Just my subjective experience but I have tried BPC157 and several other peptides for healing connective tissue injuries. No change for the injuries but the BPC157 seemed a positive for my digestive track.
FWIW
I have heard about Actovegin from Charles Poliquin(strength and conditioning coach). He said it was great for repairing cartilage and connective tissues. He stated athletes with potential career ending injuries would use it would be like it never occurred. It’s great hear another positive experience about it.
I tried SS-31 at 5 mg/day for 20 days. Just had a renal panel done, which showed no change in any marker, including GFR. Probaly won’t use again.
Currently testing pielotax, a cytomax bioregulator aimed at the kidney. Purchased from CosmicNootropic, a U.S. distributor of Russian products. $115 for a month’s supply of 60 capsules. Arrived in a few days.
Meanwhile, MOTS-C does provide an immediate boost, but I am more interested in what’s going on at the cellular level. The research is excellent. I’ll keep taking this, especially since the protocol is only twice a year.
I’m interested in learning more about this… any reference papers you can share on this topic?
Ah… found one paper, let me know if you know of more:
MOTS-c increases mTORC2 and inhibits PTEN activity, which modulates AKT phosphorylation. Further upstream, MOTS-c increases CK2 activity, which leads to PTEN inhibition. These results suggest that through inhibition of myostatin, MOTS-c could be a potential therapy for insulin resistance-induced skeletal muscle atrophy as well as other muscle wasting phenotypes including sarcopenia.
In the short term, cognitive function enhancement, without side effects, is a major goal for me (especially since the debate…scary). It’s something I can easily assess day to day by how fast I can retrieve things from my memory. It seems to go up and down over the months (like some kind of bio-rhythm…oops, google says “pseudoscience”) and I can’t pinpoint why. I do micro-dose lithium and have experimented with occasional, low dose modafinil. Methylene blue sounds like the first thing I should try and I have this list from you, Charles.
"Ginkgo biloba - Increases blood flow to the brain.
Bacopa monnieri extract. Some studies indicate that it improves memory. It was surprising to me when I first started taking it, it actually started old memories popping up unexpectedly. I really do think it improves the recall of old memories.
Methylene blue. Truly worth a try. It does cross the blood-brain barrier and many studies show that it can improve cognition, plus it has a multitude of other benefits."
Haven’t tried any peptides yet and injections scare me as much as tarantulas but nasal spray, I could handle. Let us know how it works for you.
(I’m thinking of the movie “Limitless”)
Yes! I was having trouble pulling it out of my memory… now, where did I put that pencil…I want to write it down. So, stimulation is all I need? Does porn work?
However, emerging evidence indicates that mTORC2 also has an important role in autophagy, especially mitophagy (the selective degradation of mitochondria by autophagy), as well as a key positive modulator of longevity
From the text at sciencedirect:
Therefore, multiple targets are conceivable for pharmacological rescue of AD and PD symptoms. Protein accumulation can be prevented by stimulating autophagy, e.g. using mTOR inhibitor ([Zhang et al., 2017]… to block endogenous protein seeding for inter-neuronal propagation. MT over-assembly can be prevented by MT disassemblers, such as nocodazole or colchicine …). Combination of the reagents working at different targets could be useful for alleviating symptoms and retarding disease progression. Since synaptic dysfunction and inactivity can secondarily cause neuronal cell damage, blocking such pathological cascades at the early stages of disease seems essential…
Thus: several strategies using small molecules seems to be worth studying more especially for those having high risk for AD or other tauopathies.
https://www.sciencedirect.com/science/article/pii/S0006899324002415?via%3Dihub. gives the composition of the 12-aminoacid peptide and a small helper-peptide(CPP) tagged onto it to promote penetration.
It may take 10-20 years before the pharmaceutical to be developed with this peptide. By that time I will probably be gone and quite some people on this forum too unless miracles happen.
Very sorry for the late reply - just a busy week. Yes, that’s the paper where I first read about mTORC2 also. This is all well outside my wheelhouse, so I’m still reading. I’d like to better understand how MOTS-C acts in contrast to rapamycin with respect to the mTOR complexes, FOXO1 and AKT. Here are things I’ve been reading that touch on that and aging,
Below I also paste GPT-4o’s summary (I have not fact checked GPT’s answer).
GPT-4o:
Rapamycin
mTORC1 and mTORC2:
mTORC1: Rapamycin is well-known for inhibiting mTORC1, which is crucial for muscle protein synthesis. mTORC1 activation involves a cascade of signals from IGF-I, PI3K, PDK1, and Akt, leading to the phosphorylation of downstream targets like 4E-BP1 and p70S6K, enhancing protein synthesis and muscle hypertrophy【source】【source】.
mTORC2: Rapamycin can also affect mTORC2, although its inhibition is less direct and occurs after prolonged exposure. mTORC2 is involved in phosphorylating Akt, which is critical for various cellular functions, including survival and metabolism【source】.
FOXO1:
Rapamycin indirectly impacts FOXO1 through its inhibition of mTORC2. Since mTORC2 phosphorylates Akt, reduced mTORC2 activity leads to lower Akt phosphorylation. This reduction allows FOXO1 to translocate into the nucleus and promote the expression of atrogenes like atrogin-1 and MuRF-1, leading to muscle atrophy【source】.
Akt:
Rapamycin decreases Akt phosphorylation by inhibiting mTORC2. This inhibition affects Akt’s ability to phosphorylate and inhibit TSC2, which normally inhibits mTORC1. Reduced Akt activity thus diminishes protein synthesis and promotes protein degradation pathways【source】【source】.
Myostatin:
Myostatin inhibits muscle growth and its activity can be potentiated by rapamycin through the reduction of mTORC1 activity. Additionally, rapamycin-induced activation of FOXO1 can increase myostatin expression, further promoting muscle atrophy【source】.
MOTS-c
mTORC1 and mTORC2:
mTORC1: MOTS-c indirectly influences mTORC1 by modulating upstream signals that affect Akt activity, although the exact interaction between MOTS-c and mTORC1 isn’t explicitly described in the provided text【source】.
mTORC2: MOTS-c increases mTORC2 activity, enhancing Akt phosphorylation. This increase in Akt activity supports various anabolic processes and cellular survival pathways【source】.
FOXO1:
MOTS-c inhibits FOXO1 activity by promoting its phosphorylation through enhanced Akt activity. Phosphorylated FOXO1 is excluded from the nucleus and targeted for degradation via the ubiquitin-proteasome pathway. This process reduces the expression of muscle atrophy-related genes such as myostatin and atrogin-1【source】.
Akt:
MOTS-c enhances Akt phosphorylation by inhibiting PTEN and increasing CK2 activity, which in turn inhibits PTEN. Elevated Akt phosphorylation (at Thr308 and Ser473) leads to greater Akt activity, which phosphorylates and inhibits FOXO1, reducing muscle atrophy signals【source】.
Myostatin:
MOTS-c reduces myostatin expression by inhibiting FOXO1 activity. Since FOXO1 can upregulate myostatin transcription, its inhibition by MOTS-c decreases myostatin levels, promoting muscle growth and combating muscle wasting conditions【source】.
Comparison and Contrast
Rapamycin inhibits mTORC1 directly and mTORC2 indirectly, leading to reduced Akt activity and increased FOXO1 activity, which promotes muscle atrophy and increases myostatin expression.
MOTS-c increases mTORC2 activity, leading to enhanced Akt phosphorylation. This activity results in the inhibition of FOXO1, reducing myostatin levels and preventing muscle atrophy.
In summary, while rapamycin tends to promote muscle atrophy through the inhibition of mTOR pathways and activation of FOXO1, MOTS-c works oppositely by enhancing Akt activity, inhibiting FOXO1, and thus supporting muscle maintenance and growth.
The review article mentioned below left me stunned about the complexity of the workings of mTor. The graphs give some clarity and may be a source for some items asked in previous post.
Ragopathies and the rising influence of RagGTPases on human diseases Nature Communicationsvolume 15, Article number: 5812 (2024)
Hi dessertstorm and Tim, thank you both for all the information on getting the peptides ophthalmic for my eyes. I am pleased to say that they arrived last week and I will now start the protocol. Should there be any miraculous changes? I will definitely let you know. Thank you again.
Dee
