848 replies to this topic

[Madfern]

Seems like most of us are taking 100mg (3X33mg).  Can anyone provide an educated guess, based on the study, what the dose size and intervals would be to come close to replicating?  I assume this amount is not close to that.

 

If all goes well, I'd like to do this as often as I can afford to get close to the study amounts.  That may be only on a yearly basis due to cost, which could complicate the comparison.

 

According to https://www.fightagi...tide-foxo4-dri/ the human equivalent dose for a 60kg human is 25mg.  33mg would be if you weigh 80kg.

 

Rather than taking the plunge with the full dose, I am planning on starting with 1mg and then successively doubling the dose until I get into the 33mg target range.  That way adverse reactions should show up earlier.

 

If the treatment works, you should not have to repeat it for at least a year (probably a few years).

[OP2040]

 

 

Thanks, I just realized this question was answered previously in the thread. 

 

I guess I'm having trouble wrapping my head around it because it all seems so great.  If this is the proper dose and only has to be done every 5 years or so at most, it will be very affordable.  And if it actually does work exactly as it does in mice (a big if) then this is one of the hallmarks of aging checked off the list, just like that.  That is an amazing possibility!

[Rocket]

 

 

 

Thanks, I just realized this question was answered previously in the thread. 

 

I guess I'm having trouble wrapping my head around it because it all seems so great.  If this is the proper dose and only has to be done every 5 years or so at most, it will be very affordable.  And if it actually does work exactly as it does in mice (a big if) then this is one of the hallmarks of aging checked off the list, just like that.  That is an amazing possibility!

 

 

You will still age, wrinkle, gray, lose muscle mass and become frail and suffer from a host of ageing issues including immune system decline and much more. You will, if the product is real and works in humans, have some healthier biomarkers.

 

I suspect that SASP affects creatures whose bodyweight is measure in grams much more strongly than a creature whose bodyweight is hundreds and hundreds of times greater. Show me the same results in primates, please.

 

I also suspect the dosages that people have calculated from mice-to-men is much too low. It should probably be scaled up 1:1 with bodyweight. This isn't aspirin after all or something being digested by the gut...

 

 

Edited by Rocket, 04 April 2018 - 01:40 PM.

[OP2040]

I just received my package and am waiting a couple weeks for NSAIDs and supplements to clear out of my system.

 

In the mean time, I generally fast 14-16 hours a day. In part prompted by articles I read a few years ago on autophagy and fasting (not to mention that was generally the way I ate when I was younger and thinner and microwave ovens were just a twinkle in some engineers eye.) I was pondering whether to continue this fasting cycle when taking FOXO4. Attempting to look up articles about autophagy and senescence only seems make the picture more confusing. Does anyone here with a bit more experience have any insight into the topic.

 

It seems like just a bit of logic should guide us on this one.  If anything, clearing senescent cells and autophagy are complementary.  Upgrading autophagy is a known mechanism for increasing health and lifespan.  However, I've also read that too much autophagy can induce the inflammatory responses, which sounds a lot like senescent cells and SASP to me.  So if you are upgrading autophagy for example with a CR mimetic, then the best thing you could do at this point is clear out the senescent cells and hopefully the inflammation that they cause. 

 

Whether you take a break from any autophagy-enhancers is really irrelevant.  More relevant would be whether you take them at all.  And if you do, then FOX04 would be a great thing to do as a next step.  The worry according to the current theories should be stem cell exhaustion and cell atrophy.  Basically, we are getting really good at one side of the aging equation (clearing out the damage), but not quite there with the other side of the equation (regenerating tissues).  So tissue atrophy might be something to look out for in the future, but luckily this is something that probably has it's effect much later than senescence/junk/inflammation. 

[OP2040]

 

 

 

 

Thanks, I just realized this question was answered previously in the thread. 

 

I guess I'm having trouble wrapping my head around it because it all seems so great.  If this is the proper dose and only has to be done every 5 years or so at most, it will be very affordable.  And if it actually does work exactly as it does in mice (a big if) then this is one of the hallmarks of aging checked off the list, just like that.  That is an amazing possibility!

 

 

You will still age, wrinkle, gray, lose muscle mass and become frail and suffer from a host of ageing issues including immune system decline and much more. You will, if the product is real and works in humans, have some healthier biomarkers.

 

I suspect that SASP affects creatures whose bodyweight is measure in grams much more strongly than a creature whose bodyweight is hundreds and hundreds of times greater. Show me the same results in primates, please.

 

I also suspect the dosages that people have calculated from mice-to-men is much too low. It should probably be scaled up 1:1 with bodyweight. This isn't aspirin after all or something being digested by the gut...

 

 

Absolutely agree on the facts, but not on the sentiment.  You will still age, but the increased healthspan would be a pretty huge deal for most people. 

 

Also, I think rapid advances are masked by the fact that combinations have not been tested yet.  Once we can address a few of these hallmarks at the same time, that is when we will see a quantum leap in effect.  That is when we will see the things people are looking for like reversal of balding and wrinkles.  That is the point where it will become very obvious rather than ambiguous. 

 

Immune system decline does seem like a special case.  It is likely the reason most conventional therapies work pretty well in a younger person than the elderly.  With cancer for example, many of the newer therapies have the potential to be transformative, if you have a functioning immune system.

 

You may be right about the dosing.  It would be great if there was a cheap and easy way to measure senescent cell burden.

 

 

[Nate-2004]

I agree with Rocket somewhat that there is too much obsession and focus on senescent cells, the hype is big right now and I just don't think that until we're much older that these do anything more than aggravate/accelerate aging and cause dysfunction later on. 

 

I keep thinking that AGEs, shortening telomeres, stem cell depletion and overall turn over speed (autophagy, etc) which is important for reduction in AGEs should be a bigger focus because that's where we're really seeing youthspan and lifespan extension, cell turnover.

[MikeDC]

I agree with Rocket somewhat that there is too much obsession and focus on senescent cells, the hype is big right now and I just don't think that until we're much older that these do anything more than aggravate/accelerate aging and cause dysfunction later on.

I keep thinking that AGEs, shortening telomeres, stem cell depletion and overall turn over speed (autophagy, etc) which is important for reduction in AGEs should be a bigger focus because that's where we're really seeing youthspan and lifespan extension, cell turnover.

Totally agree. But some people just want to try new things and it is not a matter of improving health.

My health has been greatly improved using NR without killing senescent cells. So even for a 56 year old, senescent cells is not a big issue. Of course I will be very eager to use any drug that has been proven effective in clinical trials. In the meantime, I am buying more time with NR. I expect some kind of senolytics will become available in 10 years. I can wait for it even at my age. Younger people are better off using NR to prevent senescent cells and rejuvenate them if you do have.

[OP2040]

I agree with Rocket somewhat that there is too much obsession and focus on senescent cells, the hype is big right now and I just don't think that until we're much older that these do anything more than aggravate/accelerate aging and cause dysfunction later on. 

 

I keep thinking that AGEs, shortening telomeres, stem cell depletion and overall turn over speed (autophagy, etc) which is important for reduction in AGEs should be a bigger focus because that's where we're really seeing youthspan and lifespan extension, cell turnover.

 

Although we just don't know at this point, I have come to the exact opposite conclusion after reading as much of the material as I can find.  AGE's and especially telomeres seem to me not nearly as important as many of the other hallmarks, senescent cells in particular. 

 

Te Hallmarks of Aging paper is so much more lucid and relevant than the SENS list of aging causes.  And this paper doesn't even mention AGEs directly.  There is really no evidence that they are a major cause of aging.  The interventions in mice did not have anything to do with aging, rather they improved blood pressure, which is also cured in mice with Thioredoxin which has nothing to do with AGEs.  I suppose lack of evidence doesn't mean they are unimportant though.  It just means that we don't know how important.  And given that we have seen various forms of rejuvenation (kidney, vascular, etc.) addressing other hallmarks, but not addressing AGEs at all, makes me think they are way down the list of concerns.

 

As for telomeres, they have had dramatic anti-aging effects in a few studies.  However, I think they are less important than epigenetic aging.  Epigenetic rejuvenation (with OSKM) completely restores cells AND telomoeres.  Telomere rejuvenation only restores cells in a qualified manner, and has pleiotropic effects when it comes to Horvath's clock.  They will probably be important when all is said and done, just not as important.

 

Agree that stem cells and autophagy are quite important.

[MikeDC]

I agree with Rocket somewhat that there is too much obsession and focus on senescent cells, the hype is big right now and I just don't think that until we're much older that these do anything more than aggravate/accelerate aging and cause dysfunction later on.

I keep thinking that AGEs, shortening telomeres, stem cell depletion and overall turn over speed (autophagy, etc) which is important for reduction in AGEs should be a bigger focus because that's where we're really seeing youthspan and lifespan extension, cell turnover.

Although we just don't know at this point, I have come to the exact opposite conclusion after reading as much of the material as I can find. AGE's and especially telomeres seem to me not nearly as important as many of the other hallmarks, senescent cells in particular.

Te Hallmarks of Aging paper is so much more lucid and relevant than the SENS list of aging causes. And this paper doesn't even mention AGEs directly. There is really no evidence that they are a major cause of aging. The interventions in mice did not have anything to do with aging, rather they improved blood pressure, which is also cured in mice with Thioredoxin which has nothing to do with AGEs. I suppose lack of evidence doesn't mean they are unimportant though. It just means that we don't know how important. And given that we have seen various forms of rejuvenation (kidney, vascular, etc.) addressing other hallmarks, but not addressing AGEs at all, makes me think they are way down the list of concerns.

As for telomeres, they have had dramatic anti-aging effects in a few studies. However, I think they are less important than epigenetic aging. Epigenetic rejuvenation (with OSKM) completely restores cells AND telomoeres. Telomere rejuvenation only restores cells in a qualified manner, and has pleiotropic effects when it comes to Horvath's clock. They will probably be important when all is said and done, just not as important.

Agree that stem cells and autophagy are quite important.

Telomere length is not a target for treatment. If cells have high levels of NAD+ and sirtuin activity, telomere length is maintained at levels that doesn’t cause senescence.

[OP2040]

Telomere length is not a target for treatment. If cells have high levels of NAD+ and sirtuin activity, telomere length is maintained at levels that doesn’t cause senescence.

 

 

That's my point.  I forgot that NAD+ also restores telomere length to some extent.  But it certainly is being pursued as a target for treatment by all kinds of people, including serious establishment scientists.

 

There is also the issue of cancer.  Although the catch-22 between cancer and regeneration seems to exist with most of these therapies, it is especially important when it comes to telomeres.  This makes it even less appealing as a target.  Basically, they will be restored anyway, as a result of other therapies, and they run the risk of cancer promotion given the right conditions. 

 

In contrast, eliminating senescent cells seems to avoid the cancer paradox, probably because it is not directly regenerative.  And there is no other therapy target (such as autophagy enhancement), that when applied, also eliminates senescent cells, making them a necessary but not sufficient condition....

 

[Ibbz]

For those who were part of the group buy - any updates on how the injections went / results?

[Rocket]

I agree with Rocket somewhat that there is too much obsession and focus on senescent cells, the hype is big right now and I just don't think that until we're much older that these do anything more than aggravate/accelerate aging and cause dysfunction later on.

I keep thinking that AGEs, shortening telomeres, stem cell depletion and overall turn over speed (autophagy, etc) which is important for reduction in AGEs should be a bigger focus because that's where we're really seeing youthspan and lifespan extension, cell turnover.

Although we just don't know at this point, I have come to the exact opposite conclusion after reading as much of the material as I can find. AGE's and especially telomeres seem to me not nearly as important as many of the other hallmarks, senescent cells in particular.

Te Hallmarks of Aging paper is so much more lucid and relevant than the SENS list of aging causes. And this paper doesn't even mention AGEs directly. There is really no evidence that they are a major cause of aging. The interventions in mice did not have anything to do with aging, rather they improved blood pressure, which is also cured in mice with Thioredoxin which has nothing to do with AGEs. I suppose lack of evidence doesn't mean they are unimportant though. It just means that we don't know how important. And given that we have seen various forms of rejuvenation (kidney, vascular, etc.) addressing other hallmarks, but not addressing AGEs at all, makes me think they are way down the list of concerns.

As for telomeres, they have had dramatic anti-aging effects in a few studies. However, I think they are less important than epigenetic aging. Epigenetic rejuvenation (with OSKM) completely restores cells AND telomoeres. Telomere rejuvenation only restores cells in a qualified manner, and has pleiotropic effects when it comes to Horvath's clock. They will probably be important when all is said and done, just not as important.

Agree that stem cells and autophagy are quite important.

So you if you think AGES are "way down" on the list of aging causes, then you haven't read a paper on AGE accumulation in the heart.... Yeah, AGE accumulation, no big deal!

Yeah, sure, cardiovascular health is way down on my list of things to be concerned about when getting older!

Stiffening soft tissues is a hallmark of aging, I don't know how anyone knowledgeable can argue ottherwise.

Senescent cells are important, but not in your younger years under 40s. People are pumping stuff into their bodies and have no idea what the side effects are or what a correct dose is, all to wipe out nonexistent senescent cells in their youth. Let me know when you 32 year olds revert back to 18.

When they should be more concerned about glycation and stopping it in its tracks, and mitochondrial health, and telomeres, some people here are chasing the bogey man behind the curtains who isn't even there (yet).

Edited by Rocket, 05 April 2018 - 01:05 AM.

[OP2040]

So you if you think AGES are "way down" on the list of aging causes, then you haven't read a paper on AGE accumulation in the heart.... Yeah, AGE accumulation, no big deal!

Yeah, sure, cardiovascular health is way down on my list of things to be concerned about when getting older!

Stiffening soft tissues is a hallmark of aging, I don't know how anyone knowledgeable can argue ottherwise.

Senescent cells are important, but not in your younger years under 40s. People are pumping stuff into their bodies and have no idea what the side effects are or what a correct dose is, all to wipe out nonexistent senescent cells in their youth. Let me know when you 32 year olds revert back to 18.

When they should be more concerned about glycation and stopping it in its tracks, and mitochondrial health, and telomeres, some people here are chasing the bogey man behind the curtains who isn't even there (yet).

 

Way down the list doesn't necessarily mean pointless or irrelevant.  AGEs may accumulate in the heart.  But here is my question.  If AGEs are so important, how can some of the other interventions that show lots of rejuvenation of say heart or kidney without addressing AGEs at all.  I suppose you could say AGEs were addressed by such therapies as well.  The main point being that until I see a study that shows removal of AGEs doing something of an anti-aging or rejuvenating nature in mice, I can't commit to the idea that it is a priority.  And I've changed my mind on this, so I absolutely can change my mind back again if I'm shown the studies.

 

I agree to an extent on the younger people testing on themselves, but ultimately it is their choice.  It's not a choice I would have made at that age.  But then again, I'm 45 and some would consider that still too young, and I certainly do not.  It all depends on your situation.  My criticism is not so much that young and healthy people should not do these things.  It's that when they do, there is probably not going to be much to report.  Although someone made a great point in that they can report side effects, which is a great contribution.  Already, meatsauce who I think is still pretty young, has reported a side effect and that's great information. 

 

Bottom line is that you and I may not be risk takers, but those that are willing to be so should be considered hero's if anything.  It's certainly better than waiting around to age and die while promising therapies go through a tedious 50 year long process toward clinical use.  And of course it matters the particular substances we are talking about.  Taking an educated guess, I am fairly convinced that this will have a reasonable safety profile and therefore worth the risk.  Whereas I never would have participated in any of the Rapamycin ventures.
 

[Rocket]

Way down the list doesn't necessarily mean pointless or irrelevant.  AGEs may accumulate in the heart.  But here is my question.  If AGEs are so important, how can some of the other interventions that show lots of rejuvenation of say heart or kidney without addressing AGEs at all.  I suppose you could say AGEs were addressed by such therapies as well.  The main point being that until I see a study that shows removal of AGEs doing something of an anti-aging or rejuvenating nature in mice, I can't commit to the idea that it is a priority.  And I've changed my mind on this, so I absolutely can change my mind back again if I'm shown the studies.

 

I agree to an extent on the younger people testing on themselves, but ultimately it is their choice.  It's not a choice I would have made at that age.  But then again, I'm 45 and some would consider that still too young, and I certainly do not.  It all depends on your situation.  My criticism is not so much that young and healthy people should not do these things.  It's that when they do, there is probably not going to be much to report.  Although someone made a great point in that they can report side effects, which is a great contribution.  Already, meatsauce who I think is still pretty young, has reported a side effect and that's great information. 

 

Bottom line is that you and I may not be risk takers, but those that are willing to be so should be considered hero's if anything.  It's certainly better than waiting around to age and die while promising therapies go through a tedious 50 year long process toward clinical use.  And of course it matters the particular substances we are talking about.  Taking an educated guess, I am fairly convinced that this will have a reasonable safety profile and therefore worth the risk.  Whereas I never would have participated in any of the Rapamycin ventures.
 

 

Maybe liver failure would be a good result to report too?  At least when people were taking Dasatanib, that is an actual medicine used in people and backed up by clinical trials. This stuff you are buying from China and shooting yourself up with, has been tried in mice. Anyone in their 30s who takes this might as well play Russian roulette with their health.
 

[OP2040]

Maybe liver failure would be a good result to report too?  At least when people were taking Dasatanib, that is an actual medicine used in people and backed up by clinical trials. This stuff you are buying from China and shooting yourself up with, has been tried in mice. Anyone in their 30s who takes this might as well play Russian roulette with their health.
 

 

And yet, we already have several people taking it with only one minor (possibly unrelated) symptom.  If you're trying to tell people they are taking a risk with their lives, I think we would all agree with that.  But that is the choice a hero makes. I'd be more concerned about any potential backlash by the media and scientific community if someone died.  That's what happened with gene therapy and it held off progress for a decade.  So on that level you have a point.

 

But these hysterical reactions, whether by you or the ethical segment of the scientific community are not helpful at all.  As others have said, self experimentation has a long and noble history.  And it involves informed consent by definition.  

 

Here's the part overzealous safety types don't seem to grasp.  This isn't like a car accident that can potentially be completely avoided if we just make the right choices.  Aging and death are a special category which every single one of us will succumb to UNLESS something is done.  That makes the overzealous safety position seem to many of us as irrational. 

 

I laugh sometimes when I listen to the news hysteria.  So some old ladies with macular degeneration get desperate and go to get an experimental stem cell procedure from some sketchy doctor.  These usually fail and sometimes cause complete blindness, but I've seen reports of them also improving eyesight.  So this old lady may not be as informed as us, but is she crazy or reckless?  I say hell no.  Her decision makes perfect sense for her situation.  She is losing her eyesight already, maybe it's already pretty much gone for functional use.  I can't think of any reasonable ethical objection to self-experimentation, and it can be rational in many situations.  So the hysteria needs to stop. 

 

Oh and one final question, our of curiosity.  I am assuming you are younger given your reluctance, so this may not apply to you.  But what would you do if reports here started coming in of dramatically good effects and very few side effects?  You know as well as I do that this will not reach your doctors office for another 20-30 years probably.  Would you wait until you are elderly to take it, just because our system is set up to maximize safety?

[Ibbz]

 

 

Oh and one final question, our of curiosity.  I am assuming you are younger given your reluctance, so this may not apply to you.  But what would you do if reports here started coming in of dramatically good effects and very few side effects?  You know as well as I do that this will not reach your doctors office for another 20-30 years probably.  Would you wait until you are elderly to take it, just because our system is set up to maximize safety?

 

I can only speak for myself, but having to deal with chronic pain every day due to osteoarthritis and chronic tendonopathy when I'm only 33 that I've already dealt with for almost 10 years, I'm looking at every available option out there as there's nothing (with $1000's spent searching and trying different medical therapies) else out there currently that works and I don't want to spend any longer in pain than I have to. There's evidence that senescence is related to the above two conditions so once either phase 1 trials are completed or enough anecdotal evidence is gathered that FOXO4 is reasonably safe, I will certainly be looking at trying it.

 

Senescence clearance doesn't necessarily only relate extending life span / aging - it may have a lot of other positive effects. 

[OP2040]

I can only speak for myself, but having to deal with chronic pain every day due to osteoarthritis and chronic tendonopathy when I'm only 33 that I've already dealt with for almost 10 years, I'm looking at every available option out there as there's nothing (with $1000's spent searching and trying different medical therapies) else out there currently that works and I don't want to spend any longer in pain than I have to. There's evidence that senescence is related to the above two conditions so once either phase 1 trials are completed or enough anecdotal evidence is gathered that FOXO4 is reasonably safe, I will certainly be looking at trying it.

 

Senescence clearance doesn't necessarily only relate extending life span / aging - it may have a lot of other positive effects. 

 

Absolutely!  And I wish you the best.

 

Speaking of which, has anyone else begun taking it?  I just ordered myself, but mine may sit in the freezer until we get a few more self-reports before taking the risk.

[tintinet]

Finished my round last weekend. No major issues. Seemed a to want to sleep more than usual and slept very deeply. Haven’t noticed any other significant changes.

[OP2040]

Finished my round last weekend. No major issues. Seemed a to want to sleep more than usual and slept very deeply. Haven’t noticed any other significant changes.

 

Do you have any health issues that can act as a tracker?  Age?  I completely understand if you want your privacy, but would be really helpful to know these things.  If you're young and healthy, or old and healthy, then it's nice to know your experience for the potential side effects, but not for potential effectiveness.

 

If senescent cells are actually being cleared, they should have a positive effect on almost any tissue function, in theory. 

 

Also, congrats on being a pioneer  

[DareDevil]

Hi friends,

 

I will be taking my three 33mg doses fairly soon. I have already stopped all meds and supplements and am engaged in an intensive junk food regimen attempting to boost inflammation before trial of the Foxo4-DRI from the first Group Buy.

 

Fortunately, I won't shock Rocket or others by dosing more than this or for a longer stretch of time, because it's so darn expensive!

 

And to clarify, I haven't IMHO been reckless with GDF-11. The only "authority" here is patient #0 who has his flock of followers taking such microscopic doses I honestly wonder whether it's worth the trouble given the mild results only visible in slight shifts under lab testing. I use it as a transformational chemical and not a lifelong supplement, and will cease its intake the day I feel more fit. The confusion heard here that I take it as a mood booster, may come from the fact that I noticed that when my intake was high, so were my energy levels, and I used them as an indicator to determine if I should dose or not a given day. I've gone for weeks without a dose, and then taken it every day a subsequent week until I felt "tanked up". It remains residual in your system and I don't think its effects are as much tied to its daily intake as to the levels over time in your body. My usual single intake dose is 100 nanograms, far more than the fraction recommended by Patient #0 who recommends tiny fractions of a single nanogram. For reference for others here who don't know dosage sizes, my dose is a tenth of a microgram, taken every so often. Not exactly a heaping spoonful.

 

I did take too much Dasatinib the second year of my trial.  had only good effects using 40mg/day of pharmaceutical Sprycel for 10 days two years ago. Bumping the dosage to 100mg the last year was too much. My next run will be 50mg for 3 or 4 days, and that's it. I don't think I'm necessarily wanting to dose too high. Only the parameters of optimal dosage aren't yet established with any measure of certainty, and I tend to place effectiveness above extreme caution, hence my forum name.

 

I agree with others here that Senolytics is only a part of the process, and as another member has repeatedly pointed out, we need to kill off senescent cells with senility's, then sweep clean with chelators to finally boost rebuilding with telomere lengtheners and maybe stem cell treatments once these become more readily available and affordable. I hope that some folks here found that the Foxo4-DRI had more than just nice promises without any noticeable positives, because it's a leap of faith to imagine that a substance is doing something significantly in your body if you can't verify the effects. This is partly why I tend to push the dosage envelope for substances with no known danger at high doses, other than precautionary suppositions. That way you can tell what is too much and dial it down. I did exactly that with Rapamycin after a huge canker sore, I cut the dosage in half.

 

Cheers,

 

DareDevil

[chris1299]

Did my 50mg this week, 20mg 4/1 then 30mg on 4/5. Experienced some redness and inflammation around injection site (sub-Q on stomach, left and right of navel), and pain which gradually went away over two days both times. Small lumps now at injection sites—not visible externally, but I can feel them beneath the skin. I was careful with sterility—used bacteriostatic water, needles fresh out of wrapping, clean environment. May have reconstituted with too little fluid.
Both times after injection I became ill with mild flu-like symptoms. Those have mostly subsided by now. Also have been experiencing nausea and constipation. Hard for me to tell if this is just correlation or not—for all I know I happened to get sick independently of the drugs this week. Hopefully more experimenters post, as more data is better and if these symptoms are reported by others perhaps causation can be established (or, better, falsified).

No positive changes to report, but that is to be expected given my age (31). I see that there's been an argument concerning use of these drugs by non-aged individuals on this forum. Here's my rationale: clearance of senescent cells in aged and chemotherapy-treated mice has yielded partial rejuvenation. Great. However, in the original study on mice with progeria (now I can't remember if it was from Mayo clinic or Harvard) it was found that clearance of senescent cells from youth prevented appearance of any phenotypic traits of aging whatsoever.
Of course, taking an experimental drug is a huge risk. For personal reasons, I chose to take that risk in full awareness that there may be no positive effects, and that waiting longer might be a more reasonable strategy.

[Andey]

Did my 50mg this week, 20mg 4/1 then 30mg on 4/5. Experienced some redness and inflammation around injection site (sub-Q on stomach, left and right of navel), and pain which gradually went away over two days both times. Small lumps now at injection sites—not visible externally, but I can feel them beneath the skin. I was careful with sterility—used bacteriostatic water, needles fresh out of wrapping, clean environment. May have reconstituted with too little fluid.
Both times after injection I became ill with mild flu-like symptoms. Those have mostly subsided by now. Also have been experiencing nausea and constipation. Hard for me to tell if this is just correlation or not—for all I know I happened to get sick independently of the drugs this week. Hopefully more experimenters post, as more data is better and if these symptoms are reported by others perhaps causation can be established (or, better, falsified).

No positive changes to report, but that is to be expected given my age (31). I see that there's been an argument concerning use of these drugs by non-aged individuals on this forum. Here's my rationale: clearance of senescent cells in aged and chemotherapy-treated mice has yielded partial rejuvenation. Great. However, in the original study on mice with progeria (now I can't remember if it was from Mayo clinic or Harvard) it was found that clearance of senescent cells from youth prevented appearance of any phenotypic traits of aging whatsoever.
Of course, taking an experimental drug is a huge risk. For personal reasons, I chose to take that risk in full awareness that there may be no positive effects, and that waiting longer might be a more reasonable strategy.

 

I beleive first study is https://www.ncbi.nlm...cles/PMC5296251

and second study is https://www.ncbi.nlm...pubmed/22048312.

[Madfern]

[after injections] Experienced some redness and inflammation around injection site (sub-Q on stomach, left and right of navel), and pain which gradually went away over two days both times. Small lumps now at injection sites—not visible externally, but I can feel them beneath the skin. I was careful with sterility—used bacteriostatic water, needles fresh out of wrapping, clean environment. 

... I became ill with mild flu-like symptoms. ...

 

Thanks for sharing the details of your courageous self-experiment, we can all learn from that.

 

As I see it, there may be a number of issues:

1. Bacteriostatic water is sterile water containing 0.9% benzyl alcohol.  Not the same as phosphate buffered saline (PBS).  The reconstituted solution will not be isotonic, causing hemolysis.  This may explain the lumps you feel.
    
2. The peptide, as supplied, is unlikely to be completely sterile.  Maybe this caused your flu-like symptoms.  A solution is to filter the PBS-reconstituted solution through a 0.22 micron syringe filter.  This will remove all bacteria (but not viruses).  A PES filter membrane might be the best choice to minimize protein binding.
    
3. The container(s) used for reconstituting the solution could contain endotoxins from dead bacteria and therefore be pyrogenic (fever-causing), even if sterile.  Depyrogenation  is difficult.  The best might be to use brand-new, borosilicate glassware and take extreme care with the aseptic technique.

I hope all of your side effects will disappear quickly and that you will get some benefit.

Edited by Manfred B, 08 April 2018 - 09:01 PM.

[chris1299]

Andey, that 2011 paper is the one I was thinking of.

 

Manfred, that is all helpful information. The severity of the side effects (if that's what they are) have been decreasing since the injection. I will update if they persist beyond the next few days, and will update if I seek professional medical advice/treatment.

[OP2040]

Did my 50mg this week, 20mg 4/1 then 30mg on 4/5. Experienced some redness and inflammation around injection site (sub-Q on stomach, left and right of navel), and pain which gradually went away over two days both times. Small lumps now at injection sites—not visible externally, but I can feel them beneath the skin. I was careful with sterility—used bacteriostatic water, needles fresh out of wrapping, clean environment. May have reconstituted with too little fluid.
Both times after injection I became ill with mild flu-like symptoms. Those have mostly subsided by now. Also have been experiencing nausea and constipation. Hard for me to tell if this is just correlation or not—for all I know I happened to get sick independently of the drugs this week. Hopefully more experimenters post, as more data is better and if these symptoms are reported by others perhaps causation can be established (or, better, falsified).

No positive changes to report, but that is to be expected given my age (31). I see that there's been an argument concerning use of these drugs by non-aged individuals on this forum. Here's my rationale: clearance of senescent cells in aged and chemotherapy-treated mice has yielded partial rejuvenation. Great. However, in the original study on mice with progeria (now I can't remember if it was from Mayo clinic or Harvard) it was found that clearance of senescent cells from youth prevented appearance of any phenotypic traits of aging whatsoever.
Of course, taking an experimental drug is a huge risk. For personal reasons, I chose to take that risk in full awareness that there may be no positive effects, and that waiting longer might be a more reasonable strategy.

 

 

I've been one of those that is annoyed by how many young and healthy people are reporting, so let me clarify.  I fully support you and other younger people taking this, and i see the benefits for both you and us.  So I guess my criticism has not so much been against the younger experimenters, as with this really weird dearth of older people.  I really feel like we need older people to be able to judge.

 

Having said that, thanks for providing some great information.  It is flu season still in some areas, I'm just recovering from it myself, so I'm not sure either.  But a lot of this will be clearer with greater numbers of participants.  Eve if the side effects reported so far were due to the substance itself, it would be nothing compared to the potential benefits. 

Edited by OP2040, 08 April 2018 - 09:39 PM.

[Rocket]

I've been one of those that is annoyed by how many young and healthy people are reporting, so let me clarify. I fully support you and other younger people taking this, and i see the benefits for both you and us. So I guess my criticism has not so much been against the younger experimenters, as with this really weird dearth of older people. I really feel like we need older people to be able to judge.

Having said that, thanks for providing some great information. It is flu season still in some areas, I'm just recovering from it myself, so I'm not sure either. But a lot of this will be clearer with greater numbers of participants. Eve if the side effects reported so far were due to the substance itself, it would be nothing compared to the potential benefits.

Do you think so? Honestly you think we need old people to take this and report? No sh*t this "experiment" needs older and preferably middle aged people to participate.

You are people ng to learn ABSOLUTELY NOTHING AT ALL from these people in their 30s taking this peptides! All you're going to learn is whether or not its poison!

The under 40 crowd isn't going to contribute a single thing to this discussion. The over 70 crowd is too far gone for this drug to rejuvenate them. All they MIGHT get from it is some healthier biomarkers in their bloodwork but no one is doing pre and post blood tests....

In short this experiment is going to fail. First of all the dosages are too low. Read one person going to start with 1mg and slowly work up.... By the time they get to a usefu dose their pepetide is going to go sour!

Secondly I understand people worked out the dose by the same conversion of dosages of oral drugs from mice to men.... If true, then WRONG. This isn't aspirin or something that goes through the gut. The dose needs to be scaled up 1:1 with bodyweight. Its injected after all. Doesn't go through the gut. Doesn't go through the liver and then to the rest of the body. It needs to be 1:1 with bodyweight plain and simple!

Ideally this should be by taken by the 40 to 65 subset of the population here on longecity. That's the window of rejuvenation, NOT 30 TO 35!!! You're not going to rejuvenate to 17 because your aging isn't being caused by senescent cells at that young age.

[Rocket]

Oh and one final question, our of curiosity. I am assuming you are younger given your reluctance, so this may not apply to you. But what would you do if reports here started coming in of dramatically good effects and very few side effects? You know as well as I do that this will not reach your doctors office for another 20-30 years probably. Would you wait until you are elderly to take it, just because our system is set up to maximize safety?

You obviously haven't read anything of mine. I am a user of dasatanib which is a senolytic drug tested in people, I can guaranty you I take more anti aging compounds than most people here. The only things IIdont take are NR and c60.

This foxo4 has not even been tried in monkeys. Just ONE mouse study. I know for a fact that there are experimental compounds out there you can buy if you know where to buy fro that cause cancer.

Foxo4 peptides may be a dangerous drug. It might cause liver enzymes to rise and it may affect kidney function and it may do many more harmful things, its never even been studied in monkeys!

What is so hard to understand that you're literally playing Russian roulette by injecting yourself with something some guy sends you in the mail???? For you you 30s people, that is just plain stupid,

You obviously don't know you're preaching to the preacher himself about drug use and experimentation and the absolute joke that we in the USA call the FDA.

The difference is that when I inject myself with what I take, its got studies behind the drug where its been used in humans without causing cancer or liver failure or renal failure... no one here can say one damned word about that foxo4 stuff because its been used in mice one time.

And if you're about 35 and tasking this and expecting to be rejuvenated to your 20s, then you don't even have a grasp on what aging is.

So where are all these brave people with their reports??? Its been in peoples hands for a while and i don't see any before and after pics,...

Edited by Rocket, 11 April 2018 - 02:56 AM.

[Ibbz]

No positive changes to report, but that is to be expected given my age (31). I see that there's been an argument concerning use of these drugs by non-aged individuals on this forum. Here's my rationale: clearance of senescent cells in aged and chemotherapy-treated mice has yielded partial rejuvenation. Great. However, in the original study on mice with progeria (now I can't remember if it was from Mayo clinic or Harvard) it was found that clearance of senescent cells from youth prevented appearance of any phenotypic traits of aging whatsoever.

Of course, taking an experimental drug is a huge risk. For personal reasons, I chose to take that risk in full awareness that there may be no positive effects, and that waiting longer might be a more reasonable strategy.

 

You don't happen to have any sporting injuries that cause you pain or any osteoarthritis like symptoms? (Thanks for the report / results by the way.)

 

 

Patent is pending for FOXO4 DRI as well- 

 

https://patents.goog...0180015137A1/en

[OP2040]

....

 

ok, you seem really passionate (euphemism) about all this.  Let me address your points again, one by one.  And let me say, though your delivery seems a bit hostile, I'm glad you are here as a dissenting voice bringing up very valid points.

 

1. Young people testing this are offering no value.

     * This is the one thing you say that I have to insist is just unequivocally wrong.  You even said yourself several times that

        they will be able to provide information to the rest of us about potential side effects.  some of them also brought up the

        idea that injuries are a perfectly valid testing ground for senescent cell clearance.  I have to agree with them on this

        point. 

     * From what I understand, injuries (even in young people) produce a sizable number of senescent cells and so

        eliminating them is a great test.  The caveat here is that senescent cells are valuable for recent injuries and so the test

        should only be for long term, nagging injuries. 

     * With regard to the accumulation of senescent cells, we simply don't know yet if they are relevant for someone 25-40

        years old.  But we do know that the thymus atrophies relatively early in life, and the immune system plays a role in

        senescent cell clearance.  If that is indeed a significant part of why senescent cells accumulate with age, then it is

        perfectly reasonable to try clearing them at an earlier age.

2. People, particularly young people, are taking a stupid risk supported by very little evidence.

    * I completely agree with this as stated, surprise!

    * Everyone's risk tolerance is different, and I am grateful in some instances for people that take stupid risks.  Jonas Salk

      comes to mind as someone who took a huge risk by taking his own untested vaccine (along with his family).  There was

      no 30 year long clinical trial process, and he saved millions of people from a life of suffering.  Since scientists are not

      even allowed to think about such behavior now (much less act on it) then unfortunately this vacuum needs to be filled

      by much less competent people, myself included.

    * The clinical trial process is important.  But if we rely on it alone, it is very clear that no one on this forum and perhaps no

       one for another hundred years, will actually benefit.  Unity is the only legit company I know of that will go through

       clinical trials for senescent cell removal in the foreseeable future.   Since they aren't allowed to address aging, they are

       going to address osteoarthritic of the knee.  As much as I like this company, the clinical trial won't even start for a

       couple years, and then 30 years from now we MIGHT have a nice therapy for ONE aspect of knee aging.  Then maybe

       some other organ, and perhaps in 200 years we will have some anti-aging for ONE aspect of aging.  The system is

       completely broken for what we want, and therefore we cannot reasonably work within it.  Do you know how long a

       monkey trial takes?  Ya....

    * There are no possible ethical objections to self-experimentation.  We either own our own bodies or we don't.  If we own

       then we are free to do with them what we wish, however stupid it may seem to others.

    * You are great at talking about the huge risks involved.  The most extreme risk here is death to the individual tester.  My

       opinion is that for risk/reward analysis, anti-aging is a special case.  The risk is something that will happen anyway if no

       action is taken, it just may happen at a later date.  The reward is potentially earth shattering.  Is it really a surprise that

       some people will want to take that chance? 

* It's happening, so relax and enjoy the ride.  5-6 people have taken it so far.  None of them have come even close to death,

   so we have to revise the risk side of the equation to what is actually being reported.  No liver/kidney failure, and no

   death.  Then again, how would we know if someone did die.... 

 

I fully share your frustration with the lack of adequate reporting.  Even if people have this stored in their fridge, they should still report in from time to time.  It's probably too much to ask everyone for comprehensive before and after bloodwork, but it's a little selfish to withhold all communication when this should be a highly collaborative effort.

 

Can we have a roll call of FOX04-dri purchasers?
 

[OP2040]

Apologize for the formatting issues....