51 replies to this topic

[meatsauce]

http://www.sciencema...igns-aging-mice

 

From the article:

 

Senescent cells carry the type of DNA damage that should spur a protective protein, called p53, to put them down. Instead, the researchers found that a different protein, FOXO4, latches onto p53 and prevents it from doing its duty.

 

To counteract this effect, De Keizer and colleagues designed a molecule, known as a peptide, that carries a shortened version of the segment of FOXO4 that attaches to p53. In a petri dish, this peptide prevented FOXO4 and p53 from hooking up, prompting senescent cells to commit suicide. But it spared healthy cells.  

 

Im thinking we could get this peptide made if people would be willing to try it. 

We would need to figure out what the peptide sequence is. Anyone want to help?

Edited by meatsauce, 11 April 2017 - 09:52 PM.

[Rocket]

Hi Meatsauce. This was discussed in the bioscience section. I think the consensus from more knowledgeable people is that this peptides is hard to manufacture and $$$.

[meatsauce]

Ok thanks rocket. 

[Chroma]

I found a source that sells it, but expensive at the moment. But if we wait a while and the research peptide sellers have it in stock it will be 30-50 dollar for a 5mg bottle.

 

I think it is the best change at the moment for removing senescent cells and ultimaly if it works on humans the same (i think so, if you inject it subq) a change to reverse some of the 'damage'.

 

5mg is for testing on big animals i think :p

 

Don't know if i can share the link here, but will see.

https://www.novoprol...ide-318716.html

Edited by Chroma, 16 April 2017 - 08:29 PM.

[Chroma]

Hi Meatsauce. This was discussed in the bioscience section. I think the consensus from more knowledgeable people is that this peptides is hard to manufacture and $$$.

 

Strange, it is not so difficult to make compared to much bigger peptides, this one is relatively small. With big i mean 300-400 amino acids.

 

But around 40 amino acids is not to expensive to make. The link i posted is a company that is using the moment when it is not readily available to ask more money..

 

Peptide sequence is also in the link and attached it as a file. Has to be freeze dried like every other peptide and you mix it with 1ml of nacl 0,9% sterile water (or bac water) for subqutaneous injection.

 

 

Attached Files

•  Foxo4 dri peptide.jpg   84.7KB   15 downloads

Edited by Chroma, 16 April 2017 - 08:45 PM.

[aconita]

Novopro is China based, successful shipping into UE is unlikely or at least quite unreliable. 

[Chroma]

Novopro is China based, successful shipping into UE is unlikely or at least quite unreliable. 

 

Most peptides are being produced in China, you have some US based companies but i wouldn't say they are more reliable. Also shipping from US can be checked by customs if you send with normal postal service.

 

Research peptide companies based in EU (en UK) sell peptides rom China or US. Normally they will have it in stock in a few weeks or months (hopefully weeks).

 

If you use fedex or dhl the succes rate is much higher, even from China.

[malbecman]

 Along these lines, this paper in Cell (which is a top tier journal) also came out recently.   This peptide looks promising

 

Cell. 2017 Mar 23;169(1):132-147.e16. doi: 10.1016/j.cell.2017.02.031.

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.

Baar MP¹, Brandt RM¹, Putavet DA¹, Klein JD¹, Derks KW¹, Bourgeois BR², Stryeck S², Rijksen Y¹, van Willigenburg H¹, Feijtel DA¹, van der Pluijm I³, Essers J⁴, van Cappellen WA⁵, van IJcken WF⁶, Houtsmuller AB⁵, Pothof J¹, de Bruin RW⁷, Madl T², Hoeijmakers JH¹, Campisi J⁸, de Keizer PL⁹.

Author information

Abstract

The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging. Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging. Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored. Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53. In senescent cells, this selectively causes p53 nuclear exclusion and cell-intrinsic apoptosis. Under conditions where it was well tolerated in vivo, this FOXO4 peptide neutralized doxorubicin-induced chemotoxicity. Moreover, it restored fitness, fur density, and renal function in both fast aging Xpd^TTD/TTD and naturally aged mice. Thus, therapeutic targeting of senescent cells is feasible under conditions where loss of health has already occurred, and in doing so tissue homeostasis can effectively be restored.

Copyright © 2017 Elsevier Inc. All rights reserved.

KEYWORDS:

FOXO4; IL6; LMNB1; Senescence; TP53; aging; apoptosis; cell-penetrating peptide; chemotherapy; tissue homeostasis

PMID: 28340339

[Turnbuckle]

A patent application associated with the paper in the OP--

 

ANIMAL MODELS OF AGE-RELATED DISORDERS AND AGE-SENSITIVE TRAITS ASSOCIATED WITH SENESCENCE-INDUCING STIMULI AND USES THEREOF 

[meatsauce]

This patent has the "entire 9267 nt sequence" I'm not sure what that's referring to. The article that was published in CELL has the peptide as: FOXO4 D-Retro-Inverso peptide H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH

 

They do not mention the doses that were given to the mice in the study. 

 

One of the people involved might be able to give us an answer. 

 

Depending on the dose this could cost a lot or be manageable. Even if it is expensive paying lets say $1000 wouldn't be too bad for an effective cycle of killing senescent cells without doing damage to normal cells according to the in vivo mouse studies.

 

Who would be willing to try if we could get it?

Edited by meatsauce, 28 April 2017 - 09:46 PM.

[Chroma]

I checked the price for 1 grams, it is very expensive at the moment.

 

-FOXO4-DRI TFA Salt (not freeze-dried or sterile) is 11800 dollar/g (+95% purity)

-FOXO4-DRI Acetate Salt (also not freeze-dried or sterile) is 14000 dollar/g (+95% purity)

 

I also asked today a quota for freeze-dried (lyophilized) because it is much more stable for transport and sterile so you don't have to use filters first. Will keep updated.

 

Normally peptides are sold in 5-10mg bottles, but the question is how much do you have to use. But if you could get 50mg for a reasonable price then you could do some testing.

 

 

[Freebytes]

I was very excited to see what comes of this since I first heard about it.

 

[Alpharius]

I checked the price for 1 grams, it is very expensive at the moment.

 

-FOXO4-DRI TFA Salt (not freeze-dried or sterile) is 11800 dollar/g (+95% purity)

-FOXO4-DRI Acetate Salt (also not freeze-dried or sterile) is 14000 dollar/g (+95% purity)

 

I also asked today a quota for freeze-dried (lyophilized) because it is much more stable for transport and sterile so you don't have to use filters first. Will keep updated.

 

Normally peptides are sold in 5-10mg bottles, but the question is how much do you have to use. But if you could get 50mg for a reasonable price then you could do some testing.

 

Without digging further into the details, but this peptide is made to block the binding of FOXO4 to P53 and to interrupt this connection. The amino acid sequence of the peptide in the paper has for sure been chosen to reflect the amino acid sequence of the mouse FOXO4/P53 binding site.

 

Has anybody here checked, that this part of the sequence is identic in humans too?
Plus as far as I remember it had something (a further peptide sequence) attached to it in order to enhance the absorption by the cells or not?

From the paper: 

FOXO4 D-Retro-Inverso peptide development FOXO4-DRI consists of the following amino acid sequence in D-Isoform: H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH. MW: 5358.2 It was manufactured by Pepscan (Lelystad, the Netherlands) at > 95% purity and stored at 20C in 1mg powder aliquots until used to avoid freeze-thawing artifacts. For in vitro experiments FOXO4-DRI was dissolved in PBS to generate a 2mM stock. For in vivo use, FOXO4-DRI was dissolved in PBS to generate a 5mg/ml stock solution, which was kept on ice until injection. Before injection the solution was brought to room temperature.

[Alpharius]

Ok I checked the paper again. The sequence is the same in mice and human:
hsFOXO4 (NP_005929) PRKGGS-RRNAWGNQSYAELISQAIESAPEKRLT 33

mmFOXO4 (NP_061259) PRKGGS-RRNAWGNQSYAELISQAIESAPEKRLT 33

They attached HIV-TAT a hydrophilic amino acid sequence which allows the peptide to enter cells better. I am just not sure if they only used the additional sequence for the in vitro cell experiments or in the vivo experiments in mice too. Will read the paper tomorrow full and look if its possible to find out.
 

[meatsauce]

Ok I checked the paper again. The sequence is the same in mice and human:
hsFOXO4 (NP_005929) PRKGGS-RRNAWGNQSYAELISQAIESAPEKRLT 33

mmFOXO4 (NP_061259) PRKGGS-RRNAWGNQSYAELISQAIESAPEKRLT 33

They attached HIV-TAT a hydrophilic amino acid sequence which allows the peptide to enter cells better. I am just not sure if they only used the additional sequence for the in vitro cell experiments or in the vivo experiments in mice too. Will read the paper tomorrow full and look if its possible to find out.
 

 Good thinking about checking the human sequence. I think the most important question now is knowing the dosage they used. 

[Chroma]

Ok I checked the paper again. The sequence is the same in mice and human:
hsFOXO4 (NP_005929) PRKGGS-RRNAWGNQSYAELISQAIESAPEKRLT 33

mmFOXO4 (NP_061259) PRKGGS-RRNAWGNQSYAELISQAIESAPEKRLT 33

They attached HIV-TAT a hydrophilic amino acid sequence which allows the peptide to enter cells better. I am just not sure if they only used the additional sequence for the in vitro cell experiments or in the vivo experiments in mice too. Will read the paper tomorrow full and look if its possible to find out.
 

 

It is indeed the same sequence with humans.

 

This is the full sequence of the peptide they used:

 

H-LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG-OH
 

[Alpharius]

The mice were injected IV with 5 mg/kg FOXO4-DRI, every other day (day 1, 3, and 5) for the experiment where they gave FOXO4-DRI to minimize damage done by Doxorubicin treatment. That would be a human equivalent dose (HED) of 0,4 mg/kg. Means if you weigh around 80 kg, you need 32 mg of the peptide.

 

Just one question remains: Do they used FOXO4-DRI in vivo and FOXO4-DRI with HIV-TAT in vitro for better detection with antibodies which were aimed at HIV-TAT?
To me it seems in vivo they used just the pure version without anything attached.

Also very nice is the fact that FOXO4-DRI seems to hit more SASP-senescent cells then "sterile" senescent cells which do not secret that much of inflammatory factors. Also they could show that if they would boost the SASP in these cells they were more efficiently killed by the peptide. Antiinflammatory medications diminished the efficiency. 

 

Edited by Alpharius, 03 May 2017 - 05:01 PM.

[meatsauce]

So I wonder If the Human equivalent dose applies to peptides like this. I hope so. 

 

I remember reading that they saw significant changes in the mice within about a week so maybe that is all we would need depending on our age. 

 

If this works in humans it would be a great thing to do a cycle of once per year. 

[Alpharius]

From an additional paper summarizing the original one, some thoughts and concerns: 
 

 

However, we will first need to get better insight into the potential short- and long-term side effects. In view of the strong affinity of FOXO4-DRI to p53, one would like to know whether FOXO4-DRI binding to p53 modulates its functions in normal cells, causing unwanted side effects that only become apparent in the longer term or under specific conditions. Could it be that treatment with FOXO4-DRI causes rare senescent cells carrying oncogenic lesions, such as those found in nevi, to re-enter the cell cycle rather than undergo apoptosis, thereby increasing the risk of tumor development? One would also like to know more about the pharmacokinetic properties of FOXO4-DRI and whether it is immunogenic, as the latter would limit its repeated use. Otherwise it might be wiser to focus on the development of small-molecule drugs with similar activity and specificity.

 

 

And they say the FOXO4-DRI was fused with HIV-TAT and then injected into the mice.

 

https://www.ncbi.nlm...pubmed/28340347

[malbecman]

 I would agree...while the peptide looks very promising, it also appears to be pretty potent and I, personally, would like to see some more studies addressing these potential issues before injecting myself.

 

From an additional paper summarizing the original one, some thoughts and concerns: 
 

 

However, we will first need to get better insight into the potential short- and long-term side effects. In view of the strong affinity of FOXO4-DRI to p53, one would like to know whether FOXO4-DRI binding to p53 modulates its functions in normal cells, causing unwanted side effects that only become apparent in the longer term or under specific conditions. Could it be that treatment with FOXO4-DRI causes rare senescent cells carrying oncogenic lesions, such as those found in nevi, to re-enter the cell cycle rather than undergo apoptosis, thereby increasing the risk of tumor development? One would also like to know more about the pharmacokinetic properties of FOXO4-DRI and whether it is immunogenic, as the latter would limit its repeated use. Otherwise it might be wiser to focus on the development of small-molecule drugs with similar activity and specificity.

 

 

And they say the FOXO4-DRI was fused with HIV-TAT and then injected into the mice.

 

https://www.ncbi.nlm...pubmed/28340347

 

[Andey]

 

 I would agree...while the peptide looks very promising, it also appears to be pretty potent and I, personally, would like to see some more studies addressing these potential issues before injecting myself.

 

From an additional paper summarizing the original one, some thoughts and concerns: 
 

 

However, we will first need to get better insight into the potential short- and long-term side effects. In view of the strong affinity of FOXO4-DRI to p53, one would like to know whether FOXO4-DRI binding to p53 modulates its functions in normal cells, causing unwanted side effects that only become apparent in the longer term or under specific conditions. Could it be that treatment with FOXO4-DRI causes rare senescent cells carrying oncogenic lesions, such as those found in nevi, to re-enter the cell cycle rather than undergo apoptosis, thereby increasing the risk of tumor development? One would also like to know more about the pharmacokinetic properties of FOXO4-DRI and whether it is immunogenic, as the latter would limit its repeated use. Otherwise it might be wiser to focus on the development of small-molecule drugs with similar activity and specificity.

 

 

And they say the FOXO4-DRI was fused with HIV-TAT and then injected into the mice.

 

https://www.ncbi.nlm...pubmed/28340347

 

  Possibilitys of something severe are quite low as 1) its obviosly not toxic 2) Binding to p53 is transient 

As for me the biggest risk if there is some type of cells in human body that are exhibit same pattern as senescent ones and there would be mass death of functional cells.

But...there would be always some brave person who would try it first, and hopefully that experience would remove majority of this fears.

[malbecman]

 I have just setup a PubMed alert for FOXO4-DRI and just got this newer paper.  Its in vivo and also looks promising:

 

A FOXO4 Inhibitory Peptide Limits Chemotoxicity in Mice.

 

Cancer Discov. 2017 Apr 7. doi: 10.1158/2159-8290.CD-RW2017-066. [Epub ahead of print]

PMID: 28389573

 

 

 

• Major finding: The FOXO4 inhibitory peptide FOXO4-DRI promotes targeted apoptosis of senescent cells.

• Mechanism: FOXO4-DRI disrupts the FOXO4–p53 interaction to promote nuclear exclusion of p53 in senescent cells.

• Impact: Therapeutic targeting of senescent cells may reverse the effects of chemotoxicity and aging.

Senescent cells develop a senescence-associated secretory phenotype (SASP), a persistent proinflammatory phenotype that may contribute to accelerated aging and chemotoxicity. However, it is not known how cells avoid apoptosis to undergo senescence or whether targeting senescent cells could counteract the effects of accelerated aging and chemotoxicity. Baar and colleagues found that despite their resistance to apoptosis, senescent fibroblasts exhibited an upregulation of the proapoptotic proteins PUMA and BIM, and a downregulation of the antiapoptotic protein BCL2. FOXO4 was upregulated in senescent cells and FOXO4 depletion prior to the induction of senescence induced apoptosis, whereas FOXO4 depletion in senescent cells reduced cell viability, indicating that FOXO4 may repress apoptosis to maintain the viability of senescent cells. FOXO4 localized to senescence-associated promyelocytic leukemia bodies that fused to 53BP1-containing DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS) to regulate SASP. p53 associates with the DNA-SCARS in senescent cells and interacts with FOXO4, and, as p53 regulates apoptosis and senescence, these findings suggested the potential for therapeutic targeting of the FOXO4–p53 interaction. A FOXO4 inhibitory peptide, FOXO4-DRI, was designed that disrupted the FOXO4–p53 interaction, which resulted in nuclear exclusion of active p53 and the induction of p53-dependent apoptosis in senescent cells. In vivo, FOXO4-DRI reversed doxorubicin-induced chemotoxicity, including increasing body weight and reducing levels of the liver damage indicator aspartate aminotransferase. Further, FOXO4-DRI counteracted the negative effects of senescence in mouse models of natural and accelerated aging. In addition to generating an inhibitory FOXO4 peptide that disrupts the interaction with p53 to induce apoptosis of senescent cells, these findings indicate that senescent cells may be therapeutically targeted to reverse the effects of chemotoxicity and aging.

[pieter cloete]

Some interesting reading

A Broadening of Efforts to Clear Senescent Cells
https://www.fightagi...enescent-cells/

An Example of Senolytic Self-Experimentation with FOXO4-DRI
https://www.fightagi...with-foxo4-dri/

It seems that slowly the rout to stop/reversing aging is shortening. I personally think that the real slowing will be available in about 4 to 8 years and reversing in about 20 years.

[Andey]

 

Some interesting reading

A Broadening of Efforts to Clear Senescent Cells
https://www.fightagi...enescent-cells/

An Example of Senolytic Self-Experimentation with FOXO4-DRI
https://www.fightagi...with-foxo4-dri/

It seems that slowly the rout to stop/reversing aging is shortening. I personally think that the real slowing will be available in about 4 to 8 years and reversing in about 20 years.

 

 

Nice. 

Some info available at http://foxo4dri.com/

Edited by Andey, 22 May 2017 - 12:12 PM.

[meatsauce]

So there is the guy from Foxo4dri.com taking 30 - 50mg at a time a few times a week and there is another guy named Steve that have apparently taken only 1 mg of this stuff and has seen positive changes:

 

 "When I started adding the FOXO4-DRI in the past week I have noticed some definite changes. Weight loss, better sleep, more endurance and perhaps an improvement in lung function now well over 100% for the 3 measures, FVC, FEV and PEF, for a 63 yo. I know that the dose, a little less than 1 mg over 7 days, is a lot lower than the threshold dose indicated by the mouse model of .4 mg per kg of body weight for a human but I can’t reconcile my results with simply a placebo effect."

 

Its an expensive peptide it seems. We really don't know what the minimal effective dose is in human. Im not too sure how they came up with the mouse dose but it could very well be that the same results could have been had with much less than they were using. 

 

I am thinking about taking 100mg over 10-20 days.  I need to buy more at a time to make this cost effective. Who is willing to spend around 700-1000 dollars on 100mg? I think its a small price to pay considering what it can potentially do for us. 

[Andey]

So there is the guy from Foxo4dri.com taking 30 - 50mg at a time a few times a week and there is another guy named Steve that have apparently taken only 1 mg of this stuff and has seen positive changes:

 

 "When I started adding the FOXO4-DRI in the past week I have noticed some definite changes. Weight loss, better sleep, more endurance and perhaps an improvement in lung function now well over 100% for the 3 measures, FVC, FEV and PEF, for a 63 yo. I know that the dose, a little less than 1 mg over 7 days, is a lot lower than the threshold dose indicated by the mouse model of .4 mg per kg of body weight for a human but I can’t reconcile my results with simply a placebo effect."

 

Its an expensive peptide it seems. We really don't know what the minimal effective dose is in human. Im not too sure how they came up with the mouse dose but it could very well be that the same results could have been had with much less than they were using. 

 

I am thinking about taking 100mg over 10-20 days.  I need to buy more at a time to make this cost effective. Who is willing to spend around 700-1000 dollars on 100mg? I think its a small price to pay considering what it can potentially do for us. 

 

  30mg for $300 would be ok for me. Its a nice goal for a group buy. 

  If you translate mouse dosage to human ones it would be around 30-50 mg depending on your surface area (or weight for simplicity). 30mg would be conservative estimate.

  I see no particular reason to why it should not work from one single dose. small dosages should work too but it would be less likely  to reach brain or prostate or other hard to reach organs.

  Or two dosages - one small to test individual reactions and to reduce stress for body to utilize a lot of senescent cells at once, and proper second one. 

[meatsauce]

 

So there is the guy from Foxo4dri.com taking 30 - 50mg at a time a few times a week and there is another guy named Steve that have apparently taken only 1 mg of this stuff and has seen positive changes:

 

 "When I started adding the FOXO4-DRI in the past week I have noticed some definite changes. Weight loss, better sleep, more endurance and perhaps an improvement in lung function now well over 100% for the 3 measures, FVC, FEV and PEF, for a 63 yo. I know that the dose, a little less than 1 mg over 7 days, is a lot lower than the threshold dose indicated by the mouse model of .4 mg per kg of body weight for a human but I can’t reconcile my results with simply a placebo effect."

 

Its an expensive peptide it seems. We really don't know what the minimal effective dose is in human. Im not too sure how they came up with the mouse dose but it could very well be that the same results could have been had with much less than they were using. 

 

I am thinking about taking 100mg over 10-20 days.  I need to buy more at a time to make this cost effective. Who is willing to spend around 700-1000 dollars on 100mg? I think its a small price to pay considering what it can potentially do for us. 

 

  30mg for $300 would be ok for me. Its a nice goal for a group buy. 

  If you translate mouse dosage to human ones it would be around 30-50 mg depending on your surface area (or weight for simplicity). 30mg would be conservative estimate.

  I see no particular reason to why it should not work from one single dose. small dosages should work too but it would be less likely  to reach brain or prostate or other hard to reach organs.

  Or two dosages - one small to test individual reactions and to reduce stress for body to utilize a lot of senescent cells at once, and proper second one. 

 

It seems like the mice saw the most improvement within the first 10 days if I remember correctly. They gave them multiple doses throughout the month I think. Why do you think 1 dose would be enough? I think that if we want to kill the majority of senescent cells then the peptide needs to get into every cell. One dose of 30 mg might not be able to do that. 

[Andey]

It seems like the mice saw the most improvement within the first 10 days if I remember correctly. They gave them multiple doses throughout the month I think. Why do you think 1 dose would be enough? I think that if we want to kill the majority of senescent cells then the peptide needs to get into every cell. One dose of 30 mg might not be able to do that. 

 

 

As I understand it the whole idea is to trigger apoptosis. Most likely every consequent dosage after the first had diminishing effect.

Effect in 10 days is kinda immidiate if you consider that body should process a lot of byproducts of apoptosis, clean up a lot of inflammatory cytokines that was produced during apoptosis, and cells near by probably must divide to preserve tissue integrity. 

 Take my words with a grain of salt, its just a guess from my uneducated perspective

[Chroma]

So there is the guy from Foxo4dri.com taking 30 - 50mg at a time a few times a week and there is another guy named Steve that have apparently taken only 1 mg of this stuff and has seen positive changes:

 

 "When I started adding the FOXO4-DRI in the past week I have noticed some definite changes. Weight loss, better sleep, more endurance and perhaps an improvement in lung function now well over 100% for the 3 measures, FVC, FEV and PEF, for a 63 yo. I know that the dose, a little less than 1 mg over 7 days, is a lot lower than the threshold dose indicated by the mouse model of .4 mg per kg of body weight for a human but I can’t reconcile my results with simply a placebo effect."

 

Its an expensive peptide it seems. We really don't know what the minimal effective dose is in human. Im not too sure how they came up with the mouse dose but it could very well be that the same results could have been had with much less than they were using. 

 

I am thinking about taking 100mg over 10-20 days.  I need to buy more at a time to make this cost effective. Who is willing to spend around 700-1000 dollars on 100mg? I think its a small price to pay considering what it can potentially do for us. 

 

I'm in. I tested 5mg, 150mcg a day and noticed positive effects. Tested a lot of others peptides and substances and this is very different. More energy, more fat (i have an immune dysfunction which makes me very skinny, also a muscle and nerve disorder). So no placebo for me :p

 

Dose was to low for more profound effects, but think it could work much better at higher dose.

 

Edited by Chroma, 24 May 2017 - 08:13 PM.

[meatsauce]

 

So there is the guy from Foxo4dri.com taking 30 - 50mg at a time a few times a week and there is another guy named Steve that have apparently taken only 1 mg of this stuff and has seen positive changes:

 

 "When I started adding the FOXO4-DRI in the past week I have noticed some definite changes. Weight loss, better sleep, more endurance and perhaps an improvement in lung function now well over 100% for the 3 measures, FVC, FEV and PEF, for a 63 yo. I know that the dose, a little less than 1 mg over 7 days, is a lot lower than the threshold dose indicated by the mouse model of .4 mg per kg of body weight for a human but I can’t reconcile my results with simply a placebo effect."

 

Its an expensive peptide it seems. We really don't know what the minimal effective dose is in human. Im not too sure how they came up with the mouse dose but it could very well be that the same results could have been had with much less than they were using. 

 

I am thinking about taking 100mg over 10-20 days.  I need to buy more at a time to make this cost effective. Who is willing to spend around 700-1000 dollars on 100mg? I think its a small price to pay considering what it can potentially do for us. 

 

I'm in. I tested 5mg, 150mcg a day and noticed positive effects. Tested a lot of others peptides and substances and this is very different. More energy, more fat (i have an immune dysfunction which makes me very skinny, also a muscle and nerve disorder). So no placebo for me :p

 

Dose was to low for more profound effects, but think it could work much better at higher dose.

Cool. Yea you seeing positive effects at this low dose makes me think relatively much larger doses are not required. Ok I am starting to find the right supplier for this. I hope we can get at least 10 people wanting to try.