Here2Learn
Member
I have Mots-c to research on my list as I’ve heard good things about it too. Just need time to research them all as I try to be pretty thorough.
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RandallFlagg
Member
Definitely good to be through.
There is a general hierarchy for the mitochondrial peptides. The GENERAL thought is to target from top-down such as:
1.) FOXO4-DRI: clear up senescent (dead/inactive) cells.
- Humanin may be one similar in spirit (though think this one might serve more to just improve general cellular stability)
- these are VERY experimental. Not a lot of data...and almost zero human data exists aside for these aside from anecdotal reports.
- the risks are completely unknown and no established protocols (I've done a round of FOXO4-DRI...but would consider your Rapamycin thought to be much safer than my FOXO4-DRI...lol)
2.) SS-31 (there is actually a human drug version of this) - I forget how it works...lol
3.).MOTS-C (so perform step 2 at first at least... thought to make MOTS-c more effective)
Either way,.just some quick brief insight - I didn't pause to look anything up so my info isn't terribly illuminating.
Yeah, but FOXO4-DRI requires intravenous or intraperitoneal administration at this point and as such might not be appealing to users only comfortable with intramuscular or subcutaneous injections.
Letits now
Member
Just finished a course of ss-31/mots. 50 year old male. Got nothing from it. Seems like 50% of people report positive result and the other 50% get nothing from it.
I refer to those two as snake oil peps, but that’s probably not fair. Just don’t work for me.
RandallFlagg
Member
I used it SQ.
Not really a peptide I expected to feel anything with specifically.
Ben Greenfield (ai'ight you can laugh...) is the closest to a reputable source (mostly he experimented with a protocol...but this entire reply puts us closer to sounding like the Reddit rabbit hole). Don't be like me and do drugs kids!
RandallFlagg
Member
Closest I can compare it to is like using GH. Not likely to feel much....but my hope is it improves metabolism. I've read glowing reports from people who claim fabulous energy bursts etc....but other than the GLPs, I'm not sure I can point to a single peptide i believe creates some immediate effect.
I wish more investigation into mitochondrial health would be pursued....(That and someone to finally call out how horrifyingly bad the standard American diet is...and our food is killing us...but yeah,.again I am starting to sound like a ranting Reddit lunatic...lol).
Letits now
Member
I get some of these might be more of a long haul than an immediate result.
I assume there is no money in some of these peps. Or there is no way to patent it? Who knows. Seems like there is potential there but apparently that pharma community doesn’t think so.
I will say that other than glp’s, bpc is the only thing that actually worked for me. Not that I have tried a lot. Bpc really fixed up a chronic shoulder issue I was dealing with for more than a year.
Here2Learn
Member
The mitochondrial stuff is what I am wanting to dive deep into since I have had such amazing success with Thymosin Alpha 1. Thought maybe I should be looking at other areas that need cleaned up and balanced.
Letits now
Member
Is there any kind of before/after testing for the mito stuff? Some kind of non-“feels” proof if you will.
Here2Learn
Member
So I have been reading published research on Mots-c to understand it better. When we exercise it increases Mots-c naturally in our bodies, the younger you are the more you have, which helps build muscle as well as other things. It works in partnership with gut bacteria so I would think if your gut health isn’t good using Mots-c supplements isn’t going to do much for you. I am just beginning the dive into this one but seems there is lot of markers to see if it is helping you.
Here is one study
MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation - PMC
Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c) is a mitochondrial-derived peptide composed of 16 amino acids encoded by the 12S rRNA region of the mitochondrial genome. The MOTS-c protein is transferred to the nucleus during metabolic stress and ...
pmc.ncbi.nlm.nih.gov
MOTS-c stimulates the AMPK pathway which regulates metabolism, fat oxidation, insulin sensitivity and glucose uptake. It also improves mitochondrial biogenesis and nuclear gene expression. MOTS-c also decreases several pro-inflammatory enzymes supporting an anti-inflammatory environment which can actually be beneficial for your gut biome.
One reason most people consider a preparatory course of SS-31 a few weeks to a month before MOTS-c is that SS-31 enables mitochondria to produce more ATP with less ROS production and thus less stress on cellular structures. This makes the MOTS-c course more efficient and productive.
The protocol I use is 4 weeks of SS-31 10mg/day followed by 4 weeks of SS-31 10mg/day and MOTS-c 5mg/day. Then another 4 weeks of MOTS-c at 10mg/day.
To be honest, I don't notice much difference in feels between using the SS-31 or not, but long-term health isn't always indicated with short-term feels.
One reason most people consider a preparatory course of SS-31 a few weeks to a month before MOTS-c is that SS-31 enables mitochondria to produce more ATP with less ROS production and thus less stress on cellular structures. This makes the MOTS-c course more efficient and productive.
The protocol I use is 4 weeks of SS-31 10mg/day followed by 4 weeks of SS-31 10mg/day and MOTS-c 5mg/day. Then another 4 weeks of MOTS-c at 10mg/day.
To be honest, I don't notice much difference in feels between using the SS-31 or not, but long-term health isn't always indicated with short-term feels.
AlexDavis43
Member
Has Ben Greenfield ever said ANYTHING didn't work for him? He always used to only say positive things about everything he tried. Haven't listened in a while though.
I'll go with published studies like the following:
- Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., ... & de Keizer, P. L. J. (2017). Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell, 169(1), 132–147.e16.
- Wu, Y., Shen, S., Shi, Y., Tian, N., Zhou, Y., & Zhang, X. (2022). Senolytics: Eliminating senescent cells and alleviating intervertebral disc degeneration. Frontiers in Bioengineering and Biotechnology, 10, Article 823945. Frontiers | Senolytics: Eliminating Senescent Cells and Alleviating Intervertebral Disc Degeneration
- Zhang, C., Xie, Y., Chen, H., Lv, L., Yao, J., Zhang, M., ... & Liu, G. (2020). FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging, 12(2), 1272–1280. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice | Aging
For a 70kg human, the IP or IV dosage would be ~30mg every third day assuming the same dosing schedule used in animal studies. IM or SC dosages could be expected to be anywhere from 25% to 100% higher due to protease degradation alone. The real problem though comes from the immune response as the FOXO4-DRI would most likely be identified as a foreign body and specific antibodies produced to neutralize its presence. I believe Ghoul has discussed the issue of immune response and GLP-1RAs, and this is in line with his reasoning as well.
I went down this rabbit hole a while back. I'm not comfortable with IV or IP administration at this time and the combination of cost and potential immunological risks of a UGL product makes SC or IM untenable currently. I do look forward to more research.
RandallFlagg
Member
Oh I totally agree...for real. I'm embarrassed to admit I went through the Greenfield phase for a bit a while back. I can't really listen or follow him anymore because he just sounds like a playboy shill.
I only name-dropped him for context that there is close to ZERO human evidence to use FOXO4-DRI. I didn't want to leave the impression I had reams of human data (or any...lol).
RandallFlagg
Member
Thank you for sharing but where did you come up with the human dosing?
I've yet to come across a paper that details any human use. I doubt it exists other than maybe in mother Russia (made that up in my head)...but me and Vlad ain't tight.
Allometric scaling comparing body surface area (BSA) to humans to the test animals (mice).
Mice received 5mg/kg body weight and using BSA normalization factors of 3 for mice and 37 for humans yields ~0.081 as the conversion factor. This makes the human equivalent dose 5mg/kg(mice) * 0.081 = 0.405mg/kg for humans.
RandallFlagg
Member
Yeah, I hear ya and I don't dispute it at all.
Unfortunately, I think the mouse data is just too lower order to extrapolate to humans (just my opinion)...but at least it's something.
Again,.not trying to be a hypocrite..i.ran it SQ for a couple of weeks. I had some of the strangest bloodwork ever in my life just after finishing. I am in the process of waiting for repeat labs to see if it was a real finding or not (literally one doctor said 'this isn't you our blood work...if it is,.you should be dead."...to which I agreed. My PCP said "re-check in 6 months.")
I had already ordered up my own repeat labs because I am virtually certain the lab screwed something up..if not,.there is no chance I'm waiting 6 months to follow up...like wtf.
If for some reason it's repeatable,.I'll follow up in this thread.
RandallFlagg
Member
Alright - short on time but said I would circle back around to this once I had repeat lab work results.
TL;DR: I would suggest extreme caution with FOXO4-DRI until more info comes out.
- I don't know if it was definitively the thing that causes changes or not but it's the only thing I was running differently in between blood checks.
10/26/24: comprehensive lab work checked - very unremarkable aside from LDL to high.
- Creat 1.1 mg/dL
12/16/24: annual check up with PCP -
- Creat 1.57, ALT 68, K 5.2, Ca 11.2, few other parameters off but don't recall (these are all elevated - sorry I'm not posting reference ranges)
- nothing from my doc except "recheck in 6 months" despite never ever having abnormal values in any of these before
- Dropped the FOXO4-DRI (had been doing about 3-6 mg 3x/ week for a few weeks at this point)
- started Telmisartan/Amlodipine (my BP was 132/78...my doc was happy...I'm not)
Re did lab work on my own 12/27/24
- Creat 1.3, Cystatin 1.1 (top end of normal is 1.0)
- ALT 42
- everything else back to normal
Not asking for trouble shooting or I would post more specific comprehensive info.
Mostly throwing out a cautionary tale. I don't know for sure it was the FOXO4-DRI. I'm gonna monitor closer.
I am also probably gonna drop my casual use of 2-4 IU HGH.
I'm not panicked at all but kidneys are not some to mess around with. I' have some thoughts and theories on why I wonder if it's the FOXO4-DRI but for anyone wondering if it's worth making the cost investment, I would advise against it for now.
I also wouldn't argue about whoever posted above about the immunogenicity of SQ administration (and of course Ghouls comprehensive info on this issue).
My urine is negative for protein so I don't think its an autoimmune/glomerular issue. I'll update I future but based on my age and size,.my actual EGFR is > 100 according to the Kidney society calculator (so very normal) but my doctors office numbers said EGFR was 57 (low).
I'm too young to fuck around with the kidneys (but old enough that it probably won't be my life-limiting issue...lol). I'll probably self-refer to a nephrologist if the Cystatin remains high in another month or two but I'll update if anything else points to the FOXO4-DRI in the future.
I just don't want anyone taking my previous casual mention of it as endorsement of safety.
TL;DR: I would suggest extreme caution with FOXO4-DRI until more info comes out.
- I don't know if it was definitively the thing that causes changes or not but it's the only thing I was running differently in between blood checks.
10/26/24: comprehensive lab work checked - very unremarkable aside from LDL to high.
- Creat 1.1 mg/dL
12/16/24: annual check up with PCP -
- Creat 1.57, ALT 68, K 5.2, Ca 11.2, few other parameters off but don't recall (these are all elevated - sorry I'm not posting reference ranges)
- nothing from my doc except "recheck in 6 months" despite never ever having abnormal values in any of these before
- Dropped the FOXO4-DRI (had been doing about 3-6 mg 3x/ week for a few weeks at this point)
- started Telmisartan/Amlodipine (my BP was 132/78...my doc was happy...I'm not)
Re did lab work on my own 12/27/24
- Creat 1.3, Cystatin 1.1 (top end of normal is 1.0)
- ALT 42
- everything else back to normal
Not asking for trouble shooting or I would post more specific comprehensive info.
Mostly throwing out a cautionary tale. I don't know for sure it was the FOXO4-DRI. I'm gonna monitor closer.
I am also probably gonna drop my casual use of 2-4 IU HGH.
I'm not panicked at all but kidneys are not some to mess around with. I' have some thoughts and theories on why I wonder if it's the FOXO4-DRI but for anyone wondering if it's worth making the cost investment, I would advise against it for now.
I also wouldn't argue about whoever posted above about the immunogenicity of SQ administration (and of course Ghouls comprehensive info on this issue).
My urine is negative for protein so I don't think its an autoimmune/glomerular issue. I'll update I future but based on my age and size,.my actual EGFR is > 100 according to the Kidney society calculator (so very normal) but my doctors office numbers said EGFR was 57 (low).
I'm too young to fuck around with the kidneys (but old enough that it probably won't be my life-limiting issue...lol). I'll probably self-refer to a nephrologist if the Cystatin remains high in another month or two but I'll update if anything else points to the FOXO4-DRI in the future.
I just don't want anyone taking my previous casual mention of it as endorsement of safety.
IronWarrior24
New Member
Hey BB69, hit me up on DM, an old time friend trying to get back in touch. Had to make a new profile, my phone got stolen and I've been out of the loop for a while.
You aren't able to dm(I can't send you one either) and I can't leave a msg on your profile either. You're to new.
I think you can pay to upgrade your acct these days? Not sure how much $$ it is? Whatever the cost, trust me, I'm so worth it.
Either that, or I'll wait for you! It shouldn't take that long for you to get those privileges.
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