Senolytics

Charles Grashow The dasatanib was compounded by TMC http://ww.tailormadecompounding.com/

6 50mg capsules were approximately $30. 

The quercetin 250 mg capsules were purchased on Amazon. The supplier was Pure Encapsulations. $21.70 for 60 capsules. 

Sam Biller These folks require a prescription but will send you a list of clinics in your area that may be able to assist with that.  We'll see 2what happens.

Sam Biller I had a remarkably better balance on a yes4all board after taking D&Q. Try it, very unexpected. 

Larry Interesting on the improved balance. 

Here are my blood test results received earlier today. The change in some of these numbers is probably more related to my recent change to a ketogenic diet versus the pharmaceutical additions. 

Sam Biller I just tried to call them up and they refused to give me a price unless I get a prescription and then they will only give the doctor a price... wierd.... are you sure on the price? It seems rather low....

garland I've communicated with them directly and set up a physicians account for my practice. The price quoted to me was $3.50 for each 50mg capsule of dastinib. They also fill prescriptions for rapamycin at $3.00 for a 3mg capsule. They are a pharmacy and require a prescription which they recieve by fax directly from physicians office. I plan to begin using them for patients and personal.

Mark Thimineur Thanks so much..... are you a doctor that specializes in Anti Aging stuff? Sounds like it. Where are you out of? Do you do phone apts? You sound like an incredible resource. I was using the pharmacy in Florida where the pharmacist recently passed away. SO alot of us are in the same boat with no source for Dasatinib

garland Interventional pain management specialist who has integrated several anti-aging treatments into the long term treatment plans for a growing number of my older chronic pain patients with notable effects on disease and pain. I also personally treat some non-chronic pain patients - namely myself, my family, and some close associates and friends. I may set up a limited anti-aging practice because I see the need but I am very busy with my current practice. If or when I do this I will make it known. Right now I'm just in a stage of thinking about the mechanisms and structure that will allow a legit doctor patient relationship with proper follow up and monitoring. My location is Connecticut

Mark Thimineur 

FYI, I emailed Taylor made compound pharmacy and they did respond with a price that comes out to two dollars per milligram available in 3 mg tablets and my dr  is required to set up an account.

So maybe prices are going up?

Mark Thimineur I have been wondering if rapamycin could be beneficial for my 30-year-old daughter immune system as she  is constantly getting sick with colds? She has been chronically sick for the last 10 years and has had Graves’ disease, is on cortisol 35 mg a day as her adrenals do not work and she was  recently diagnosed  with Lyme disease which we think is the cause of all these problems, (that we think she contracted in high school.) She does a lot of alternative therapies including nutritional IV‘s, hyperbaric oxygen and has had exsomes injections which the doctor hoped would possibly benefit her inflamed biceps, in addition to the lymes.

I don’t see a downside to experimenting with it other than it possibly impacting her digestion which  is a daily problem part of which is related to fighting colds and having her gallbladder removed.

In your experience with rapamycin have you observed  a benefit for the immune system and how often does it affect digestion?
We are desperate to try to improve the quality of her life as she never has a normal day and if she wasn’t constantly fighting colds that would be A big help. 
Thank you in advance for your observations!
 

John Mcgough The combination of Graves dz, Addisons dz, diffuse pain, gut symptoms, frequent "sickness" may be related (polyglandular autoimmune syndrome(s) or other related disorders). I assume there has been some eval on this and perhaps no clear answer. Seems like a coexistence of variable autoimmune and immunodeficiency. This is complicated and I have no clear answer for you in regards to mtor inhibitory treatments.

General observations and known effects of mtor complex 1 inhibition is to improve immune function among older individuals. People treated with anti-aging rapa dosing seem to report less illness or shorter recovery.

Rapa treatment in rodents and flies, and presumably all animals and humans will change gut microbiome from the mouth through to the colon. This has generally been considered benevolent or has improved health (periodontal disease improvement) and resulted in less measurable stool produced in rodent studies. People seem to observe they poop less.

The youngest person I have treated is 30. This was due to a very stubborn rectal pain syndrome which was evaluated by multiple specialists without a clear etiology and required my prescription of clonezepam to suppress somewhat. At 3mg per week in this 62 kg person (over 6 months) there was reduction in pain and reduction in ADHD and anxiety, both of which were lifetime significant disorders. I have monitored this young person closely - no signs of anything adverse.

I can't point to any specific personal observation or scientific study which would contraindicate a trial of rapa. I cannot provide specific medical advise other than that. Effects on your daughters condition would be of interest.

Mark Thimineur thank you for your response. Are there any specific  test or special clinics or great Drs.  that you know of you that you recommend to check out  and treat polyglandular autoimmune syndrome? What type of doctor  specialize in this? I have googled APS-1 and it certainly seems to fit my daughter as an addition to the above problems I mention she has been on bio-identical hormones for years. It sounds like the treatment is to manage each problem as it occurs which is what we have done.

 The only other reason I can think of not to try rapamycin is that Lyme is from a bacterium and Dr. Green states you are at risk of bacteria infections with rapamycin. So do you think this could make the Lyme  disease worse because of the higher risk of bacteria infections or is it unrelated and not a risk factor?

Her weight is about 145 pounds similar to the person you mentioned so you would recommend a 3 mg dose?

thank you for your help and it seems like you have identified the exact problem.

John Mcgough Antibiotic eliminates the tick borne borrelia burgdorferi spirochete completely. If treated, there is no infection. Chronic lyme symptoms occur in rare patients. However, these occur despite bacterial clearance and represent a baffling array of symptoms of unclear cause(s). What we know is there are no "lyme bacteria" in the body after treatment and none in the chronic symptom sufferers. That said, if she has had treatment, there cannot be worsening of Lyme with rapa. 

To my knowledge, treatment for APS syndromes is hormone replacements. Probably the specialists with the most knowledge are endocrinologists but the treatment is simply to replace the deficient hormone. No preventatives that I know of.

3mg dose (0.05mg/kg)  in a 30 year old make sense. consider maxing at 4mg (0.067mg/kg). Ages 45 and older usually means higher dosing between 0.08mg/kg to 0.15mg/kg per week. This has been my approach. Much of that is empiric and I think follows Blogsklonney and Alan Green parameters.

Mark Thimineur 

Thank you for your enlightening response. 
At this point I think we should retest since she never underwent antibiotics treatment  because the doctor thought the side effects would be too rough on her fragile system so he used natural medicine products that she could start in small doses and slowly increase in an attempt to kill it. 

If it is in-fact killed then we will try rapa. Thanks again.

John Mcgough 

John Mcgough Hello, John. I would start on LDN before I did anything else. LDN has accomplished miracles in the field of autoimmune diseases. It is a modulator of the immune system. And even seems to work with Lyme as well as other most other immune system diseases. Wishing you well. In your search

garland 

thank you for your suggestion and I appreciate input from anyone with  information. She has been on LDN starting  right after she had Graves’ disease about 10 years ago and it helped lower her antibodies from 1200 to below 50over many years.

it’s only after many years of struggle, having to go on by identical hormones, and her having Addison’s disease two years ago that one doctor tested for Lyme disease last summer which came up positive. At that point we recalled A high school camping trip in which we think she contracted Lyme  disease.

now she is often sick with a cold and I was thinking of trying rapamycin  as there are Studies that show it helps the immune system. But the problem is we don’t want the Lyme  disease to get worse if it has not been fully killed since she never took antibiotics as the doctor thought she couldn’t handle them and only took Chinese herbslike cat claw, skullcap and garlic which she could start in small doses and gradually increase. Currently she is off them as she is taking Candida medicine and plans to go back on them after the  candida is eliminated.

and again thank you for your suggestion.

John Mcgough I've now set up a practice account with Tailor and trying to master their EMR. Created and sent first patient script for rapamycin 3mg capsules. Total invoice for a 3 month supply of 6mg per week is $68.40 which comes out to $0.95 per milligram. There may be an additional charge for shipping. It may be that a script billed to practice account is discounted. Not sure.

Mark Thimineur hello again... I bought 5 bottles of the Sirolimus transdermal Cream with the idea of mixing a capsule of the Sirolimus with the cream but the bottles are not easy to break apart.  Once we get it apart where do you store the material after you have mixed in some of the Sirolimus? I assume that you first mix the new Sirolimus with the DMSO etc and then add it to the one prepared from Tailor Made? I assume that you found that the higher concentration of Transdermal Sirolimus gives better results then the one from Tailor Made? I know you use DMSO as one of the new ingredients to mix with...what are the other ones you mix it with? How much does a one mg amount of Siromilus integrated into one of those bottles create? Are we close to the amounts that you use in your batches? Any ideas would be greatly appreciated....thanks

garland The Tailor Made topical is .001% which is .01mg sirolimus per gram of the cream. I believe the Tailor Made topical is sold in 30 gram containers (of some sort). The total milligrams of Sirolimus in the 30 gram containers at .001% concentration is 0.3mg. I prefer to express in molar concentrations so that is just about 11 micromolar. I have mixed my topical at 25 micromolar and have found it to be extremely effective.

To make this concentration using the topical you have purchased you would add 0.68mg of sirolimus to each 30 gram container. That is impossible doing this at home. Rather, if you combined all of the sirolimus topical you have purchased together getting 150grams, you would need to add 3.4mg sirolimus to get 25 micromolar. Since there is bound to be some wastage, adding 3mg would also get around this concentration.

In essence, add 3mg sirolimus to all of your purchased topical.

It would be much less expensive if you simply make your own. First purchase Dimethyl sulfoxide liquid (3.4 Oz - 100ml), Pharmaceutical grade, High purity, Heiltropfen from Amazon for $13.70. Then purchase DMSO Cream With Aloe Vera - Lavender Scented, Made With 99.9% Pure Pharmaceutical grade DMSO - 70% DMSO/30% Aloe Vera, Made in USA for Live Better Naturals 4 oz from Amazon for $19.87.

Take 3mg of sirolimus - if from capsule it is already powder, if from tablet you have to use mortar and pestle. Mix that with 3-4 ml of DMSO. I suggest using a small capped test tube or something that can be shaken vigorously and allowed to sit for 10 minutes so all the sirolimus is dissolved. The fillers in the capsule or tablets won't dissolve completely so the solution will be cloudy.

Scoop the DMSO cream into another bowl and mix in the DMSO/sirolimus thoroughly and place back into the original container and label it as containing 3mg sirolimus. With the expected wastage this will give you about 25 micromolar topical for a cost of about $33.60 plus the cost of rapamycin which is about $1 per milligram from Tailor Made, more or less from other supplies. My total cost is $36.60. The amount of grams in the 4 ounce cream tub is 118. So I am able to easily create the equivalent of four 30 gram containers of more potent (25 micromolar) topical for the cost one less potent (11 micromolar) topical from Tailor Made.

garland Noticed a error in my prior post on the topical formula. Funny how my mind came back to this one day later as if it was bothering me. The total amount of sirolimus reguired in all 5 of your 30gram containers (150grams) is 3.4mg. Since the .001% already contains 1.5mg, you only need to add 1.9mg which is close enough to 2mg to just make it an even 2mg. If you already mixed it as I stated in previous post, it would be 33 micromolar which is about 3X the potency of the original.

This is also probably OK but I just can't speak to it in terms of personal experience because mine is 25 micromolar. I've now applied to face, neck, and the back of one hand an average of 1.7 times per day for about 4 months. Others for whom I have provided this have been applying 1-2 times daily for about 3 months. Observable effects are becoming more obvious and clear in that there is a reversal of skin aging. Skin thickness and wrinkles are markedly improved, age spots are fading, the people using it, myself included, look younger.

Word of caution - avoid applying to close to the hairline as this concentration is predicted to slow down hair growth because follicles require adequate mtor activity. I have noticed my facial hair has a decreased growth and I no longer have 5 oclock shadow and it is easier to shave in the am. I do apply a 2 micromolar solution to scalp and this is predicted to mainly effect autophagy which improves growth (induces anagen) and enhances melanocyte activity. Observations seem to indicate increased thickness and more black hair versus gray.

It is all quite interesting and somewhat fun to observe these effects.

Mark Thimineur Thanks a bunch for the increased clarity on what you do. So much of the time you do the solution 2 times a day rather then  one time. I am sure that makes a huge difference. I just put my order in for the DMSO and Aloe etc. Interesting Amazon is now pairing them together so that tells me that plenty of people are now doing this. I guess you are making a difference!!! 

I also take Hyaluronic acid.... should I put that on before I do the topical solution or afterwords? I am starting to think that I should do that afterwords.... but wondered if you have any experience with adding other things? 

Pertaining to the applying it to the scalp for the hair. I gather that the topical cream supplied by Taylor Made would be too strong for that purpose? Or would it be close enough we could use it? 

I am still seeing if my doctor will give me a prescription for Rapamyacin from Taylor Made. She evidently talked with the pharmacist for a good while on Friday so I should know what the verdict is tomorrow. 

garland the 11 micromolar Tailor Made would be to strong for scalp. My 2 micromolar is made by adding 0.2 mg sirolimus to 100ml DMSO and using the pump spray attachment that comes with the bottle to spray on hair then rub into scalp. It stings a little at first

I can’t comment specifically about co-administration with hylaronic cuz i don’t use that product. I would suggest that you apply sirolimus first and give it an hour before applying anything else.

I use two products in addition to sirolimus which I have used for years. They are Differin (Adapalene) 0.1% and lifeline skin care - the basic original stem cell product. Both of these have sound science behind them and are proven to work on fine wrinkles. The Differin should be applied at night and will take 3-5 weeks before you desensitize to the drying effect, after that no problem. The lifeline product can be used anytime. Btw, the sirolimus blows these others away but I feel that attacking skin aging via three distinct mechanisms is still advantageous

Mark Thimineur Wow... which of the Life Skin products  with stem cells do you suggest? I have tried all kinds of things to work with my skin damage from the sun and nothing really helped very much.  I tried the life extension with stem cells and nothing happened...  HOwever I am Doing some laser now and am getting much more results that way...but still  more is needed....so this is very encouraging that the Sirolimus blows the others away

garland Laser resurfacing and microneedling work because they create microscopic areas of injury in the epidermis which promotes collagen production and this technique is proven to improve the appearance of sun damaged skin and scarring.

Dermal mtor inhibition and induction of autophagy with topical sirolimus involves inhibition of senescent fibroblasts and (it seems) eliminating senscent cells from the dermis/epidermis. The net effect is greater collagen production which is better organized, rejuvenation of skin stem cells, and repair and organization of the basement membrane. There are probably other mechanisms at play as well.

In vitro (skin cell cultures) there also appears to be a protective effect in skin fibroblasts from solar radiation damage. "Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species" Cell Physiol Biochem 2018;46:1849–1860. 

Last summer my spouse and I became quite lax about applying sunscreen when boating and beaching as we noticed we seemed not to sunburn. I've tested this observation this winter on our many trips to the carribean and noted I needed less suncreen than previous and it really took alot of sun to get any kind of burn. We have been taking oral sirolimus between 0.08-0.18mg/kg weekly for about one year.

I have performed about 30,000 flouroscopy guided medical procedures in my medical career in which my hands have been in the radiation beam. Between my enjoyment of the sun and the repetitive exposure to xray, my hands show significant radiation induced aging. I now see in my sirolimus treated right hand a progressive improvement in the skin compared to the untreated left side which has become pretty impressive at 4 months. 

My opinion at this point is that the topical sirolimus appears to be among the most robust (if not the best) treatment for skin aging. It takes time as it does not induce it as quickly as laser but I'm observing a far greater net effect with the twice daily application than other techniques I have observed. I know a few plastic surgeons who would not like this to be known widely.

The lifeline skin care product is either their "daily defense" or "night recovery" I would say these help, but nothing like the sirolimus. They are also a little expensive. I just use them because they work through a different mechanism as well as the differin which works as a retin-A product which increases cell turnover. Hope all this helps