848 replies to this topic

[Rocket]

 

 

Well, we don’t really know at this point, there has to be an element of educated guessing. But the study indicated all the reasons why it should be very specific and targeted. It specifically targets only SASP secreting cells. Biology being what it is, there certainly could be some collateral danage. But I’d be most disappointed if it did nothing at all. If it works, alongside some setbacks or concerns, at least we can be sure we’re inching closer to a good therapy for this particular hallmark.



This site can be frustrating, and I'll be the first to admit that I'm going to fall into the "broscience" category because I just don't have the background, or possibly the intelligence, to keep up with some of the more technical discussions.

Having said that, I don't see how eliminating senescent cells is akin to taking cancer meds. There likely won't be many negative side effects from FOX04-dri. The side effects from something like rapamycin are from it's immune compromising effects and not the senolytic action, or so I thought.

The super-healthy 20-30 year old neurotics on here are a huge distraction though. Good for them for being preventative I guess, but it doesn't offer much value to the discussion.

Also, I hope there's another group buy coming up because I'm in!

 

why do you think there will not be likely side effects and various types of normal cells are left alone?

[/quote]

The 20-30 year olds ARE NOT ELIMINATING senescent cells that their immune system would not have cleared regardless.

 

How about a 15 year old? Maybe they should take FOXO4 and be ultra-preventative to acquiring senescent cells.

 

40-45 year sure that's probably fine. But 20 to < 35 is doing nothing but giving themselves negative side effects.

 

Maybe a 2 year old should take FOXO4 every 6 months to prevent them from ever aging.

Edited by Rocket, 22 March 2018 - 07:44 PM.

[meatsauce]

 

The 20-30 year olds ARE NOT ELIMINATING senescent cells that their immune system would not have cleared regardless.

 

How about a 15 year old? Maybe they should take FOXO4 and be ultra-preventative to acquiring senescent cells.

 

40-45 year sure that's probably fine. But 20 to < 35 is doing nothing but giving themselves negative side effects.

 

Maybe a 2 year old should take FOXO4 every 6 months to prevent them from ever aging.

 

 

Reductio ad absurdum

[Ibbz]

 

 

 

Well, we don’t really know at this point, there has to be an element of educated guessing. But the study indicated all the reasons why it should be very specific and targeted. It specifically targets only SASP secreting cells. Biology being what it is, there certainly could be some collateral danage. But I’d be most disappointed if it did nothing at all. If it works, alongside some setbacks or concerns, at least we can be sure we’re inching closer to a good therapy for this particular hallmark.



This site can be frustrating, and I'll be the first to admit that I'm going to fall into the "broscience" category because I just don't have the background, or possibly the intelligence, to keep up with some of the more technical discussions.

Having said that, I don't see how eliminating senescent cells is akin to taking cancer meds. There likely won't be many negative side effects from FOX04-dri. The side effects from something like rapamycin are from it's immune compromising effects and not the senolytic action, or so I thought.

The super-healthy 20-30 year old neurotics on here are a huge distraction though. Good for them for being preventative I guess, but it doesn't offer much value to the discussion.

Also, I hope there's another group buy coming up because I'm in!

 

why do you think there will not be likely side effects and various types of normal cells are left alone?

[/quote]

The 20-30 year olds ARE NOT ELIMINATING senescent cells that their immune system would not have cleared regardless.

 

How about a 15 year old? Maybe they should take FOXO4 and be ultra-preventative to acquiring senescent cells.

 

40-45 year sure that's probably fine. But 20 to < 35 is doing nothing but giving themselves negative side effects.

 

Maybe a 2 year old should take FOXO4 every 6 months to prevent them from ever aging.

 

 

Do you actually have some studies that show senescence build up through human ages? As there's several diseases (E.g. seborrheic dermatitis  https://www.aafp.org.../0701/p125.html ) that do appear once you hit your early 30's - I'm not suggesting senescence is the cause, but obviously something happens by the time adults reach 30 that we start on a downward spiral. I've only found this study (http://www.brown.edu...-06/05-071.html) (which was on baboon's) that shows that senescence was already present by the time they were 5 years old (roughly equivalent to a 15 year old human) and they exponentially build up. 

 

Edited by Ibbz, 22 March 2018 - 10:39 PM.

[Rocket]

Seems to me that by 30, hgh drops dramatically, immune function starts to decline, and wear and tear on shoulders, knees, and spines begin to show up... Things that have VERY little capacity to heal or remodel. Hormones also start their decline by 30. Gene expression begins to change. Glycation begins to accumulate. I can go on and on about changes that happen that don't involve senescent cells.... The newest bogyman.... Causing these changes.

The body has the ability to clear out senescent cells in youth. In middle age is when senescent cells could use help being cleared out.

[Ibbz]

Seems to me that by 30, hgh drops dramatically, immune function starts to decline, and wear and tear on shoulders, knees, and spines begin to show up... Things that have VERY little capacity to heal or remodel. Hormones also start their decline by 30. Gene expression begins to change. Glycation begins to accumulate. I can go on and on about changes that happen that don't involve senescent cells.... The newest bogyman.... Causing these changes.

The body has the ability to clear out senescent cells in youth. In middle age is when senescent cells could use help being cleared out.

 

Regarding "and wear and tear on shoulders, knees, and spines begin to show up" for example, could that not basically be the beginnings of Osteoarthritis (at least for some)? Which studies now suggest that senescence plays a role?

 

https://www.ncbi.nlm...pubmed/28124466

 

"This suggests the hypothesis that senescence of cells within joint tissues may play a pathological role in the causation of OA. In this review, we discuss the mechanisms by which senescent cells may predispose synovial joints to the development and/or progression of OA, as well as touching upon various epigenetic alterations associated with both OA and senescence."

 

or

 

https://academic.oup...2/6/780/2630057

 

"Thus, senescent cells can induce an OA-like state and targeting senescent cells could be a promising strategy for treating OA."

 

For those of us unlucky enough to have issues such as Osteoarthritis, or other problems already at a relatively young age, I think it's definitely worth at least investigating the effect of senescent cell removal.

[stefan_001]

Seems to me that by 30, hgh drops dramatically, immune function starts to decline, and wear and tear on shoulders, knees, and spines begin to show up... Things that have VERY little capacity to heal or remodel. Hormones also start their decline by 30. Gene expression begins to change. Glycation begins to accumulate. I can go on and on about changes that happen that don't involve senescent cells.... The newest bogyman.... Causing these changes.

The body has the ability to clear out senescent cells in youth. In middle age is when senescent cells could use help being cleared out.

 

Hi Rocket, which are the mechanisms that clear out those senescent cells? Would love to read more about that.

[Rocket]

Seems to me that by 30, hgh drops dramatically, immune function starts to decline, and wear and tear on shoulders, knees, and spines begin to show up... Things that have VERY little capacity to heal or remodel. Hormones also start their decline by 30. Gene expression begins to change. Glycation begins to accumulate. I can go on and on about changes that happen that don't involve senescent cells.... The newest bogyman.... Causing these changes.

The body has the ability to clear out senescent cells in youth. In middle age is when senescent cells could use help being cleared out.

Hi Rocket, which are the mechanisms that clear out those senescent cells? Would love to read more about that.

Here is just ONE paper.... Read all about it.

https://www.scienced...568163718300114

[Vantika]

Sorry for not responding earlier.  I've been busy.

 

I have Rheumatoid Arthritis and I get steroid shots in joints every now and then: could that interfere with Foxo4-DRI?

 

Do you think anyone here has done a study on steroid injections and FOXO4? No!

 

Yes!  Corticosteroids (cortisol specifically) have already been directly tested in combination with FOXO4-DRI and shown to negate its effects.

 

It's also been well known for nearly a decade now that corticosteroids (temporarily, partially) inhibit the SASP[3][4].

 

Cortisol's impairing effects on FOXO4-DRI have only been mentioned in this thread about three or four times already. 

 

See my previous posts on this:

http://www.longecity...-12#entry842520

http://www.longecity...-12#entry842569

Some references are included there.   See also [3] and [4].

 

In all probability it would interfere around the sites of injection.  If you want to try to kill senescent cells in those areas, I would recommend abstaining from these injections.

 

FYI, osteoarthritis seems to be primarily caused by cellular senescence[5][6][7][8].

 

If so, how long should I wait after a steroid shot before I can start a course of Foxo4-DRI? 

 

As I mentioned earlier[2], SASP suppression via mTOR inhibition has a particularly long-lasting effect on shutting down the IL1-alpha <-> NF-kB positive feedback loop underlying the inflammatory arm of SASP, by inhibiting translation of IL-1alpha.  This applies to anything inhibiting mTORC1 (e.g. rapamycin, everolimus, a ketogenic diet[9], and probably caloric restriction and intermittent fasting too). 

 

Anything that activates AMPK probably also has some indirect inhibitory effect on mTORC1 and therefore might require a longer wash-out period.  I'll leave it to you to understand the mechanisms of action of your own supplements and to know which, if any, this applies to.

 

Anti-inflammatory compounds/interventions that DO NOT inhibit mTOR shouldn't take nearly as long for any SASP-suppressing effects to subside.

 

Your two week suggestion ought to suffice, I would think.

 

References:

 

[1] http://www.longecity...-12#entry842520

[2] http://www.longecity...-12#entry842569

[3] https://www.ncbi.nlm...pubmed/22404905

[4] https://www.ncbi.nlm...pubmed/19805069

[5] https://www.ncbi.nlm...pubmed/28436958

[6] https://www.ncbi.nlm...pubmed/27516624

[7] https://www.ncbi.nlm...pubmed/28957964

[8] https://www.ncbi.nlm...pubmed/28124466

[9] https://www.ncbi.nlm...pubmed/21371020

 

 

[stefan_001]

 

 

Hi Rocket, which are the mechanisms that clear out those senescent cells? Would love to read more about that.

Here is just ONE paper.... Read all about it.

https://www.scienced...568163718300114

 

 

thanks

 

Edited by stefan_001, 24 March 2018 - 08:14 AM.

[Mind]

Anyone know the fellow in this video (Darren Moore):  He is taking FOXO4 apparently. Same as what is being purchased here?

[jdlancaster519]

Darren Moore, I believe, posted earlier in this thread. I believe he is taking the same substance, but I am not sure from where. 

[stulancs]

Darren Moore is the one from foxo4dri.com that was mentioned a few pages ago. He makes it himself. Had no effect.

[meatsauce]

Darren Moore is the one from foxo4dri.com that was mentioned a few pages ago. He makes it himself. Had no effect.

Not true he doesn't have his own peptide lab.

[Gern]

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.

Edited by Gern, 24 March 2018 - 08:07 PM.

[smithx]

It seems as if doing anything that makes marginal cells more likely to survive would be counter-productive to FOX04-DRI.

So those who are adventurous enough to try it would probably be well-served to spend a few weeks beforehand eating poorly and getting very little exercise.

This is only speculation, and I am not recommending that anyone actually try this.

With regard to Darren Moore and even with regard to this group buy, we have no proof that what they are taking(or what has been purchased here for that matter) is actually the same compound which was used in the published study. So until we can verify that, any results which are posted must be considered very skeptically.

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.

[jdlancaster519]

I, personally, am not too skeptical about the substance bought. Making peptides is a very common thing done by many companies. If I had to independently verify every reagent I put in my lab, it would eat up a lot of grant money and time. If there is a mistake, it is usually with a customer writing down the wrong sequence. I know I did that once with DNA primers... 

[tintinet]

 

 

 

 

Well, we don’t really know at this point, there has to be an element of educated guessing. But the study indicated all the reasons why it should be very specific and targeted. It specifically targets only SASP secreting cells. Biology being what it is, there certainly could be some collateral danage. But I’d be most disappointed if it did nothing at all. If it works, alongside some setbacks or concerns, at least we can be sure we’re inching closer to a good therapy for this particular hallmark.



This site can be frustrating, and I'll be the first to admit that I'm going to fall into the "broscience" category because I just don't have the background, or possibly the intelligence, to keep up with some of the more technical discussions.

Having said that, I don't see how eliminating senescent cells is akin to taking cancer meds. There likely won't be many negative side effects from FOX04-dri. The side effects from something like rapamycin are from it's immune compromising effects and not the senolytic action, or so I thought.

The super-healthy 20-30 year old neurotics on here are a huge distraction though. Good for them for being preventative I guess, but it doesn't offer much value to the discussion.

Also, I hope there's another group buy coming up because I'm in!

 

why do you think there will not be likely side effects and various types of normal cells are left alone?

[/quote]

The 20-30 year olds ARE NOT ELIMINATING senescent cells that their immune system would not have cleared regardless.

 

How about a 15 year old? Maybe they should take FOXO4 and be ultra-preventative to acquiring senescent cells.

 

40-45 year sure that's probably fine. But 20 to < 35 is doing nothing but giving themselves negative side effects.

 

Maybe a 2 year old should take FOXO4 every 6 months to prevent them from ever aging.

 

 

Do you actually have some studies that show senescence build up through human ages? As there's several diseases (E.g. seborrheic dermatitis  https://www.aafp.org.../0701/p125.html ) that do appear once you hit your early 30's - I'm not suggesting senescence is the cause, but obviously something happens by the time adults reach 30 that we start on a downward spiral. I've only found this study (http://www.brown.edu...-06/05-071.html) (which was on baboon's) that shows that senescence was already present by the time they were 5 years old (roughly equivalent to a 15 year old human) and they exponentially build up. 

 

"Seborrheic dermatitis can affect patients from infancy to old age," from your linked article.  I don't see a clear link between senescence and SD.

Edited by tintinet, 28 March 2018 - 09:39 PM.

[Ibbz]

"Seborrheic dermatitis can affect patients from infancy to old age," from your linked article.  I don't see a clear link between senescence and SD.

 

 

Not suggesting there is, just using it as an example of a disease that typically appears from 30 - 60 years of age to illustrate that something has obviously built up enough within the body / or some function within the body is failing by the time you're 30, so people who actually are in there 30's may have a valid reason for trying senescence clearance.

 

"The condition most commonly occurs in infants within the first three months of life and in adults at 30 to 60 years of age."

 

https://www.aafp.org.../0701/p125.html

Edited by Ibbz, 28 March 2018 - 10:17 PM.

[Rocket]

"Seborrheic dermatitis can affect patients from infancy to old age," from your linked article. I don't see a clear link between senescence and SD.

Not suggesting there is, just using it as an example of a disease that typically appears from 30 - 60 years of age to illustrate that something has obviously built up enough within the body / or some function within the body is failing by the time you're 30, so people who actually are in there 30's may have a valid reason for trying senescence clearance.

"The condition most commonly occurs in infants within the first three months of life and in adults at 30 to 60 years of age."

https://www.aafp.org.../0701/p125.html

So because some bad things start around 30, what the hell, lets clear out non-existent senescent cells with medicine with some serious side effects. Yup, perfect logic. What could go wrong? Putting medicine into a perfectly healthy young body...

Lets start people on this at 20 so those bad things don't happen at 30.

Anyone remember Daredevil? The guy used to inject gdf11 as a pick-me-up when he felt sluggish. That's about on par with young people taking medicine to clear out something from their body they don't even have.

Edited by Rocket, 29 March 2018 - 12:39 AM.

[Ibbz]

 

 

"Seborrheic dermatitis can affect patients from infancy to old age," from your linked article. I don't see a clear link between senescence and SD.
 

Not suggesting there is, just using it as an example of a disease that typically appears from 30 - 60 years of age to illustrate that something has obviously built up enough within the body / or some function within the body is failing by the time you're 30, so people who actually are in there 30's may have a valid reason for trying senescence clearance.

"The condition most commonly occurs in infants within the first three months of life and in adults at 30 to 60 years of age."

https://www.aafp.org.../0701/p125.html

So because some bad things start around 30, what the hell, lets clear out non-existent senescent cells with medicine with some serious side effects. Yup, perfect logic. What could go wrong? Putting medicine into a perfectly healthy young body...

Lets start people on this at 20 so those bad things don't happen at 30.

Anyone remember Daredevil? The guy used to inject gdf11 as a pick-me-up when he felt sluggish. That's about on par with young people taking medicine to clear out something from their body they don't even have.

 

 

How about we leave it up to the individual to judge the side effects vs positive effects for themselves? I've just provided several examples of negative effects / diseases that have started occurring by the time someone is in there 30's which may being affecting their life causing them to want to try treatments where there is no established current medical treatment, when you haven't provided any other logical argument against other it than 'they're still young' and they shouldn't do it. I also didn't say people should start this when they're 20 or in their teens.

 

I've also provided a reference to a paper that showed mammalian senescence build up from the equivalent age of 15 years onwards - so its happening in 'young bodies'.

 

Edited by Ibbz, 29 March 2018 - 12:56 AM.

[jdlancaster519]

Senescence also occurs from trauma. So a young person with injuries or other forms of damage (drinking, smoking, disease) will have a build up of senescent cells, but will be specific to the damaged areas. In science experiments they induce a large amount of senescent cells by damaging tissues in young otherwise healthy mice. This could be surgery or damage from a substance. 

 

Here is an article for the layman: https://www.leafscie...osteoarthritis/

 

Here are some scientific journal articles:

https://www.ncbi.nlm...es/PMC4422159/   A direct quote: " Furthermore, although tendinopathy and cell senescence are associated with aging, both may occur at a young age"

 

http://www.cell.com/...5909(16)30456-8

 

Also, a few young experimenters are taking a risk so that others may learn from their experience. Young healthy volunteers are always needed to explore possible side effects.

 

[jdlancaster519]

https://www.ncbi.nlm...les/PMC4422159/

 

first link wasn't working. 

[tintinet]

Initial experience: 30 mg sq EOD x 3. First time injecting- site quite sore for about 18 hours post injection. Sleeping a lot but sometimes still feel tired. I also feel somewhat weak/enervated during workouts. Other times feeling quite good. Possibly all placebo or unrelated to FOXO4.

[Vantika]

First time injecting- site quite sore for about 18 hours post injection.

 

I'm guessing you didn't use PBS.   (Or you didn't use enough of it when reconstituting.)

[tintinet]

 

First time injecting- site quite sore for about 18 hours post injection.

 

I'm guessing you didn't use PBS.   (Or you didn't use enough of it when reconstituting.)

 

Used PBS for sure. Not enough, perhaps.  

[Ibbz]

Ignore post (Please delete moderator)

 

Edited by Ibbz, 30 March 2018 - 10:39 AM.

[Madfern]

Import to Australia:  Has anybody imported FOXO4-DRI to Australia?

Any issues with customs?

How was it declared?

Who was the supplier?

 

I am looking at importing 200mg from Chengdu Youngshe Chemical Co.

They are quoting US$1900 for 200mg.

Has anyone here bought from Youngshe?

 

[OP2040]

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.

[helix66]

Import to Australia:  Has anybody imported FOXO4-DRI to Australia?

Any issues with customs?

How was it declared?

Who was the supplier?

 

I am looking at importing 200mg from Chengdu Youngshe Chemical Co.

They are quoting US$1900 for 200mg.

Has anyone here bought from Youngshe?

 

With the baby food formula deaths in China & and hepatitis outbreaks in Australia from contaminated food items from China, how confident are you about the safety? And if you are confident, what do you base that confidence on?

[Madfern]

 

I am looking at importing 200mg from Chengdu Youngshe Chemical Co.

They are quoting US$1900 for 200mg.

Has anyone here bought from Youngshe?

 

With the baby food formula deaths in China & and hepatitis outbreaks in Australia from contaminated food items from China, how confident are you about the safety? And if you are confident, what do you base that confidence on?

 

 

Youngshe sent me a CoA of a batch from last year.  When I queried the 93% purity result, they sent me a CoA from a more recent batch which showed 98%.

Of course it is possible to forge CoAs or to receive product from an unrelated batch.  But if you don't trust anyone and anything then you probably will die of inaction in the control group.

 

I am planning to have the product tested by LC/MS which would confirm identity based on molecular mass and also give some measure of purity.

Lab services can be found on Science Exchange.

 

To remove bacterial contamination, I'll put the reconstituted solution through a syringe filter (PES, 0.2 micron).

 

I have no idea how to protect against viral contamination -- maybe prophylactically take something like Valacyclovir?

Any suggestions welcome.