A and D cancel out each other's toxic effects.
[1] Metz AL et al. The interaction of dietary vitamin A and vitamin D related to skeletal development in the turkey poult. J Nutr. 1985 Jul;115(7):929-35. 

[1] Aburto A et al. The influence of vitamin A on the utilization and amelioration of toxicity of cholecalciferol, 25-hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol in young broiler chickens. Poult Sci. 1998 Apr;77(4):585-93.

[1] Mernitz H et al. Inhibition of lung carcinogenesis by 1alpha,25-dihydroxyvitamin D3 and 9-cis retinoic acid in the A/J mouse model: evidence of retinoid mitigation of vitamin D toxicity. Int J Cancer. 2007 Apr 1;120(7):1402-9.

[1] Masterjohn C. Vitamin D toxicity redefined: vitamin K and the molecular mechanism. Med Hypotheses. 2007;68(5):1026-34.

[1] Xueyan Fu et al. 9-Cis retinoic acid reduces 1alpha,25-dihydroxycholecalciferol-induced renal calcification by altering vitamin K-dependent gamma-carboxylation of matrix gamma-carboxyglutamic acid protein in A/J male mice. J Nutr. 2008 Dec;138(12):2337-41.

[1] Morgan AF, et al. A comparison of the hypervitaminoses induced by irradiated ergosterol and fish liver oil concentrates. J Biol Chem. 1937;120(1):85-102.

[1] Clark I, Smith MR. Effects of hypervitaminosis A and D on skeletal metabolism. J Biol Chem.

1963;239(4):1266-71.

[1] Clark I, Bassett CAL. The amelioration of hypervitaminosis D in rats with vitamin A. J Exp Med.

1962;115:147-56.

[1] Callari D, et al. Retinoic acid action on D3 hypervitaminosis. Boll Soc Biol Spec. 1986 Jun 30;62(6):835-41.

 

Since ~54% of the US population is deficient in vitamin A, it is wise to also take supplement retinol when one is supplementing vitamin D, as the two vitamins not only apparently protect us from each other's potential for toxicity, but they exhibit numerous complementary characteristics in supporting immune health, bone health, cardiovascular health and more.

 

Perhaps someone here can find data showing a potential role for vitamin A in senolytic treatment?

[Nate-2004]

You have a point Mikey. I got my genome data back from 23 and me and discovered I'm one of the people who don't convert beta carotene to Vitamin A very well so I added 10k IU of A a day along with the 4k IU of D I have taken for years. Luckily all my other genes are mostly good, FOXO3 being the highlight of that good, I'm homozygous GG which is awesome for longevity. I also have a couple other longevity genes. Turns out I don't have the MTHFR mutation luckily so I convert folate well. I also checked anything to do with B vitamins, those are good. Got lucky on those fronts, but essential tremor still sucks, wish they knew the gene for that. I also apparently have 3 genes associated with autism, not surprised.

Edited by Nate-2004, 06 April 2017 - 01:23 PM.

[Nate-2004]

Speaking of genes, I read this on the Wikipedia page regarding dasatinib:

 

Responses were seen in patients with all BCR/Abl genotypes, with the exception of T315I mutation, which confers resistance to dasatinib, nilotinib and imatinib in vitro.

 

I can't seem to find anything about these genotypes or mutations in the genotyping I got back from 23 and Me. How do I find out whether I fall into this category? Does this affect whether it works as a senolytic or just whether it inhibits tyrosine kinase?

 

What's worrisome to me is that the Wikipedia page mentions absolutely nothing about senolytics.

[Logic]

Update:

 

1. I wouldn't recommend dosing as high as 4 x 100gm/24hours = 400mg

2. I found that dosing every 6 hours was less harsh and more effective

3. I had no flu symptoms but had high temperature once half-life ended

4. Similarly to before I feel tissue shrinkage and somewhat rejuvenated

 

Next time, I may try 3 x 100mg over 18 hours i.e. dosing every 6 hours = 300mg

Or spreading it out with 6 x 70mg over 36 hours, dosing every 6 hours = 420mg

 

I found that intense intake for a short period was more beneficial than slower intake over a longer period of time. Logic probably is onto something when he says that we must maintain product suspended in our bloodstream for a longer period than 5 or 6 hours. Keeping levels high makes a difference in my perceived result. I was led to try this by his convincing argument, but also by Mikey's trial with high dose single intake of 300mg which had violent impact but also some lasting benefits. High doses might be most useful, but spreading them out in 6 hour intervals makes them less harsh in their consequences. It also allows the patient to stop intake at any stage if they feel it's too much. However, please note that, in my modest experience, the strongest side-effects happen once the half-life is over and you're starting to experience the consequences.

 

DareDevil

 

Thx for the report Daredevil

It occurred to me that the half-life of Quercetin should also be considered.

 

...The average terminal half-life of quercetin is 3.5 h. The total recovery of C-quercetin in urine, faeces and exhaled air is highly variable, depending on the individual (Moon et al. 2008). These results are consistent with those of other authors who have measured quercetin absorption and appearance in plasma after ingesting the pure quercetin aglycone as well as various glycoside forms contained in foods such as shallots, onions and apples (Egert et al. 2008). Additional literature indicates that isoquercetin (glycosylated quercetin) is more completely absorbed than is quercetin in the aglycone form, and that the simultaneous ingestion of quercetin with vitamin C, folate and additional flavonoids improves bioavailability (Manach et al. 2005, Harwood et al. 2007)...

 

...Quercetin accumulates in the outer and aerial tissues (skin and leaves) because biosynthesis is stimulated by exposure to sunlight. Human subjects can absorb significant amounts of quercetin from food or supplements, and elimination is quite slow, with a reported half-life ranging from 11 to 28 h (Conquer et al. 1998, Manach et al. 2005)...

 

...the bioavailability of quercetin increases with the co-ingestion of fat (Guo et al. 2013)...

https://www.ncbi.nlm...rients-08-00167

 

???
From that it seems food sources have a longer half life than supps?
The supplied references will have to be followed to be sure.
Here is a link to Schi-Hub that gives these papers for free:
http://www.sci-hub.io/

 

And a link to the Moon et al paper, the 1st reference above:
http://sci-hub.cc/ht...02/bdd.605/full
A quick scan of the paper's graphs shows low bioavailability and great variance between individuals...

The Quercetin I have on hand contains Bromelain to enhance absorption.
Properties and Therapeutic Application of Bromelain: A Review:

https://www.ncbi.nlm...les/PMC3529416/
 

Good:
...Bromelain is found to increase the expression of p53 and Bax in mouse skin, the well-known activators of apoptosis [54]. Bromelain also decreases the activity of cell survival regulators such as Akt and Erk, thus promoting apoptotic cell death in tumours...

 

Bad due to D's anti coagulation effects:

...Bromelain influences blood coagulation by increasing the serum fibrinolytic ability and by inhibiting the synthesis of fibrin, a protein involved in blood clotting...

 

Unknown:
...In vitro experiments have shown that Bromelain has the ability to modulate surface adhesion molecules on T cells, macrophages, and natural killer cells and also induce the secretion of IL-1β, IL-6, and tumour necrosis factor α (TNFα) by peripheral blood mononuclear cells (PBMCs) [37–43]. Bromelain can block the Raf-1/extracellular-regulated-kinase- (ERK-) 2 pathways by inhibiting the T cell signal transduction [44]. Treatment of cells with bromelain decreases the activation of CD4 (+) T cells and reduce the expression of CD25...

Edited by Logic, 06 April 2017 - 09:24 PM.

[niner]

I just got my package of Dasatinib today, so this is a good time to repost the Dasatinib Product Information Monograph.  It contains all the safety information you're likely to need.  I think the biggest danger is bleeding.  D and drugs like it will bring about premature apoptosis of platelets, as well as alter their function.  The resulting low level of platelets is called thrombocytopenia.  Patients have died from hemorrhage on D, so keep an eye out for bleeds.   Before you take any D, I'd recommend stopping any drugs or supplements that can affect bleeding for at least a week.   Aspirin, even at low dosage, is the worst offender.  I'd stop fish oil as well.   D is metabolized by CYP3A4.  You should avoid 3A4 inhibitors while using D.  (ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice, St. John's Wort, others)
 
Further drug interaction cautions:

Concomitant use of dasatinib and a CYP3A4 substrate may increase exposure to the CYP3A4 substrate. Therefore, caution is warranted when dasatinib is coadministered with CYP3A4 substrates of narrow therapeutic index, such as astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, dihydroergotamine) (see section 4.5).  The concomitant use of dasatinib and a histamine-2 (H2) antagonist (e.g. famotidine), proton pump inhibitor (e.g. omeprazole), or aluminium hydroxide/magnesium hydroxide may reduce the exposure to dasatinib. Thus, H2 antagonists and proton pump inhibitors are not recommended and aluminium hydroxide/magnesium hydroxide products should be administered up to 2 hours prior to, or 2 hours following the administration of dasatinib (see section 4.5).

The largest dosage form produced for Dasatinib is 140 mg.  You should probably think of this as the upper limit for 24 hours.  I plan to start lower than that, maybe 50 mg, eventually raising the dose as I come to understand how I react to it.  We'll have to experiment with dosage and duration, although we don't have very good ways to evaluate senolytic effects.  I have some actinic keratoses that I'm hoping to see an improvement in.  Time will tell.
 
Ordinary quercetin has terrible pharmacokinetics.  It's rapidly metabolized, similar to resveratrol.  There are a couple formulations that should help significantly.  I'm going to try EMIQ (ref), to see if it works.  Anthony Loera distributed a liposomal version a while back, but I don't know if he's selling it now or not.  I'm interested in Honokiol and Mebendazole, based on Fafner55's results.
 

Edited by niner, 07 April 2017 - 03:14 AM.

[Andey]

 

 
Ordinary quercetin has terrible pharmacokinetics.  It's rapidly metabolized, similar to resveratrol.  There are a couple formulations that should help significantly.  I'm going to try EMIQ (ref), to see if it works.  Anthony Loera distributed a liposomal version a while back, but I don't know if he's selling it now or not.  I'm interested in Honokiol and Mebendazole, based on Fafner55's results.
 

 

  Is it not  20% bioavalability up to 10 hour half life ? Am I missing something ?

 

Sorry, just saw the discussion above

Edited by Andey, 07 April 2017 - 07:12 AM.

[jmorris]

Regarding navitoclax toxicity to Sertoli cells and possible solutions:

 

We know that navitoclax works by inhibiting BCL-2, BCL-XL and BCL-W. These three proteins in turn are responsible for blocking the pro-apoptotic mitochondrial pore-forming proteins BAX and BAK. The balance between these pro- and anti-apoptotic proteins is the deciding factor of whether or not a senescent cell lives or dies.

 

Sadly, testicular Sertoli cells also exist in a state where this balance is critical to survival and also express some of these pro-apoptotic proteins. Are Sertoli cells senescent? No, but they do bear some of the markers of senescence. For example, see the paper below, where it is found that Sertoli cells are found to express p16Ink4a, a marker of senescence:

 

Nielsen, G. P., A. O. Stemmer-Rachamimov, J. Shaw, J. E. Roy, J. Koh, and D. N. Louis. “Immunohistochemical Survey of p16INK4A Expression in Normal Human Adult and Infant Tissues.” Laboratory Investigation; a Journal of Technical Methods and Pathology 79, no. 9 (September 1999): 1137–43.

 

It got me to thinking: Is there a way to selectively down-regulate these pro-apoptotic proteins just in Sertoli cells?

 

The answer appears to be yes.

 

Direct modulation of BAX levels in sertoli cells by horomones:

 

Le Goff, Dominique, Céline Viville, and Serge Carreau. “Apoptotic Effects of 25-Hydroxycholesterol in Immature Rat Sertoli Cells: Prevention by 17beta-Estradiol.” Reproductive Toxicology (Elmsford, N.Y.) 21, no. 3 (April 2006): 329–34. doi:10.1016/j.reprotox.2005.09.003.

 

I this paper, treatment of SCs with 25-hydroxycholesterol was found to boost levels of BAX mRNA. However, they also found that treatment with physiological concentrations of 17beta-estradiol (estrogen) prevented the apoptosis!

 

 

Lucas, Thaís F. G., Carine Royer, Erica R. Siu, Maria Fatima M. Lazari, and Catarina S. Porto. “Expression and Signaling of G Protein-Coupled Estrogen Receptor 1 (GPER) in Rat Sertoli Cells.” Biology of Reproduction 83, no. 2 (August 1, 2010): 307–17. doi:10.1095/biolreprod.110.084160.

 

In this one, the authors found that 17beta-estradiol treatment of SCs decreased BAX and increased BCL2 expression.

 

 

Lucas, Thaís Fg, Maristela T. Pimenta, Raisa Pisolato, Maria Fatima M. Lazari, and Catarina S. Porto. “17β-Estradiol Signaling and Regulation of Sertoli Cell Function.” Spermatogenesis 1, no. 4 (October 2011): 318–24. doi:10.4161/spmg.1.4.18903.

 

There are three estrogen receptors: ESR1 and ESR2 which are nuclear receptors and GPER which is a G-protein-coupled receptor found in the plasma membrane. In the above paper, the find that activation of the GPER "increases expression of the anti-apoptotic protein BCL2 and decreases the expression of pro-apoptotic protein BAX". So, only one of the three subtypes of estrogen receptor are important for regulating apoptosis in Sertoli cells.

 

Royer, Carine, Thaís F. G. Lucas, Maria F. M. Lazari, and Catarina S. Porto. “17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells.” Biology of Reproduction 86, no. 4 (April 2012): 108. doi:10.1095/biolreprod.111.096891.

 

In this one, the authors use a GPER specific estrogen agonist to study the anti-apoptotic effects of estrogen.

 

 

Simões, V. L., M. G. Alves, A. D. Martins, T. R. Dias, L. Rato, S. Socorro, and P. F. Oliveira. “Regulation of Apoptotic Signaling Pathways by 5α-Dihydrotestosterone and 17β-Estradiol in Immature Rat Sertoli Cells.” The Journal of Steroid Biochemistry and Molecular Biology 135 (May 2013): 15–23. doi:10.1016/j.jsbmb.2012.11.019.

 

In this paper, the authors study not only estrogen but also DHT and find that they both have anti-apoptotic effects.

 

 

So there you go, a Sertoli cell specific way to down regulate BAX and possibly avoid the negative effects of navitoclax on the testes. It helps a lot that 17-beta estridiol (estrogen) is so easy to get (birth control). Now, as a man, I would normally think that estrogen is the last thing that I want in my body. However, if we were to combine estradiol with navitoclax for just a day or two every once in a while, I'm sure the estrogen effects would be negligable or even more likely, zero. Remember that some level of estrogen is healthy in males and that when men want to grow breasts that they also need to take something that inhibits testosterone as well.

 

My next question would be, would we need to take 17-beta-estridiol or would it be better to take something that was specific for the GPER receptor. From Tocris, here are the options:

 

Tocris:

 

https://www.tocris.c...81#.WNTP_xPytp8

 

    17-β-Estradiol (good)

 

    G-1 (very specific but maybe hard to get)

 

    ICI 182,780 (also hard to get)

 

    Quercetin (No thank you: shitty bioavailabilty, plus not specific)

 

    Tamoxifen citrate (Possibly better?)

 

Tamoxifen and 17-β-Estradiol certainly look the most interesting and both are trivial to obtain. I need to do more reading on Tamoxifen. Tocris lists it as an "Estrogen receptor antagonist/partial agonist... Also high affinity agonist at the membrane estrogen receptor GPER." So maybe β-Estradiol might be better or maybe not.

 

 

TL;DR:

 

Take Estradiol or possibly other estrogen GPCR agonists to selectively down-regulate pro-apoptotic proteins in sertoli cells may be a way of avoiding sertoli cell apoptosis while taking drugs like navitoclax known to kill sertoli cells by that pathway. 

[Nate-2004]

I didn't see anything about alcohol interactions. I have a couple dates coming up over the next few days.

 

I just got mine. 

 

Isn't bioperine (piperine) a CYP3A4 inhibitor? They combine that with curcumin to make it more bioavailable. I should pretty much stop nearly everything while I'm doing this I guess.

 

I posted this earlier but do you guys think 75mg for 5 days (3500mg Quercetin) is plenty for a 42 year old?

[Nate-2004]

Oh also, sorry for all the posts but another point is if you're like me and still drink hydrogen water made with magnesium (because every time I think it's not doing anything I quit and then my back pain comes back, weird synergy with infrared light), you'll want to drink it 2 hrs before or after taking dasatinib. Apparently magnesium hydroxide is an issue.

 

Also avoid grapefruit juice, chamomile, cat's claw, echinacea, licorice. Glad I read that because I take chamomile extract at night for its apigenin.

Edited by Nate-2004, 07 April 2017 - 04:42 PM.

[Valijon]

I thought we had decided on 75mg every 6 hours for one day every 5 days?

[Nate-2004]

I thought we had decided on 75mg every 6 hours for one day every 5 days?

 

I hadn't heard that one. I was doing 75mg every 6 hrs *for* 5 days every 6 months to a year.

 

I say we make a poll or group up into different dosings.

 

What's the official recommended dose from Bristol Meyers, vs the dose intended for senolytic use vs the doses people are wanting to experiment with?

 

So far we have:

 

1) 75mg twice a day for 5 days every 6 months.

2) 75mg every 6 hrs every 5 days. (for how long?)

3) ?

[Rocket]

 

I thought we had decided on 75mg every 6 hours for one day every 5 days?

 

I hadn't heard that one. I was doing 75mg every 6 hrs *for* 5 days every 6 months to a year.

 

I say we make a poll or group up into different dosings.

 

What's the official recommended dose from Bristol Meyers, vs the dose intended for senolytic use vs the doses people are wanting to experiment with?

 

So far we have:

 

1) 75mg twice a day for 5 days every 6 months.

2) 75mg every 6 hrs every 5 days. (for how long?)

3) ?

 

 

Why aren't people just copying the mouse study that was 1 larger dose a single time?

 

I got back the results of my lab rat's blood work and the WBC count is still slightly elevated about a month post experiment.
 

[Nate-2004]

 

 

I thought we had decided on 75mg every 6 hours for one day every 5 days?

 

I hadn't heard that one. I was doing 75mg every 6 hrs *for* 5 days every 6 months to a year.

 

I say we make a poll or group up into different dosings.

 

What's the official recommended dose from Bristol Meyers, vs the dose intended for senolytic use vs the doses people are wanting to experiment with?

 

So far we have:

 

1) 75mg twice a day for 5 days every 6 months.

2) 75mg every 6 hrs every 5 days. (for how long?)

3) ?

 

 

Why aren't people just copying the mouse study that was 1 larger dose a single time?

 

I got back the results of my lab rat's blood work and the WBC count is still slightly elevated about a month post experiment.
 

 

 

Is that a good thing? Isn't an elevated white blood cell count a sign of inflammation at best?

[Andey]

 

 

Why aren't people just copying the mouse study that was 1 larger dose a single time?

 

I got back the results of my lab rat's blood work and the WBC count is still slightly elevated about a month post experiment.
 

 

 

What WBC subpopulations (lymphocytes, neutrophiles, monocytes etc) went up ? Is it elevated above normal range or above your 'base' levels ?

 

 

Edited by Andey, 07 April 2017 - 05:11 PM.

[Rocket]

 

 

 

Why aren't people just copying the mouse study that was 1 larger dose a single time?

 

I got back the results of my lab rat's blood work and the WBC count is still slightly elevated about a month post experiment.
 

 

 

What WBC subpopulations (lymphocytes, neutrophiles, monocytes etc) went up ? Is it elevated above normal range or above your 'base' levels ?

 

 

A couple of ticks above normal baseline (non illness) that I've watched over a couple years. Not much, but it is a little blip. I don't know the breakdown you're asking for. It could be coincidence that this little spike in measured readings just happened post experiment. I wanted to do it much sooner but always too busy to fast for a blood test.
 

Edited by Rocket, 07 April 2017 - 06:39 PM.

[Nate-2004]

I've never asked this or seen it specifically answered before but why D+Q? I realize it's funny asking this after I started my first dose already but. I realize Q is supposedly senolytic as far as endothelial cells go and D is supposedly senolytic as far as human fat cell progenitors go. Why together? Is it because they're synergistic in some way? Does taking them together result in eliminating more or other senescent cells?

[Logic]

Dasatinib Group buy progress report:

Lab, 7 April 2017 at 02:39:  "All US bound packages left my hands. Got tracking nos. will punch them in

morning" 

I have not yet received any tracking # for anyone but the 5 recipients whose packages were posted earlier this week.

I will post when possible as I am traveling (work, Africa) atm, but there is a chance you might receive your package before your tracking #

Enjoy your research.  

Please log your experience and any pertinent medical data you may have.

 

• Should I start a 'Dasatinib+Quercetin:Senolytic. Research results' thread? 
• What would you put on a questionnaire for dasatinib research?
• I will redact any PMd results for those who choose to remain anonymous and post directly?
• A poll?
• This thread would have to be a joint effort to keep it on point, orderly and useful?

Navitoclax:

 

 

It's also time remind everyone of the obligatory disclaimer posted earlier.

 

Disclaimer:
I am not a doctor, nor do I claim to have any formal medical background.
I am not liable, either expressly or in an implied manner, nor claim any responsibility for any physical or emotional problems that may occur directly or indirectly from the use of any supplement or medication, or advice on this forum.
Products currently covered by valid patents are offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Section 68B of the Patents Act of 1953 in New Zealand; (vi) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (vii) such similar laws and rules as may apply in various other countries. In the European Union, equivalent exemptions are allowed under the terms of EC Directives 2001/82/EC (as amended by Directive 2004/28/EC) and 2001/83/EC (as amended by Directives 2002/98/EC, 2003/63/EC, 2004/24/EC and 2004/27/EC). Any patent infringement issue and resulting liability is solely at buyer's risk.

Please read the warnings and contraindications etc carefully before beginning any research with Dasatinib or any other concomitant, pre or post medication or supplement:

[TaiChiKid]

If the half life of D is roughly 6 hours, then the correct 2nd dose of D should be 1/2 the original dose.  This is because half is still in your system.  Then the level of D will total the original dose.

 

So if you take a dose of 100mg, after 6 hours 50mg will remain in your system. Taking 50mg more will bring you back to the 100mg level again.  Ditto with adding EMIQ Q after 3 hours.

 

IMHO you should wait until all the D is washed out of your system before taking rejuvenating supplements/protocols.  Maybe several days?

[Nate-2004]

Here's a question I didn't think of before taking D over the past nearly 3 days. D is a tyrosine kinase inhibitor, what happens if I take tyrosine? I have it mixed in with the bacopa/ginko capsule I take twice a day as a nootropic.

[Logic]

Dasatinib storage:
 
I for one plan on taking three 50 mg doses of D, 5 hours apart. with the next senolytic session 3 to 12 months later.
This means that the D needs to be stored for a long period of time.

As with most medications, heat, light, air and the moisture in the air are the things that will degrade D.
So here are my thoughts on the proper storage, freezing and thawing of D and other meds, keeping the laws of physics in mind:
 

Thawing:
Moisture in the air will condense on a cold surface. like the droplets formed on a cold glass of water.

If that cold surface happens to be a Particle of D; that is what the moisture will condense on.
So let's imagine you put the N in a jar with an airtight lid and put it in the freezer for long term storage.
Now the powder itself eventually cools down to around -20C.
When you take the jar out, but leave it sealed moisture will form on the cold outer surface of the jar.
That's fine, but if you open the jar while the powder is cooler than ambient temperature; then the powder itself becomes a cold surface on which moisture condenses and you don't want that.
ie:  You need to wait for the jar and powder to warm up to ambient temperature before opening the jar.

 

Freezing:

Now lets assume you take out your month's supply, reseal the jar, and put it back in the freezer.
The moisture in the air in the bottle will condense on the surface that is coldest 'firstest'; the glass wall of the jar.
The powder touching the glass wall of the jar will be affected by this condensation...
Also the condensed moisture /water on the glass above the powder may run down and affect more than just the particles touching the glass surface.

Putting the D in small ziplock bags and squeezing all the air out, before putting it in airtight jars will add a 2nd layer of protection here.
And/or you could absorb the moisture in the air in the jar with silica gel sachets before cooling it down again.
Also the less air/free space in the sealed container; the less air and water vapour there will be.

ie: Don't use a jar that is bigger than it has to be.

 

NB: As cold air sinks (denser), the coldest area in your freezer is the lowest area.

Because this is so difficult to explain and confusing to most, most medication manufacturers simply recommend keeping the medication in a cool, dry place.
I think the proper thawing and pre freezing, packaging and/or drying of D, is a good idea.
 
Because light also degrades meds and supps; a cool, dry and dark storage area is recommended.

Fortunately you don't get much darker than a closed freezer, unless its light isn't going off as it should.

[niner]

Here's a question I didn't think of before taking D over the past nearly 3 days. D is a tyrosine kinase inhibitor, what happens if I take tyrosine? I have it mixed in with the bacopa/ginko capsule I take twice a day as a nootropic.

 

There are some 90 known tyrosine kinases, of which D inhibits only a handful.  Tyrosine kinases have a recognition domain that looks for specific features of the protein that they phosphorylate, so I think it's unlikely that they would recognize free tyrosine at any more than a low level.  Thus, I wouldn't expect much of anything to happen if you took tyrosine with D, but to be on the safe side, I'd still skip it.  You probably shouldn't schedule D experiments during times when you have to work, at least until you know how you react to it.  If you aren't working, you could presumably skip the noots for a couple days. 

[Nate-2004]

Well tonight's the last night for several months anyway. I did 75mg D + 1500mg Q twice per day for 3 days with an extra dose today.

 

Honestly while I did experience a very mild drop in energy, I don't have anything else to report.

 

I dropped a few supplements while taking it and I didn't go to the gym or use the sauna (to avoid GH/IGF-1 increases).

 

The supplements I did take were Vitamin D, some A, sulforaphane, garlic, [L-theanine, taurine, magnesium, inositol] (bracketed is my essential tremor cocktail), bacopa/tyrosine/ginko mix (mentioned above), and I also took honokiol at night which I usually do because it improves my sleep pretty well. Melatonin too. I always do melatonin, I'm an insomniac otherwise.

 

I did not take NR.

 

Yeah I know, I take a *f**kload of supplements. I figured I would one day when I was older. Luckily I have so much of it in bulk.

Edited by Nate-2004, 10 April 2017 - 03:40 AM.

[Valijon]

We need a better way to log our experiences. How did you feel while taking the d and q Nate? I'm really curious to see how you feel over the next few days.

[Nate-2004]

We need a better way to log our experiences. How did you feel while taking the d and q Nate? I'm really curious to see how you feel over the next few days.

 

Like I said, just a mild drop in energy that may or may not be attributable to the D+Q. I am curious to find out how I feel the next few days. 

 

Not sure if I should expect much. I'm carrying two major longevity genes, one of them is homozygous GG on the FOXO3 one which may mean I'm not dealing with as many senescent cells as other people might be at my age.  If this is all we can do right now, targeting only fat progenitor and endothelial cells then I'm not expecting much until we have better drugs targeting more selectively on a wider range of senescent cells.

Edited by Nate-2004, 10 April 2017 - 04:25 AM.

[mikey]

 

 

 

NAC is cheap. I generally take the Jarrow NAC-Sustain @ 1,800 mg a couple-few times a day. Of supplements NAC is one that truly provides protective anti-ageing  benefits.

 

 

NAC driven increase is nothing compared to IV Glutathione. Trust me Ive tried both intensively ) I hardly notice any effect of NAC on inflammation but IV G is definitely noticeable.

Ive nothing against NAC thought it is a good addition to long term stack.

 

 

Where did you obtain your injectable Glutathione?

 

And what dose do you use?

[Ark]

Are their any medications that would interfere or adversely react to Dasatinib?

Edited by Ark, 11 April 2017 - 07:29 PM.