731 replies to this topic

[Rocket]

Who's in for FOXO4-DRI? Depending on how many people we can get the price can be around 400 for each 50mg. If its just a few us us the price will be a little higher. Chroma thinks 100mg is a good starting dose but no one really knows much yet. A couple people seem to be having some effect with a much lower dose.

I'm in!

100mg how often? Once every...?

In the spirit of the original purpose of this thread I will be doing my second round of D+Q in about a week. I think a lot of people gave up too soon... My experience has been positive.

[meatsauce]

I was thinking doing 100mg over about a ten day period. Someone said they felt effects from taking only 5 mg. If that is true then I think 20x that will be worth trying. 

[Andey]

Who's in for FOXO4-DRI? Depending on how many people we can get the price can be around 400 for each 50mg. If its just a few us us the price will be a little higher. Chroma thinks 100mg is a good starting dose but no one really knows much yet. A couple people seem to be having some effect with a much lower dose.

I am in

[mikey]

I would be in if I were more sure of dosage. If I can see some profound effects for a couple/few thousand dollars, I would be in.

[Nate-2004]

Same here. I'd need to know the effective dosage, otherwise $400 for 50mg is excessive if the dosage is more than that per day.

[Andey]

I would be in if I were more sure of dosage. If I can see some profound effects for a couple/few thousand dollars, I would be in.

  Its actually a very sensible idea, but I am afraid we need half a decade to get those numbers from science.

We need to establish some metric to assess and compare effect on biological age from different interventions.

I am nursing the idea to use HRV (heart rate variability) as  proxy for this. Particularly pNN50 as it have quite nice correlation with age on the one hand

and on the other hand could be measured even with camera sensor on mobile phone (which is not true for other HRV measurements)

A lot of things could influence this, particalarly level of fitness. But all other things equal individual could measure pNN50 consequtevitely for a few days before intervention (to get mean value) and get another series after few weeks/months from intervention

Just food for thoughts

 

 

[ClarkSims]

I have been taking C60 OO, for about 3 weeks of every month for the last year. I have been doing fast about once per month for about 18 months now. I started the Q+D after the fast about 6 months ago.  I have started tracking my body temperature, blood pressure, weight, body measurements (done with a tape measure), and doing a urine strip test. I started the urine strip test about 6 months ago, because I have had kidney issues twice in my life, and want to make sure I don't damage my kidneys. There are a few vague mentions on the Internet, that Q, causes kidney stress.

 

http://www.livestron...etin-bromelain/

 

Anyway, enough background. I have noticed two very strong effects. My body temperature is significantly lower: Here are a few weeks of measurements:

96.9F
96.6F
95.8F
96.1F
96.3 F
98.1 F <-------------- diagnosed with a viral infection
97.1F
97.5F
97.4F
97.9F
97.1F
97.5F
97F
96,fF
97,1F
96.8 F
97.2 F
96.8F
97.2F
97.2F
 

One the one day when my temperature was above 98, I had a read sore through, swollen lymph glands, and felt like I was feverish. I was so lethargic, that I stayed home from work. I recovered very quickly. Many people at work were very ill, and remained ill for weeks.

 

(Note that I greped those numbers out of a file that I use for a scratch pad. The real measurements are in emails to myself, which are time consuming to assemble into a time series)

 

The other strong effect that I have noticed is that my body has become super efficient at pulling energy out of food. I don't get hungry when fasting. I have tracked my calorie consumption, and energy expenditure with a fit-bit. I have run about a 500 hundred calorie defect almost every "normal" day since I started tracking the spread. When I exercise or fast, the deficit is closer to 2000 calories. I am about the same wait now, that I was 6 months ago, but my body fat has visibly declined. When I try to narrow the spread by intentionally eating after a hard workout, I can't possibly eat enough. I would get sick if I ate that much food.

 

One last observation. When I fast, I no longer show any keytones, until the morning after the 5th day of the fast. For my early fast, the keytones maxed out the the test strip after 3 days.

 

Has anyone else noticed similar effects?

[ClarkSims]

Here are two snapshots from my android. The first is during my partial fast. I realize now, I should said partial fast previously. The second is from a typical week. I walked a long distance on Friday (I work in Manhattan. I ran errands, and walked to a friend's house). I worked out on Saturday.

Attached Files

•  the_fast.png   167.03KB   12 downloads
•  working_out.png   161.07KB   13 downloads

[StanG]

I managed to buy some D from a poster (thanks again) and, in the meantime, spent several weeks reading the posts. I stopped baby aspirin five days before taking it and all other supplements three days before; but increased my Q(emiq) and D3. I took 41mg once only. Being 74, I felt there had been more time for senescent accumulation than many here. I stopped the gym but increased my Q and D3 for five days afterward.

 

I felt nothing from this but still plan to take this regimen every six months (just because I didn't notice anything this time doesn't mean it didn't "work"). 

[Rocket]

I managed to buy some D from a poster (thanks again) and, in the meantime, spent several weeks reading the posts. I stopped baby aspirin five days before taking it and all other supplements three days before; but increased my Q(emiq) and D3. I took 41mg once only. Being 74, I felt there had been more time for senescent accumulation than many here. I stopped the gym but increased my Q and D3 for five days afterward.

I felt nothing from this but still plan to take this regimen every six months (just because I didn't notice anything this time doesn't mean it didn't "work").

I had good results with 2 consecutive much larger doses. Day 3 I felt ill like the flu but rapidly recovered the next day. After all the infamous mouse experiment was one large dose.

[Vantika]

I had good results with 2 consecutive much larger doses. Day 3 I felt ill like the flu but rapidly recovered the next day. After all the infamous mouse experiment was one large dose.

 

Would you mind elaborating on these results?

[DareDevil]

Hi Stan,

 

I understand your precautionary dosage. So that you know, before my excessive dosing last January, I took the same dose as you regularly for two weeks in January 2016. It was in the form of pharmaceutical prescription Sprycel pills, two per day at 20mg per pill. I did this until my box of 30 pills was gone, taking Quercetin daily also.

 

I found that it had an effect, but wished for even more. That was a total of 600mg over 15 days. A single dose of 40mg isn't probably going to do that much for you, but I understand you wish to ease into this gradually. When the time comes where you decide to up the dosage, taking 80mg shouldn't be as harsh as the 100mg dose that many take. Even 70mg should give a stronger effect. There might be a dosage level at which Dasatinib becomes effective. I did notice positives with 40mg so it's below that for sure, but optimal dosage could be above that. FWIW.

 

DareDevil

[StanG]

Hi Richard

 

I plan to increase to two days at 50mg each. I'm conservative when it comes to my health and I know that D builds up in the body. It also messes up my supplement routine for 8-10 days. Also, it may have a long term affect on stem cells (anybody that can show me differently I'd be gratfully to).

 

Stan

[thedarkbobo]

Hello everyone,

 

Is it available for purchase at this time? Not much - just for me for 1-2 sessions at most needed so around 1-2grams.

 

Thanks,

Peter

[Daniel Cooper]

 

@sthira I note you mentioned taking quercitin during your fast, did you observe an increase in detox symptoms? I added it to the second day of a 2-day fast and seemed to experience more headaches and achiness that I'd normally have anticipated, though I've been a rather lapse in fasting over the last 6 months.  

 

This effect is probably due to Q killing off virii and/or infected cells.  (I dont recall if it has any effect on bacteria)
The same virii that stop senescent cells from dying off in the 1st place..!
Virii inject their own DNA into the DNA strand your cell/s; changing it into a factory for more virrii.
At the same time the virus will modify this hard won 'virus factory' to not be detected as a defective and/or senescent cell, to avoid it being taken out by the immune system.

 

Proof of Querciten's effect/s and why, in large part, its and effective senolytic:
https://www.google.c...chrome&ie=UTF-8

ie:  

Medications like Bavituximab and DRACO which kill of vast swathes of such pathologically modified cells can be considered the most targeted and effective senolytics 'available'.
I expected a spate of research and a clamouring for group buys of these drugs, but somehow this nugget of information seems to have flown right over everyone's heads..!?

ie:  I been sitting here waiting for someone to pick up on this since I first posted it......!?

Someone?  Anyone!??  Heeeelp! I feel so lonely here!

 

 

 

I'm shocked that research on DRACO seems to have ground to a halt.

 

Group buy?  

[Fafner55]

More promising results on the benefits of dasatinib as a senolytic, this time for reversing age-related bone loss.

 

“Targeting cellular senescence prevents age-related bone loss in mice” (2017) https://www.nature.c...ll/nm.4385.html

.... The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function4, enhances insulin sensitivity3, and reduces frailty7, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

 

As an alternative to the genetic approach and one potentially applicable to humans, we have exploited the dependence of senescent cells on specific prosurvival pathways and identified a combination of senolytics–dasatinib (D; an FDA-approved tyrosine kinase inhibitor28) and quercetin (Q; a flavanol present in many fruits and vegetables29)—that specifically kills senescent cells without affecting proliferating or quiescent, differentiated cells5,6. To test this approach, 20-month-old male C57BL/6 mice were randomized to either vehicle or D + Q treatment once monthly for 4 months (Fig. 2a). D + Q treatment led to significantly lower p16Ink4a mRNA in bone (Fig. 2b), as well as a lower percentage of senescent osteocytes, as assessed by a SADS assay (Fig. 2c), in D + Q–treated mice relative to vehicle treated mice. The systemic clearance of senescent cells with D + Q was verified by demonstrating lower p16Ink4a mRNA (Fig. 2d) and SA-β-gal-positive cells (Fig. 2e–g) in adipose tissue of 24-month-old D + Q–treated mice. As in the INK-ATTAC model, D + Q administration for 4 months resulted in substantially better spine trabecular bone microarchitecture than in vehicle-treated controls (Fig. 2h–m), with similar improvements in trabecular bone at the femur (Supplementary Fig. 10a–f). Similarly to the INK-ATTAC model, trabecular bone histomorphometry demonstrated lower osteoclast numbers per bone perimeter in D + Q–treated than in vehicle-treated mice (Supplementary Fig. 10g), and there were no differences in osteoblast numbers, mineral apposition rate, or boneformation rate (Supplementary Fig. 10h–j). Also similarly to the INK-ATTAC model, D + Q treatment resulted in higher femur cortical thickness and μFEA-derived bone strength (Fig. 2n–p). This was associated with lower osteoclast numbers on the endocortical surface (Fig. 2q), along with higher endocortical osteoblast numbers (Fig. 2r), mineral-apposition rate (Fig. 2s), and bone-formation rate (Fig. 2t). Thus, both the genetic (INK-ATTAC) and pharmacological (D + Q) approaches for clearing senescent cells led to virtually identical improvements in trabecular and cortical bone microarchitecture, demonstrating similar underlying cellular mechanisms in trabecular and cortical bone compartments.

 

 

[SearchingForAnswers]

What was the method of administration of the quercetin? I believe somebody here made a very convincing argument that oral quercetin was basically useless.

 

 

 

More promising results on the benefits of dasatinib as a senolytic, this time for reversing age-related bone loss.

 

“Targeting cellular senescence prevents age-related bone loss in mice” (2017) https://www.nature.c...ll/nm.4385.html

......."

 

[Nate-2004]

Tyrosine Kinase Inhibitors seem to break up beta amyloid plaques via autophagy. I do not know whether dasatinib is viable for this specific brain target because I'm not sure if it gets through the BBB.

[SearchingForAnswers]

 

What was the method of administration of the quercetin? I believe somebody here made a very convincing argument that oral quercetin was basically useless.

 

 

 

More promising results on the benefits of dasatinib as a senolytic, this time for reversing age-related bone loss.

 

“Targeting cellular senescence prevents age-related bone loss in mice” (2017) https://www.nature.c...ll/nm.4385.html

......."

 

 

 

Anybody?

[Ozone8]

As a new member who has read all 23 pages of this thread, please accept my thanks for all of the research, personal experimentation and thoughtful comments.

 

I do have a couple of questions:

 

- Is there a consensus on dosage and frequency of use for the D+Q regimen? Or perhaps a compilation of personal protocols? If so, where might these be located?

 

- Does anyone have a small quantity of dasatinib (2-3 gm) that they might be willing to part with? Or is there another reliable and legitimate source that can be recommended?

[bladedmind]

Hello, thanks to all for the work done on this topic.  I'm just like Ozone8, have read all pages, want to try the regimen.  I'm 68 and would gladly discard some senescence.   Advice on source for personal quantity is welcome.

[Rocket]

I bought mine from TLR but I think they are gone....

[Intelinc]

I recently purchased from TLR, and they seem to have stock. As originally requested by Ozone8, any semi-definitive redux of dosing/protocols for Dasatinib would be super-valuable on my end as well. 

[DareDevil]

A friend has recently started a protocol gradually increasing dosage. The fever symptoms seem to start at lower than 75mg/day. At 100mg/day they are bad enough you can't even think about going to work, so make sure you have a long weekend to recover. I don't know if there is a critical dose to reach for the senescent action to be at peak. Does one need to reach that feverish reaction point for it to be optimally effective? Or can one get results by longer dosage at lesser quantities? My only experience doing that was 2 weeks with 40mg/day of Sprycel, the prescription pharmaceutical version of Dasatinib - you don't want to know the price. If I remember it was around $3k for that run, fortunately it slid past my health insurance. I thought the price per pill was the price of the 30 pills at 20mg each, and I even found that to be expensive. 

 

I noticed enough positive benefits that I was eager to be in the Group Buy and I even jumped the gun by buying some from TLR before that went through. At 100mg/day it was nothing like the lower dosages, it became a brutally effective drug but it was brutal. I think one should keep dosage lower unless you weigh 300lbs. Also, there is a slightly delayed reaction of hollowing of facial fat that can leave you with a skeletal look. I had that happened and almost overnight looked 10 years older. People commented at how I'd lost fat where it hurts, and that I looked awful. That's not usually the sort of rejuvenating treatment we seek, so while it helps your health maybe, it doesn't show! So be very cautious in both dosage for its high fever, and in total intake for its effect on facial fat. Becoming gaunt isn't becoming if you're wishing to look younger.

 

Cheers,

 

DD

[Rocket]

A friend has recently started a protocol gradually increasing dosage. The fever symptoms seem to start at lower than 75mg/day. At 100mg/day they are bad enough you can't even think about going to work, so make sure you have a long weekend to recover. I don't know if there is a critical dose to reach for the senescent action to be at peak. Does one need to reach that feverish reaction point for it to be optimally effective? Or can one get results by longer dosage at lesser quantities? My only experience doing that was 2 weeks with 40mg/day of Sprycel, the prescription pharmaceutical version of Dasatinib - you don't want to know the price. If I remember it was around $3k for that run, fortunately it slid past my health insurance. I thought the price per pill was the price of the 30 pills at 20mg each, and I even found that to be expensive. 

 

I noticed enough positive benefits that I was eager to be in the Group Buy and I even jumped the gun by buying some from TLR before that went through. At 100mg/day it was nothing like the lower dosages, it became a brutally effective drug but it was brutal. I think one should keep dosage lower unless you weigh 300lbs. Also, there is a slightly delayed reaction of hollowing of facial fat that can leave you with a skeletal look. I had that happened and almost overnight looked 10 years older. People commented at how I'd lost fat where it hurts, and that I looked awful. That's not usually the sort of rejuvenating treatment we seek, so while it helps your health maybe, it doesn't show! So be very cautious in both dosage for its high fever, and in total intake for its effect on facial fat. Becoming gaunt isn't becoming if you're wishing to look younger.

 

Cheers,

 

DD

 

Dasatanib does not cause hollowing of the face.

 

I have probably ran a higher dose than anyone here and did not lose any body fat, and yes I got the fever and flu like symptoms. If anything I gained weight because of my diet and exercise routine.

 

Please don't say it causes your face to hollow out as if that is a fact. Only you know what else you are taking at the same time and what your diet is.
 

[roguereason]

Why is anyone talking about daily dose levels?  I thought the idea was to take one (maybe two) dose(s) every 6 months at the most.  Once you've killed enough senescent cells the drug is only doing harm.  I'm actually thinking of doing the 300mg dose, but only once. 

 

Hoping that that maximizes the benefits, but stops short of doing damage or giving me flu like symptoms.

 

I do have a few questions / thoughts though before I take the plunge.

 

I see that some people did 2 days instead of just 1, is there a reason for that?

 

I see from the original study how synergistic dasatinib is with quercetin when it comes to the HUVEC cells.  If I'm reading the graph right, the cells were cleared at half the level of Q. D alone does nothing to those.  This is good if raising Q levels is as hard as it seems.

 

But it looks to me like maybe Q is very slightly protective of the senescent preadipocyte cells that would have been killed by the D?  Although it is hard to read that much into the small printed graph.  Am I over analyzing that effect?  Still only half of those are destroyed.

 

I was actually thinking of doing D+Q first, and then a month later just D... to get more of those senescent preadipocytes... any thoughts on that?

 

Also I've seen many comments on here about how Quercetin is useless as far as bioavalibitlity in humans, but I've seen bits of studies of EMIQ that show that that does produce measurable Q levels in the blood.  Are those to be believed? Is there something I should know about the bioavalability of or form of quercetin in the blood after taking EMIQ?

My options:

 

D+(Q+Olive oil) -- this was my original plan before aquiring EMIQ.  Olive oil is supposed to improve absorption but people have brought up conversion in the liver.. so I'm not sure.

D+EMIQ 

D+EMIQ+(Q+Olive oil) - just in the hope that one of the two forms makes it to my blood stream

D+EMIQ+Fisetin - No idea if fisetin would be synergistic with its cousin Q, or with D. 

 

Then few weeks or a month later, a single dose of just D.  Get those remaining preadipocytes.

 

Also thinking of doing a topical application of D.  If nothing else it supposedly clears precancerous cells in mice.

 

Any thoughts?

[Skyguy2005]

 

What was the method of administration of the quercetin? I believe somebody here made a very convincing argument that oral quercetin was basically useless.

 

 

 

More promising results on the benefits of dasatinib as a senolytic, this time for reversing age-related bone loss.

 

“Targeting cellular senescence prevents age-related bone loss in mice” (2017) https://www.nature.c...ll/nm.4385.html

......."

 

 

Oral quercetin is not useless!
 

[Rocket]

Why is anyone talking about daily dose levels? I thought the idea was to take one (maybe two) dose(s) every 6 months at the most. Once you've killed enough senescent cells the drug is only doing harm. I'm actually thinking of doing the 300mg dose, but only once.

Hoping that that maximizes the benefits, but stops short of doing damage or giving me flu like symptoms.

I do have a few questions / thoughts though before I take the plunge.

I see that some people did 2 days instead of just 1, is there a reason for that?

I see from the original study how synergistic dasatinib is with quercetin when it comes to the HUVEC cells. If I'm reading the graph right, the cells were cleared at half the level of Q. D alone does nothing to those. This is good if raising Q levels is as hard as it seems.

But it looks to me like maybe Q is very slightly protective of the senescent preadipocyte cells that would have been killed by the D? Although it is hard to read that much into the small printed graph. Am I over analyzing that effect? Still only half of those are destroyed.

I was actually thinking of doing D+Q first, and then a month later just D... to get more of those senescent preadipocytes... any thoughts on that?

Also I've seen many comments on here about how Quercetin is useless as far as bioavalibitlity in humans, but I've seen bits of studies of EMIQ that show that that does produce measurable Q levels in the blood. Are those to be believed? Is there something I should know about the bioavalability of or form of quercetin in the blood after taking EMIQ?

My options:

D+(Q+Olive oil) -- this was my original plan before aquiring EMIQ. Olive oil is supposed to improve absorption but people have brought up conversion in the liver.. so I'm not sure.
D+EMIQ
D+EMIQ+(Q+Olive oil) - just in the hope that one of the two forms makes it to my blood stream
D+EMIQ+Fisetin - No idea if fisetin would be synergistic with its cousin Q, or with D.

Then few weeks or a month later, a single dose of just D. Get those remaining preadipocytes.

Also thinking of doing a topical application of D. If nothing else it supposedly clears precancerous cells in mice.

Any thoughts?

One big dose is exactly what I did. The idea of continually running a cancer drug is pretty insane. I think people want to take these tiny daily doses to avoid side effects.... But there are no studies pointing to evidence that small daily doses will do anything. The mouse study was one big dose, which is how I run it. Just my $0 .02.

[Ozone8]

But wasn't the equivalent mouse to human dosage from the study around 30 mg for a 70 kg person? Thought I read that calculation in past pages. If so, you took 10 times that amount in the 300 mg dose.

 

I agree that it should be taken very infrequently.

 

 

[Alpharius]

Quercetin in phytosome (phosphatidylcholine) is much better orally available then quercetine alone. Lipid carriers enhance the quercetin uptake up to 6-fold. 

https://www.ncbi.nlm...pubmed/27756627

https://www.ncbi.nlm...pubmed/23514412