For those 50 and older, did you run FOX04-DRI ahead of the Mitochondria Repair Stack?

[s2HappyCamper]

When it comes to using FOX04-DRI to clear out senescent cells prior to the NAD+, SSI-31/MOTS-c mitochondrial repair stack, what do you see as the upsides and downsides? Human clinical data for FOX04-DRI is lacking, though animal models and invitro studies do show benefits.

With older individuals, my assumption is that nearly all of them carry a buildup of senescent cells (zombie cells) that release inflammatory signals, harming surrounding healthy cells. So the researcher plans to have RS complete a round of FOX04-DRI. After that FOX04-DRI cycle, should RS hold off for a few weeks before starting the mitochondrial repair stack? Give the apoptosis pathways time to be triggered so those senescent cells die off and get cleared as intended? Any thoughts?

 

[reta-stacker]

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

 

[GLP1Pharmacist]

Based on what I've observed, there isn't much conversation about this, and solid evidence is hard to come by.

 

[Blueeyedme]

This thread might be worth a look. Once I read up on it, I chose not to use FOX04-DRI.

 

[bluewater]

Blueeyedme said:

This thread might be worth a look. Once I read up on it, I chose not to use FOX04-DRI.

Same here. There's some sitting in my freezer now that I doubt I'll ever touch.

My RS is 58, by the way, and did a 12-week run of SS31, MOTS-C and NAD+. The energy increase was incredible.

 

[reta-stacker]

bluewater said:

Blueeyedme said:

This thread might be worth a look. Once I read up on it, I chose not to use FOX04-DRI.

Same here. There's some sitting in my freezer now that I doubt I'll ever touch.

My RS is 58, by the way, and did a 12-week run of SS31, MOTS-C and NAD+. The energy increase was incredible.

Did the RS take them one after another or all at the same time?

 

[bluewater]

NAD kicked off in week 1; SS31 followed in week 2; MOTS arrived in week 3. This staggered approach let me watch for adverse reactions and dial in an effective dose. After that, everything was taken together. I came across plenty of contradictory information on whether SS31 and MOTSC need a specific sequence, or if simultaneous use is acceptable. According to RS experience, running them at the same time works well, with the note that

SS and MOTS both aim at mitochondria, so each got its own separate slot (for example, MOTSC in the morning / SS31 in the evening, or on alternating days). It's a pretty lenient stack.

 

[Researcher6076]

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

If a gray-market product says FOXO4, it is really FOXO4-DRI. No one has ever produced FOXO4 for that market — the name on the label is simply wrong.

 

[Flash-BCR]

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

After coming across this thread, plus a few things I read elsewhere online, I started digging into FOX04-DRI...A purchase I'd been tracking landed today, and I already knew FOX04-DRI would be part of it, but then came the moment the cost showed up: >$300 for a 10mg kit...

My own cutoff, I think, would have sat somewhere around $100-150...but damn. These zombie cells have been riding along with me for this long, so it looks like I'll just keep hauling them around...

 

[Skidude]

Flash-BCR said:

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

After coming across this thread, plus a few things I read elsewhere online, I started digging into FOX04-DRI...A purchase I'd been tracking landed today, and I already knew FOX04-DRI would be part of it, but then came the moment the cost showed up: >$300 for a 10mg kit...

My own cutoff, I think, would have sat somewhere around $100-150...but damn. These zombie cells have been riding along with me for this long, so it looks like I'll just keep hauling them around...

This link also raised a lot of concern

Blueeyedme said:

This thread might be worth a look. Once I read up on it, I chose not to use FOX04-DRI.

FOXO4-DRI



Getting this peptide has been really difficult for me. FOXO4 isn't what I'm after; FOXO4-DRI is, and vendors will tell you anything you want to hear — sure, it's foxo4, or sure, it's foxo4-dri — but not one of them has a CoA. What I do notice is that product code F410 is being sold by multiple vendors...

GLP1Chat.com

 

[Beansnapper]

Researcher6076 said:

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

If a gray-market product says FOXO4, it is really FOXO4-DRI. No one has ever produced FOXO4 for that market — the name on the label is simply wrong.

So what explains the big price gap? I've spotted FOX04 listed around $100, while FOX04-DRI runs $300 to $400. I can't imagine why someone would pick FOX04, though I figure there must be some rationale.

 

[Devilseye]

Beansnapper said:

Researcher6076 said:

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

If a gray-market product says FOXO4, it is really FOXO4-DRI. No one has ever produced FOXO4 for that market — the name on the label is simply wrong.

So what explains the big price gap? I've spotted FOX04 listed around $100, while FOX04-DRI runs $300 to $400. I can't imagine why someone would pick FOX04, though I figure there must be some rationale.

As that other person pointed out, I seriously doubt FOXO4 can be produced without DRI. Without it, the compound would essentially lack potency, effectiveness, or stability.

 

[Devilseye]

By the way, other senolytics such as dasatanib and venetoclax work well when paired with quercetin/fisetin. That's another path I've been considering exploring.

 

[Beansnapper]

Devilseye said:

Beansnapper said:

Researcher6076 said:

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

If a gray-market product says FOXO4, it is really FOXO4-DRI. No one has ever produced FOXO4 for that market — the name on the label is simply wrong.

So what explains the big price gap? I've spotted FOX04 listed around $100, while FOX04-DRI runs $300 to $400. I can't imagine why someone would pick FOX04, though I figure there must be some rationale.

As that other person pointed out, I seriously doubt FOXO4 can be produced without DRI. Without it, the compound would essentially lack potency, effectiveness, or stability.

From what I gather, FOX04 shields senescent cells while Fox04-DRI eliminates them. That's exactly why it makes no sense to me that someone would choose FOX04 at all. Is my take correct?

 

[Devilseye]

Beansnapper said:

Devilseye said:

Beansnapper said:

Researcher6076 said:

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

If a gray-market product says FOXO4, it is really FOXO4-DRI. No one has ever produced FOXO4 for that market — the name on the label is simply wrong.

So what explains the big price gap? I've spotted FOX04 listed around $100, while FOX04-DRI runs $300 to $400. I can't imagine why someone would pick FOX04, though I figure there must be some rationale.

As that other person pointed out, I seriously doubt FOXO4 can be produced without DRI. Without it, the compound would essentially lack potency, effectiveness, or stability.

From what I gather, FOX04 shields senescent cells while Fox04-DRI eliminates them. That's exactly why it makes no sense to me that someone would choose FOX04 at all. Is my take correct?

It's a bit more nuanced than that. In technical terms, the DRI acts as a decoy competitive inhibitor that stops FOXO4 from binding to p53. So it's competing with FOXO4 for p53 binding, but it doesn't really inhibit p53.

But the actual reason standard FOXO4 is useless is that regular FOXO4 is built from L-amino acids, so it gets broken down extremely fast in plasma. Its half-life is only minutes, while DRI is made with non-standard D-amino acids, which gives it a far longer half-life and makes it actually useful.

 

[Researcher6076]

Devilseye said:

Beansnapper said:

Devilseye said:

Beansnapper said:

Researcher6076 said:

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

If a gray-market product says FOXO4, it is really FOXO4-DRI. No one has ever produced FOXO4 for that market — the name on the label is simply wrong.

So what explains the big price gap? I've spotted FOX04 listed around $100, while FOX04-DRI runs $300 to $400. I can't imagine why someone would pick FOX04, though I figure there must be some rationale.

As that other person pointed out, I seriously doubt FOXO4 can be produced without DRI. Without it, the compound would essentially lack potency, effectiveness, or stability.

From what I gather, FOX04 shields senescent cells while Fox04-DRI eliminates them. That's exactly why it makes no sense to me that someone would choose FOX04 at all. Is my take correct?

It's a bit more nuanced than that. In technical terms, the DRI acts as a decoy competitive inhibitor that stops FOXO4 from binding to p53. So it's competing with FOXO4 for p53 binding, but it doesn't really inhibit p53.

But the actual reason standard FOXO4 is useless is that regular FOXO4 is built from L-amino acids, so it gets broken down extremely fast in plasma. Its half-life is only minutes, while DRI is made with non-standard D-amino acids, which gives it a far longer half-life and makes it actually useful.

Additionally, FOX04-DRI carries a tail modification that allows it to cross cell membranes.

 

[Beansnapper]

Devilseye said:

Beansnapper said:

Devilseye said:

Beansnapper said:

Researcher6076 said:

reta-stacker said:

I'm in the same boat as you and wish your question had drawn some replies. I had FOX04 ready to order when it hit me that plain FOX04 actually shields cells, whereas FOX04-DRI is the one that wipes out the zombies — which is presumably the outcome we're after. Sadly, the -DRI version costs a lot, so before I'd bring it in, I'd want to know whether it truly earns a place. Hopefully some folks with more experience can chime in.

If a gray-market product says FOXO4, it is really FOXO4-DRI. No one has ever produced FOXO4 for that market — the name on the label is simply wrong.

So what explains the big price gap? I've spotted FOX04 listed around $100, while FOX04-DRI runs $300 to $400. I can't imagine why someone would pick FOX04, though I figure there must be some rationale.

As that other person pointed out, I seriously doubt FOXO4 can be produced without DRI. Without it, the compound would essentially lack potency, effectiveness, or stability.

From what I gather, FOX04 shields senescent cells while Fox04-DRI eliminates them. That's exactly why it makes no sense to me that someone would choose FOX04 at all. Is my take correct?

It's a bit more nuanced than that. In technical terms, the DRI acts as a decoy competitive inhibitor that stops FOXO4 from binding to p53. So it's competing with FOXO4 for p53 binding, but it doesn't really inhibit p53.

But the actual reason standard FOXO4 is useless is that regular FOXO4 is built from L-amino acids, so it gets broken down extremely fast in plasma. Its half-life is only minutes, while DRI is made with non-standard D-amino acids, which gives it a far longer half-life and makes it actually useful.

After doing some recent reading on these, I can't find any upside to FOX04, even at no cost. I'm aware that FOX04-DRI is not an inexpensive peptide.

Functions of FOXO4​#-functions-of-foxo4

1. Cell Survival: When cells are stressed, FOXO4 assists in shielding them from death. FOXO4 collaborates with other proteins in both healthy and old (senescent) cells to determine if a damaged cell lives or dies.
   
2. Keeping Old Cells Alive: Within senescent cells, FOXO4 binds to p53, a protein that ordinarily signals damaged cells to die. FOXO4 allows these old or damaged cells to persist by blocking p53. Although this may stop immediate cell loss, an excess of old cells can lead to inflammation, tissue issues, and aging-related decline.
   
3. Protection Against Stress: FOXO4 activates genes that assist cells in combating oxidative stress, including antioxidants and DNA repair tools, safeguarding them from damage.
   
4. Energy and Metabolism: It also aids in regulating cell metabolism, blood sugar levels, and energy balance, which supports the overall health of tissues and organs Key Features of FOXO4-DRI
   1. Targets Old Cells: FOXO4-DRI operates by severing the link between FOXO4 and p53 in old (senescent) cells. This releases p53 to initiate cell death in these old cells, while healthy cells remain unaffected.
      
   2. More Stable: The D-Retro-Inverso (DRI) design renders FOXO4-DRI resistant to degradation in the body, so it endures longer and performs better than regular peptides.
      
   3. Anti-Aging Effects: Research in older mice demonstrated that FOXO4-DRI eliminates old cells, rejuvenates tissues, enhances organ function, and increases physical activity, indicating its potential as a treatment targeting aging cells.