731 replies to this topic

[jmorris]

Ha!. I said viscous cycle. 

 

If anyone is interesting in learning more about upadacitinib specifically there is a draft wikipedia article waiting to be approved.

(Disclosure: I am its author.)

Edited by jmorris, 25 May 2017 - 07:13 AM.

[Andey]

Well, this topic died a sudden death.

 

  Should we move to another target for group buy then ? )

FOXO4-DRI looks promising.

Few folks tried it already http://foxo4dri.com/day-25/ and http://www.longecity...ndpost&p=816864 and it seems safe and promising.

Expensive though, but if could get it down to $100 for 10mg I would buy it. 30 mg or 5mg +30 mg could do a trick.

 

 

 

Edited by Andey, 25 May 2017 - 07:17 AM.

[jmorris]

 

Well, this topic died a sudden death.

 

  Should we move to another target for group buy then ? )

FOXO4-DRI looks promising.

Few folks tried it already http://foxo4dri.com/day-25/ and http://www.longecity...ndpost&p=816864 and it seems safe and promising.

Expensive though, but if could get it down to $100 for 10mg I would buy it. 30 mg or 5mg +30 mg could do a trick.

 

 

See my thoughts two posts above for thoughts regarding a next step using a JAK1 inhibitor that you might have missed. I also detail the current cost of synthesizing FOXO-DRI from peptide synthesis companies. (I do agree that FOXO-DRI is an exciting compound.)

Edited by jmorris, 25 May 2017 - 07:25 AM.

[Andey]

 

 

Well, this topic died a sudden death.

 

  Should we move to another target for group buy then ? )

FOXO4-DRI looks promising.

Few folks tried it already http://foxo4dri.com/day-25/ and http://www.longecity...ndpost&p=816864 and it seems safe and promising.

Expensive though, but if could get it down to $100 for 10mg I would buy it. 30 mg or 5mg +30 mg could do a trick.

 

 

See my thoughts two posts above for thoughts regarding a next step using a JAK1 inhibitor that you might have missed. I also detail the current cost of synthesizing FOXO-DRI from peptide synthesis companies. (I do agree that FOXO-DRI is an exciting compound.)

 

 Yep, I ve missed it.  Thanks for heads up )

I even read about JAK1 inhibition and senescence before.  It should be pretty safe short term as the main thing it will do is shut down cytokine production (it could be even beneficial), and a not so good in a long term.

Why do you think in terms of year supply terms though ? My take on senolitics is as it could and should be taken in a larger dose but only once or two per year. No need to overstress body with constant exposure to them. It will have some positive effect but I imagine quite marginal and safety and cost would not be good at all. And I treat safety as paramaunt here.

Edited by Andey, 25 May 2017 - 07:57 AM.

[jmorris]

Why you think in terms of year supply terms though ? My take on senolitics is as it could and should be taken in a larger dose but only once or two per year. No need to overstress body with constant exposure to them. It will have some positive effect but I imagine quite marginal and safety and cost would not be good at all. And I treat safety as paramaunt here.

 

Good question. 

 

JAK1 inhibitors are senotherapeutics (silencing senescent cells) rather than senolytics (which kill sensescent cells) so they would need to be taken every day.

 

Like I mention in my post, such a drug would not only need to be inexpensive and potent but also would have to meet very high safety standards to be considered a daily treatment. It is my belief that filgotinib and upadacitinib satisfy such standards due to them having pass with flying colors to phase III trials.

 

Remember it is my vast preference to go the route of senolytic rather than senotherapeutic but I just don't see a viable route to an affordable senolytic right now so there is a need to compromise. One thing I am not going to compromise on is I have to so something, not nothing, and I want to do it as fast as possible. I consider this a race. The prize for losing is suffering and death, a taste of which I experience daily.

 

One more thought about FOXO-DRI before I accidentally change the subject from JAK1 after spending days writing a long post on it. (Again, please see above):

 

When one wants to try an experimental drug and be anywhere close to responsible (kind of a contradiction, I know) you need at least one thing:

 

1) The half life of the compound in humans.

Without this, you might be taking the drug regularly and have it start to build up in your system. If it gets to a toxic dose you will be screwed waiting for it to get out of your system. Time for dialysis if it's not too late! Or, you might be spending lots of money and pissing it all out. We don't have this information in humans for FOXO-4.

 

It would also be very nice to have...

 

2) The bioavailability.

Without this, we don't know the relationship between how much we are taking and what the amount will be in our cells.

 

We can get around this by going intravenous but I would rather not.

 

Ideally, I would also want to know...

 

3) The ED50.

 

We don't know any of these things.

 

The guy at the site you cite above is somehow calculating dosage from a scaling factor based on skin area. Let me tell you that this is child-like in its naivete. The only people who use skin area to calculate dosage are oncologists for chemo and even many of them think it is useless.

 

See: 

Body-Surface Area–Based Chemotherapy Dosing: Appropriate in the 21st Century?

http://ascopubs.org/...co.2012.44.2863

 

I also read various posts on this site trying to hand-wave ways to convert from rodent to human dosages. They are similarly naive since this completely disregards the interspecies differences in the liver and kidneys. Pretty important.

 

We have no idea what the dosage should be in humans or anything about the safety of this drug. Bottom line is that FOXO-DRI is very exciting. But it is also very, very young. Trust me, I share your excitement.  I'm sure they are planning human studies. It won't be long. Then you are going to have to solve the cost problem, which I have detailed a few posts above.

[Andey]

 

Why you think in terms of year supply terms though ? My take on senolitics is as it could and should be taken in a larger dose but only once or two per year. No need to overstress body with constant exposure to them. It will have some positive effect but I imagine quite marginal and safety and cost would not be good at all. And I treat safety as paramaunt here.

 

Good question. 

 

JAK1 inhibitors are senotherapeutics (silencing senescent cells) rather than senolytics (which kill sensescent cells) so they would need to be taken every day.

 

Like I mention in my post, such a drug would not only need to be inexpensive and potent but also would have to meet very high safety standards to be considered a daily treatment. It is my belief that filgotinib and upadacitinib satisfy such standards due to them having pass with flying colors to phase III trials.

 

 

 Sorry I missed that its a senotherapeutics. Looks like it similar in that regard to fasting as it also have some prolonged silencing effect on senescent cells.

Its clear that I need to read your post above with full attention it deserves, and I will. ) It was just quick cowboy style answer while I am at work. 

[jmorris]

ATTENTION: To all readers of this forum who have participated in the Dasatinib group buy.

 

Expectations are funny things. They can turn something good happening into something bad. Or they can turn something bad happening into something good. I've heard a lot of disparaging comments about dasatinib "not doing anything" and I wanted to give you my thoughts on the matter. 

 

What, exactly, was your expectation when taking dasatinib? From reading the recent comments this is what I imagine:

 

Day 1: Take dasatinib. Experience some limited side effects. Must be all those senescent cells dying, huh?

 

Day 2: Feel fine.

 

Day 3: More energy. Skin is looking better. Wrinkles are disappearing.

 

Day 4: I ran 10 kilometers today like it was nothing and in the evening I had the best sex of my life.

 

Day 5: Hair has almost completely grown back and it is now the color when I was in school. Wrinkles completely gone.

 

Day 6: I am now stronger than most mortal men. During my lunch break I stopped a robbery by catching the bullet in my teeth. On my way home I rescued a family from a flaming car accident by lifting the car with one hand.

 

If you have this ridiculous expectation then yeah, Dasatinib did nothing at all. What a waste of time, huh? Might as well chuck it.

 

To those of you expecting results of your skin looking better, your hair thickening up and then feeling like a million bucks a week later, I have news for you: That's not possible. That's not the way the biology works out.

 

Okay, but what is reasonable?

 

As far as we know, dasatinib only affects senescent fat cell progenitors. That's actually great news. If I had to pick a single organ I would most like to drain of senescent cells, adipose tissue is pretty near the top of the list. It's known to be not only be an energy storage depot but it's also a very important endocrine organ. What's more, it's dysfunction is implicated in many diseases of aging. For many of us, it is the largest organ in our bodies.

 

From:

Tchkonia, T., Morbeck, D.E., von Zglinicki, T., van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M.D., and Kirkland, J.L. (2010). Fat tissue, aging, and cellular senescence. Aging Cell 9, 667–684.

 

"Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mutations affecting fat increase life span. Fat cells turn over throughout the life span. Fat cell progenitors, preadipocytes, are abundant, closely related to macrophages, and dysdifferentiate in old age, switching into a pro-inflammatory, tissue-remodeling, senescent-like state. Other mesenchymal progenitors also can acquire a pro-inflammatory, adipocyte-like phenotype with aging. We propose a hypothetical model in which cellular stress and preadipocyte overutilization with aging induce cellular senescence, leading to impaired adipogenesis, failure to sequester lipotoxic fatty acids, inflammatory cytokine and chemokine generation, and innate and adaptive immune response activation. These pro-inflammatory processes may amplify each other and have systemic consequences. This model is consistent with recent concepts about cellular senescence as a stress-responsive, adaptive phenotype that develops through multiple stages, including major metabolic and secretory readjustments, which can spread from cell to cell and can occur at any point during life. Senescence could be an alternative cell fate that develops in response to injury or metabolic dysfunction and might occur in nondividing as well as dividing cells. Consistent with this, a senescent-like state can develop in preadipocytes and fat cells from young obese individuals. Senescent, pro-inflammatory cells in fat could have profound clinical consequences because of the large size of the fat organ and its central metabolic role."

 

The positive effects of taking dastinib would most likely be the lack of bad things happening, not suddenly feeling like you are 21 again only two days later.

 

If you can read that and not be excited about having access to dasatinib, I don't know what else to tell you.

 

Logic has done us the great service of organizing a group buy for dasatinib at a very good price. If you are disappointed that it didn't do anything then you need get some reasonable expectations.

 

I am very happy with my purchase and if given the chance to buy dastinib again, I might do so. It is a cutting edge tool and an amazing fact that we have access to it.

 

My advice: Barring side effects, take your dasatinib no more than a couple of days at a time and then only do this no more than a few times per year. Heck, maybe only once per year would do it. Who knows? Be happy you have this tool that 99.999999% of humanity does not.

 

(Also please check out my JAK1 group buy post above. I would love to hear some comments about it.  )

[niner]

Also, do we even know with assurance that this white powder that showed up is indeed dasatinib? We wouldn't be the first suckers in the history of the world.

Just for the record, Logic has some experience with the lab that provided the Dasatinib, and we think that they are reasonably good.  However, being the distrustful sorts that we are, we sent it to an analytical lab here in the US, where it was checked for purity via HPLC and for identity via Mass Spec.  The HPLC result tells us that it is a single compound of high purity (or multiple compounds that co-elute, rare but not impossible).   The MS result told us that it was the correct molecular weight and isotopic ratio for Dasatinib.  While this is far from the sort of structural characterization that you'd need for an FDA submission, it's a hell of a lot better than the usual Research Chemicals, Supplements, and random bags of powder that we happily consume.

[sthira]

Also, do we even know with assurance that this white powder that showed up is indeed dasatinib? We wouldn't be the first suckers in the history of the world.

Just for the record, Logic has some experience with the lab that provided the Dasatinib, and we think that they are reasonably good. However, being the distrustful sorts that we are, we sent it to an analytical lab here in the US, where it was checked for purity via HPLC and for identity via Mass Spec. The HPLC result tells us that it is a single compound of high purity (or multiple compounds that co-elute, rare but not impossible). The MS result told us that it was the correct molecular weight and isotopic ratio for Dasatinib. While this is far from the sort of structural characterization that you'd need for an FDA submission, it's a hell of a lot better than the usual Research Chemicals, Supplements, and random bags of powder that we happily consume.

Thanks for that. Gives me more confidence.

Hey, what's been your experience with your DQ experimentation? Care to share it?

[Andey]

 

(Also please check out my JAK1 group buy post above. I would love to hear some comments about it.  )

 

  I have my own objections for JAK inhibitors. Looks like JAK1 interfere with IL2, IL4, IL6, ... cytokines. I havent seen study that shows exactly net effect from JAK1 inhibition, as majority of agents are cross inhibing few JAKs but all of them have immunosuppresive effect. That is easy to see at ruxolitinib manual as risk of severe infection is a major side effect.  

  I suspect that short term its okay, even beneficial, you could treat it as a cryotherapy session which also shutdowns cytokines for some time. Long term it could lead to activation of all chronic persistent infections agents. Its no fun, I could say it from own experience as former Lyme disease patient. Especially in advanced age when persons own specific/adaptive immune system is already suppressed to some degree.  

Edited by Andey, 26 May 2017 - 08:19 AM.

[DareDevil]

Hi Friends,

 

I don't want to be the one who discourages others from experimenting with Dasatinib. Please note that my issues were NOT with this substance taken at normal recommended doses. They were caused by my abuse of dosage.

 

Over a course of a short period of a few weeks, I absorbed close to a total of 3 grams of Dasatinib. This is considerably greater than what is recommended in order to kill senescent cells without killing off healthy cells. It is therefore likely that my excessive dosing caused me to lose healthy fat cells that this drug would not have targeted at lower doses. Therefore my issues should not be taken as an example of what normal intake of D causes, but only what overdosing on D might bring.

 

Also, I am at the age where fatty tissues are leaving the orbital area of the face and migrating downwards. This means that I was already more aesthetically vulnerable to any decrease in facial fat than most people would be. Accentuating a hollow can make you look much worse even if very little fat is removed from a limited presence of facial fat. The distance between little to none is small, making it important to not abuse dosage of Dasatinib if you've already lost plumpness in your face.

 

The however leaves intact the claims made of Dasatinib effectively cleansing the body of senescent cells. We cannot discount this happening just because one member was excessive in dosing when already at cosmetic risk of looking older. While I look forward to other senolytic drugs, I am happy to have Dasatinib and will take it again, at much lower total intake.

 

Also, I wanted to point you guys to something else I recently tried, in order to boost my stem cells prior to having stem cell injections. It is called Zoledronic acid. I don't recommend anyone else taking it, but thought some of you would have ideas about its active principles and potential.

 

http://www.longecity...oledronic-acid/

 

Cheers,

 

DareDevil

[Fafner55]

Topical Dasatinib Treatment to Improve Skin

Topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse. It might be effective in improving skin in humans.

1. “Old Concept, New Drug: Topical Application of Systemic Antineoplastic Agent to Treat Skin Cancer” http://www.mdedge.co...ation-systemic 
2. “Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell–cell adhesion” (2014) http://onlinelibrary....22190/abstract

 

Since 120 mg dasatinib taken orally resulted in minor sloughing of my skin ( the bulk of sun damaged skin remains) I can assume that 120 mg / body weight is a minimum starting dose for topical treatment.

 

Ratioing 120 mg / 70 kg body weight to the approximate weight of my skin (8.8 kg) gives 15.1 mg dasatinib for my entire skin. 

 

I found that 1 tbsp (15 gm) of body lotion is needed to cover my entire body. That amount, mixed with 15 mg Dasatinib is my starting point. 

 

Building on other experience, I ground and added 400 mg honokiol. Unlike many other polyphenols, honokiol is white and does not stain, making it a good candidate for increasing the effects of dasatinib.

 

For the base I used either Cerave lotion or DMSO 70%.

• Cerave lotion is well absorbed by the skin and does not feel greasy. 
• DMSO 70% penetrates better than lotion and can be applied to lips and hair.

 

After much experimentation I found this mixture to potently treat sun damaged skin. It is best to start slowly, such as

• Apply once then wait a few days. Skin will redden and will improve without peeling. One application will visibly improve sun damaged skin.
• After several rounds of single application treatments, increase the dose to two applications an hour or so apart, letting the first application be fully absorbed. Wait a few days or do this once/week. 
• Skin with severe sun damage, such as the back of hands, might need three applications in a day. Do this once and wait two weeks. Three applications to the face will cause minor peeling that can persist two weeks or longer.
• Do not apply 4 applications in a day. That dose has the effect of a medium depth chemical peel, such as with TCA. Going slower is safer and effective.

 

This mixture is potent and dangerous. Three applications / day for five successive days resulted in tingling and numbness on my face.  Fortunately, the nerves were stunned, not killed, and feeling returned to normal in about a week. Neuropathy is a possible side effect of dasatinib.

 

The improvement to my skin has been remarkable. Small keratoses have disappeared (some larger ones receded but remain), skin roughness improved, hyperpigmented spots receded or disappeared, loose skin on my neck tightened and fine wrinkles are much reduced. Overall, the appearance of skin on my face and neck improved by at least 15 years.

 

I plan to continue with one application/week for the next couple of months.

[Nate-2004]

Why would this work?

[Fafner55]

This treatment works by pushing harder on the BAX/BCL ratio to induce apoptosis in DNA damaged cells.

[Andey]

 

Topical Dasatinib Treatment to Improve Skin

 

 

  Wow, thats interesting ) Thanks !

[stefan_001]

This treatment works by pushing harder on the BAX/BCL ratio to induce apoptosis in DNA damaged cells.

 

Interesting indeed, thanks for reporting. You mentioned skin tightness, I recall you track the skin elasticity on..was it your arm, did that improve as well?

[Nate-2004]

This treatment works by pushing harder on the BAX/BCL ratio to induce apoptosis in DNA damaged cells.

 

Pretty sure my skin wouldn't benefit much from this, it's lacking the collagen, fat and bone support I had in my 20's, I doubt it would give that back. I have been trying the breast enlargement formula for a couple of weeks now, twice a day, and I haven't seen any results as of yet. 

Edited by Nate-2004, 31 May 2017 - 01:12 PM.

[Longevitarian]

Hi Fafner55'

 

Very interesting.

I am curious which D purchase version did you use for your skin rejuvenation experiment?

[Longevitarian]

Hi jmorris'

 

You have flooded us with deluge of ideas lately, each of which would require separate board to cover.

I am on the same wavelength as you with all your postings, especially those concerning the Navitoclax,

Jak/Stat inhibitors , FOXO4-DRI, And the controversies and undue criticisms of some malinformed

individuals regarding Dasatinib.

Keep doing a good job.

[Fafner55]

 

This treatment works by pushing harder on the BAX/BCL ratio to induce apoptosis in DNA damaged cells.

 

Interesting indeed, thanks for reporting. You mentioned skin tightness, I recall you track the skin elasticity on..was it your arm, did that improve as well?

 

 

The crepe-like appearance of skin on the inside of my forearms is improved, but traces of it still persist.

 

Skin tightness is something I monitor on my neck. When bending over a mirror with my head tilted down, loose skin at the base of my neck above the chest would hang about 1 cm. Now, after these treatments no skin hangs down. That is not to say that my neck skin is as taut as a teenager's, but there has been significant improvement.

 

I don't have reason to attribute this improvement to direct up-regulation of type 1 collagen COL1A1 gene expression. Evidence is that the areas of my skin that are not exposed to the sun are not wrinkled or loose, so those problems are associated with solar damaged cells. Removing those cells then lead to improvements.

 

It could be that inflammatory transcription factors such as NF-kB which inhibit collagen production are reduced, and there must be other factors.

1. “NF-kappaB inhibits expression of the alpha1(I) collagen gene” (1999) https://drive.google.com/open?id=0B_pfWfFEQDILdnlrQWNXQ252Nlk
2. “Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading” (2004) http://physrev.physiology.org/content/84/2/649

[Nate-2004]

Honokiol is the only substance I recognize on a long list of substances that can inhibit NF-kB is that why you used that?

[Fafner55]

This treatment works by pushing harder on the BAX/BCL ratio to induce apoptosis in DNA damaged cells.

 

For support, 

 

Dasatinib potently inhibits BCL-2 (anti-apoptotic) and induces BAX (pro-apoptotic).

1. “The Achilles' heel of senescent cells: from transcriptome to senolytic drugs” (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531078/
2. "Philadelphia chromosome"), Src, c-Kit, ephrin receptors, and several other tyrosine kinases.  “Targeting BCL-2 and ABL/LYN in Philadelphia chromosome–positive acute lymphoblastic leukemia” (2016) http://stm.sciencemag.org/content/8/354/354ra114.full   
3. “Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage” (2015) https://www.spandidos-publications.com/ijo/47/3/1103

 

Honokiol potently inhibits BCL-XL (anti-apoptotic).

1. “Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells” (2002) https://drive.google.com/open?id=0B_pfWfFEQDILeUw1NHBsQXV5LUU

 

A good pictorial overview of the relationship between apoptosis effectors is shown in Figure 1A of “Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging” (2017) http://www.cell.com/cell/fulltext/S0092-8674(17)30246-5

 

 

Modulating the BAX/BCL ratio has long been a target for inducing apoptosis.

1. “Tocotrienol-rich fraction of palm oil activates p53, modulates Bax/Bcl2 ratio and induces apoptosis independent of cell cycle association” (2004) https://www.ncbi.nlm.nih.gov/pubmed/14712090

[Fafner55]

Honokiol is the only substance I recognize on a long list of substances that can inhibit NF-kB is that why you used that?

 

I used honokiol to kill cells that can produce NF-kB transcription factors, not to inhibit NF-kB.

[Andey]

I used honokiol to kill cells that can produce NF-kB transcription factors, not to inhibit NF-kB.

 

 

  Have you tried dasatinib or honokiol separately with the same topical administration method ? I imagine Honokiol could work by itself and dasatinib is just a dead weight...or vice versa.

It would be interesting to include fisetin to this cocktail as it apparently also have some transdermal penetration. https://www.ncbi.nlm...les/PMC4294956/

[Fafner55]

 

I used honokiol to kill cells that can produce NF-kB transcription factors, not to inhibit NF-kB.

 

 

  Have you tried dasatinib or honokiol separately with the same topical administration method ? I imagine Honokiol could work by itself and dasatinib is just a dead weight...or vice versa.

It would be interesting to include fisetin to this cocktail as it apparently also have some transdermal penetration. https://www.ncbi.nlm...les/PMC4294956/

 

 

I did not try honokiol and D as separate topical treatments. I did try them separately when experimenting with oral treatments and found the combination to be more effective, so I continued with the combination for topical treatments.

 

While fisetin induces apoptosis and would make the mixture more potent, it like many polyphenols is a coloring agent that will stain skin.

[shadowhawk]

 

Topical Dasatinib Treatment to Improve Skin

Topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse. It might be effective in improving skin in humans.

1. “Old Concept, New Drug: Topical Application of Systemic Antineoplastic Agent to Treat Skin Cancer” http://www.mdedge.co...ation-systemic 
2. “Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell–cell adhesion” (2014) http://onlinelibrary....22190/abstract

 

Since 120 mg dasatinib taken orally resulted in minor sloughing of my skin ( the bulk of sun damaged skin remains) I can assume that 120 mg / body weight is a minimum starting dose for topical treatment.

 

Ratioing 120 mg / 70 kg body weight to the approximate weight of my skin (8.8 kg) gives 15.1 mg dasatinib for my entire skin. 

 

I found that 1 tbsp (15 gm) of body lotion is needed to cover my entire body. That amount, mixed with 15 mg Dasatinib is my starting point. 

 

Building on other experience, I ground and added 400 mg honokiol. Unlike many other polyphenols, honokiol is white and does not stain, making it a good candidate for increasing the effects of dasatinib.

 

For the base I used either Cerave lotion or DMSO 70%.

• Cerave lotion is well absorbed by the skin and does not feel greasy. 
• DMSO 70% penetrates better than lotion and can be applied to lips and hair.

 

After much experimentation I found this mixture to potently treat sun damaged skin. It is best to start slowly, such as

• Apply once then wait a few days. Skin will redden and will improve without peeling. One application will visibly improve sun damaged skin.
• After several rounds of single application treatments, increase the dose to two applications an hour or so apart, letting the first application be fully absorbed. Wait a few days or do this once/week. 
• Skin with severe sun damage, such as the back of hands, might need three applications in a day. Do this once and wait two weeks. Three applications to the face will cause minor peeling that can persist two weeks or longer.
• Do not apply 4 applications in a day. That dose has the effect of a medium depth chemical peel, such as with TCA. Going slower is safer and effective.

 

This mixture is potent and dangerous. Three applications / day for five successive days resulted in tingling and numbness on my face.  Fortunately, the nerves were stunned, not killed, and feeling returned to normal in about a week. Neuropathy is a possible side effect of dasatinib.

 

The improvement to my skin has been remarkable. Small keratoses have disappeared (some larger ones receded but remain), skin roughness improved, hyperpigmented spots receded or disappeared, loose skin on my neck tightened and fine wrinkles are much reduced. Overall, the appearance of skin on my face and neck improved by at least 15 years.

 

I plan to continue with one application/week for the next couple of months.

 

I have had much the same remarkable results from taking quercetin from RevGenetics, six pumps a day.  My skin looks 20 years younger.  All over my body blemishes fell off.  A few sun damaged blemishes remain.  This has remained now for over six months.  My family can hardly believe it.  I did apply it topically a few times with good results.

[njurkovi]

At 6 pumps a day that is pretty expensive. How many days till you saw the results?

[shadowhawk]

I started seeing noticeable results a little over a week.  My skin is now clear and smooth except for a couple  of sun damaged spots on my forehead.  A pump lasts about one month.

[meatsauce]

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.

[tintinet]

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!