SS-31 protocols?

chmuse said:
If you get the chance, look at the threads the vendor has posted in. Lots of info if you read the entire threads.
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Ok thanks for the reply, I think I misspoke. my question should have been: Has any group/person ever tested Nexaph's product independently/on their own?
 
Fisherman2356 said:
Ok thanks for the reply, I think I misspoke. my question should have been: Has any group/person ever tested Nexaph's product independently/on their own?
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Yes, most of his products get tested third party after the fact. There's an entire telegram for it.
 
Trial dosages are in the range of 20mg (low dose trials)-40mg/day sub-q. Based on that, there's no reason to think less than 1mg/day is going to do literally anything besides give your an occasional bruise from the injection. Here's an example for dry eye age related macular dysfunction. https://clinicaltrials.gov/study/NCT06373731?intr=Elamipretide&rank=4

This is a peptide where human clinical trial data actually exists. 500mcg is pointless.
 
lazygardener said:
Trial dosages are in the range of 20mg (low dose trials)-40mg/day sub-q. Based on that, there's no reason to think less than 1mg/day is going to do literally anything besides give your an occasional bruise from the injection. Here's an example for dry eye age related macular dysfunction. https://clinicaltrials.gov/study/NCT06373731?intr=Elamipretide&rank=4

This is a peptide where human clinical trial data actually exists. 500mcg is pointless.
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Placebo effect is a hell of a drug.
 
lazygardener said:
Trial dosages are in the range of 20mg (low dose trials)-40mg/day sub-q. Based on that, there's no reason to think less than 1mg/day is going to do literally anything besides give your an occasional bruise from the injection. Here's an example for dry eye age related macular dysfunction. https://clinicaltrials.gov/study/NCT06373731?intr=Elamipretide&rank=4

This is a peptide where human clinical trial data actually exists. 500mcg is pointless.
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40mg/daily was also used for the mito clinical trial. https://pmc.ncbi.nlm.nih.gov/articles/PMC10382259/ Prohibitively expensive at current prices.
 
After looking at many different options my first cycle was 4mg 5days on 2 days off for 6 weeks.
I am now ready for my next and will be stacking with overlaps as well- SS-31, Mots-C, NAD+
This is my current SS-31 protocol- Going with Basic first. 5mg a day also taking CoQ10,TMG,Lipo-c w/b12

Basic SS-31 Cycle (General Health & Mitochondrial Support)
Dosage: 5-10 mg subcutaneous (SQ) daily
Duration: 6-8 weeks
Break Between Cycles: 6-8 weeks off
Considerations:
Take on an empty stomach for better mitochondrial uptake.
Pair with Lipo-C, B12, or CoQ10 for enhanced mitochondrial function.
Combine with low-impact exercise (walking, bodyweight training) for best results.
Advanced SS-31 Cycle (Athletic Recovery & Performance)
Dosage: 10-20 mg SQ daily
Duration: 8-12 weeks
Break Between Cycles: Equal to cycle length (8-12 weeks)
Additional Support:
Lipo-C/B12 injections for metabolism & energy.
Creatine, TMG, and CoQ10 for added mitochondrial support.
Cold therapy or sauna use to enhance mitochondrial function.
Optional: Microdosing Approach (for Longevity & Maintenance)
Dosage: 5 mg SQ 3-4x per week
Duration: Ongoing with periodic breaks
Breaks: 2-4 weeks off every 3 months
 
Skidude said:
After looking at many different options my first cycle was 4mg 5days on 2 days off for 6 weeks.
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Thanks for the info. More info on your first cycle:

Skidude

Post in thread 'I'm going to shoot for losing 100 pounds in 6 months'

raw_oyster_eater said:
i'm gonna keep up with the ss31. people say it helps take weight off. one thing besides glp1 at a time.
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I tried the 4mg daily, 5day on 2day off, protocol then stack mots after 4 weeks. continue for a few weeks with both. I did add the TMG. I am not big on feels, more like gradual changes, but am tempted to try to cycle up on next pass. just very costly vs other stacks. My energy was very low as a result f tirz and very low calorie I assume, it seems to have provided a boost. I have steadily dropped 1.5lbs per week over the last 7-8 weeks on cycle. But am considering the...
Skidude

Post in thread 'Did you ever feel like you knew everyone on a TV show?'

raw_oyster_eater said:
that's good information thank you.

what do you think of ss31? i have a kit and i'm itching to do it.
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It is tough to say, I am hoping it is helping with the mots etc.. not a huge "feel" for me, but i did notice some increased energy, which on 1200 calories is much needed. I also hope it helps with the Mots-c efficacy. I have been taking TMG supplement to help with those as well.
Overall any effects would be positive, and worth the first cycle for sure.. IMHO
 
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Calm Logic said:
Thanks for the info. More info on your first cycle:

Skidude

Post in thread 'I'm going to shoot for losing 100 pounds in 6 months'

raw_oyster_eater said:
i'm gonna keep up with the ss31. people say it helps take weight off. one thing besides glp1 at a time.
Click to expand...
I tried the 4mg daily, 5day on 2day off, protocol then stack mots after 4 weeks. continue for a few weeks with both. I did add the TMG. I am not big on feels, more like gradual changes, but am tempted to try to cycle up on next pass. just very costly vs other stacks. My energy was very low as a result f tirz and very low calorie I assume, it seems to have provided a boost. I have steadily dropped 1.5lbs per week over the last 7-8 weeks on cycle. But am considering the...
Skidude

Post in thread 'Did you ever feel like you knew everyone on a TV show?'

raw_oyster_eater said:
that's good information thank you.

what do you think of ss31? i have a kit and i'm itching to do it.
Click to expand...
It is tough to say, I am hoping it is helping with the mots etc.. not a huge "feel" for me, but i did notice some increased energy, which on 1200 calories is much needed. I also hope it helps with the Mots-c efficacy. I have been taking TMG supplement to help with those as well.
Overall any effects would be positive, and worth the first cycle for sure.. IMHO
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I am far from an expert on any of this, and most of the time blindly trying to find my way in the dark, but I do believe this is like many other supplements/peps/meds in that it is very specific to individual physiology.
If a person with ADHD takes Adderall it calms them down, it has a very different effect if you do not.
Same with B12 deficiency, and many other related issues.
This makes it hard to pinpoint what is working- And makes all of this anecdotal IMHO.

Elamipretide (SS-31), a synthetic tetrapeptide, is being investigated for its potential to help individuals with damaged mitochondria. SS-31 is designed to selectively target mitochondria, aiming to restore their function, particularly in conditions like mitochondrial diseases and aging.

Maybe my body needed ss-31 to help other peps work, maybe it did not.
Perhaps it is just a motivation to improve that is the real "pep" in my step.
I may never know.

For now, I am happy with the Red pill or the Blue pill, the steak is delicious, albeit much smaller than it used to be.
 
Yeah, I'm mostly interested in the info for a relative with mild/moderate chronic kidney disease. But the ideal, more experimental dosing is very expensive. So I see it more as an add-on to the more affordable BPC-157, which may also help with CKD.

The Mitochondrion: A Promising Target for Kidney Disease - PMC

Mitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov

Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy - PubMed

Oxidative stress is implicated in the pathogenesis of diabetic kidney injury. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge reactive oxygen species (ROS). Here, we investigated the effect and molecular mechanism of mitochondria-targeted antioxidant peptide SS-31 on injuries in...
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

I think what may help the most about this research is finding cheap supplements that would help with similar pathways. Supplements such as MitoQ, CoQ10, Alpha-Lipoic Acid (ALA), N-Acetylcysteine (NAC), L-Carnitine, Resveratrol, Green Tea Polyphenols (EGCG), and Curcumin/Tumeric.

More info on SS-31 for CKD:

Google Gemini said:
SS-31, a mitochondria-targeting peptide, has shown promise in ameliorating kidney disease, including Chronic Kidney Disease (CKD). Several studies suggest it can:
  • Improve kidney function: By lowering urinary albumin excretion, proteinuria, serum creatinine, and BUN.

  • Protect against oxidative stress: SS-31 can reduce reactive oxygen species (ROS) production, preventing damage to renal cells.

  • Reduce inflammation: It can inhibit the production of pro-inflammatory cytokines.

  • Prevent mitochondrial dysfunction: SS-31 protects mitochondrial structure and function, which is crucial in kidney health.

  • Protect podocytes: SS-31 has shown protective effects on podocytes, cells vital for kidney function, in diabetic kidney disease models.
However, it's important to note that while preclinical studies and some clinical trials show positive results, further research is needed to confirm these findings and establish the long-term effectiveness and safety of SS-31 for CKD. Some studies also indicate that the effectiveness of SS-31 can vary depending on the specific cause and model of kidney injury.
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Skidude said:
For now, I am happy with the Red pill or the Blue pill, the steak is delicious, albeit much smaller than it used to be.
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I feel ya. I've been on 5mg daily for 11 days. Starting Mots-c on day 14. 5mg daily with two days off (3/2). Ss-31 will probably always be part of the rotation since I have felt some energy and focus gains.
 
Peloma said:
I feel ya. I've been on 5mg daily for 11 days. Starting Mots-c on day 14. 5mg daily with two days off (3/2). Ss-31 will probably always be part of the rotation since I have felt some energy and focus gains.
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I may have plagiarized your "pep in the step" when writing.. lol
 
Skidude said:
Elamipretide (SS-31), a synthetic tetrapeptide, is being investigated for its potential to help individuals with damaged mitochondria. SS-31 is designed to selectively target mitochondria, aiming to restore their function, particularly in conditions like mitochondrial diseases and aging.
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Thanks again. I just started reading about SS-31 a week ago. I didn't know that Elamipretide was the name for it, or that its peptide class is tetrapeptide.
 
lazygardener said:
Trial dosages are in the range of 20mg (low dose trials)-40mg/day sub-q. Based on that, there's no reason to think less than 1mg/day is going to do literally anything besides give your an occasional bruise from the injection. Here's an example for dry eye age related macular dysfunction. https://clinicaltrials.gov/study/NCT06373731?intr=Elamipretide&rank=4

This is a peptide where human clinical trial data actually exists. 500mcg is pointless.
Click to expand...

Similarly, from another study by the same company, SS-31 was well-tolerated at 40mg/day (though not effective for a rare disorder):

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial - PMC

Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
2023 Jul 18
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After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide [SS-31] at a dose of 40 mg/d or placebo subcutaneously...

Subcutaneous elamipretide treatment did not improve outcomes in the 6MWT [Six-Minute Walk Test] and PMMSA TFS [Primary Mitochondrial Myopathy Symptom Assessment Total Fatigue Score] in patients with PMM [primary mitochondrial myopathy]. However, this phase-3 study demonstrated that subcutaneous elamipretide [SS-31] is well-tolerated.
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From a small study (PDF) using rats:

"Our data show the potential of SS-31 as a novel therapeutic in cardiac arrest"

"Previous studies tested SS-31 using different dosages invarious diseases [3] and 0.05mg/kg/h is a commonly used dosage for continuous administration with consistent effectiveness"

"Mitochondrial dysfunction is believed to play an important role for the pathogenesis of cardiac arrest."

"The wide spectrum of protective action makes SS-31 a promising therapeutic agent in CA [cardiac arrest], where multiple organs are affected."
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RubiJeep_Girl said:
I tried MOTSc for about two weeks but didn't have any increased energy or anything. Then I realized I should have started with SS-31 first to prime my system so to speak so I stopped it LOL..... That's around the same time of my Tirz stall aka its never really worked for me.

So I came up with the plan to do a cycle of NAD & AOD between cycling off the Tirz. I do notice increased energy with the NAD+ as well, I was impressed since I've never had consistent responses from Sema or TIrz, FINALLY something my body is working with.

I'll start Reta January first, as long as I make it that long. Then I'll drop the AOD mid January and start the SS31, followed by the MOTSc....... I'll need a calendar to keep these things straight lol
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I was told that you use as-31 first, then MOTS-C, because the first one heals and optimizes, but I don’t know if it’s true.
 
I think most are quoting Dr. Seeds protocol, although I have not been able to confirm, it is certainly my motivating reason to buy into ss-31 then mots.
From his book:
1745229650112.png


William A. Seeds, MD is a board-certified surgeon practicing medicine for over 30 years. He is Founder and Chairman of the International Peptide Society, Faculty Developer and Lecturer of the A4M Peptide Certification Program, and a leading peptide therapy researcher. He is Chief of Surgery and Orthopedic Residency Site Director for University Hospital, Conneaut, and Medical Director of Orthopedic Rehab and Sports Medicine at the Spire Institute, a USA Olympic training site. Dr. Seeds has been honored at the NFL Hall of Fame for his medical expertise and in treating professional athletes, and serves as Professional Medical Consultant for the NHL, MBL,NBA, and NBC’s Dancing with The Stars.

seeds.md

Dr. William Seeds | Seeds.md

This is the homepage for William A. Seeds MD, Board Certified Orthopedic Surgeon, Residency Site Director for University Hospital in Geneva and Conneaut OH, and the Founder of the Seeds Scientific Research and Performance (SSRP) Institute, a medical education and certification program for...
seeds.md seeds.md

HERE is one of his podcast interviews, many more links on youtube.



HERE is another example from a random user I found:
It’s a matter of mitochondrial genomics and their ability to self replicate (only other self replicating organelle I can think of are peroxisomes in animals).

Remember: The mitochondrial membrane have the proteins responsible for the cell to produce “energy” and “breathe” for the cell — the electron transport system. So a partially denatured and damaged membrane of mitochondria (phospholipid cardiolipin) make it harder for the cell to do its normal function, producing proteins, etc…leading to be harder for tissues and organs to function properly and the body being tired and lack ability to properly function.

Mitochondria are self replicating. If one has mitochondrial breakdown of membranes due to ROS — reactive oxygen species — free radicals…at any point mutations (or others) in the mitochondrial genome is likely to reproduce/self-replicate mitochondria with those same mutations (F1 generation).

Furthermore, like any other genome or organism — remember though it is the mitochondria is an organelle — and, it is subject to both epigenetics and pleiotopy. If the mitochondria are exposed to ROS, these ROS have an effect on gene expression resulting in possible mitochondria expressing genes (phenotypes) that underwent mutation. Pleiotropy — if an affected mitochondria results in mutations prior to self replication, and if gene is pleiotropic (but consider all genes are pleiotropic to some degree) that has expression of that mutation will result in many phenotypic changes that are deleterious in the normal functioning of that mitochondria and hence likely the entire cell.

Therefore, healing properties of SS-31 will have a greater effect on mitochondrial function within cells and (theoretically) other peptides will be more effectual in helping the body.

This an oversimplified description of genetics of mitochondria or the cell itself.

Main point— SS31 or Humarin (HGN) should come before MOTS-C which directly stimulates the present mitochondria (at time of use ) to performing better.

I mentioned peroxisomes notable function is to “neutralize” reactive oxygen species in the cell or detox the cell of free radicals. Also they are involved in metabolism (catabolism) of fatty acids in the cells. Due to the structure of fatty acids— they are hydrogen rich — the hydrogen density exposes them to reactive oxygen species. I am not aware of any peptide that helps peroxisomes function better.
 
I just read the Peptide Protocols book and there is no mention of SS-31, so it must be something that either came up at a later date (after 2020) or that is being attributed to him inaccurately.
It does seem to be supported by his assessment of cell protection/optimization theory, in my layman's understanding.
Full disclosure, I had to google a lot of terms...
 
From Goodkitty at Peppys:

For the SS31 and the MOTS C - since they are more mitochondrial - I didn’t’ expect to have any “feels” but hope to see improvements on followup mitochondrial/telomere/aging testing when I have it redone.
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So with that perspective, I found this:

Telomeres and Mitochondrial Function - PMC

pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

A new study provides insight into aging and age-related diseases by linking telomere dysfunction to a decline in mitochondrial number and function.
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Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-related Diseases - PMC

Cellular senescence is an irreversible cell arrest process, which is determined by a variety of complicated mechanisms, including telomere attrition, mitochondrial dysfunction, metabolic disorders, loss of protein homeostasis, epigenetic changes, ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov

Cellular senescence is an irreversible cell arrest process, which is determined by a variety of complicated mechanisms, including telomere attrition, mitochondrial dysfunction, metabolic disorders, loss of protein homeostasis, epigenetic changes, etc. Cellular senescence is causally related to the occurrence and development of age-related disease...More and more evidences have shown that there is mutual crosstalk between telomeres and mitochondrial metabolism in the process of cellular senescence.
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Playing with Google Gemini regarding oral supplements vs SS-31:

While many oral supplements for mitochondrial health aim to support overall mitochondrial function, very few are specifically designed to target the inner mitochondrial membrane in the same way that SS-31 does.

Here's a breakdown of why and some potential exceptions or related concepts:

Why Direct Targeting is Difficult for Oral Supplements:
  • Absorption and Distribution: Oral supplements go through the digestive system, are absorbed into the bloodstream, and then distributed throughout the body. Achieving a high concentration specifically within the inner mitochondrial membrane from an oral dose is a significant challenge.

  • Cellular Uptake: Even if a supplement reaches cells, it needs specific mechanisms to cross the cell membrane and then the outer and inner mitochondrial membranes.

  • Targeting Mechanisms: SS-31's effectiveness in targeting the inner mitochondrial membrane relies on its specific affinity for cardiolipin, a unique phospholipid found almost exclusively in that location. Most oral supplements lack such a precise targeting mechanism.
However, some oral supplements or their components may indirectly benefit or interact with the inner mitochondrial membrane:

  • Antioxidants: Certain antioxidants like CoQ10 (ubiquinol) and alpha-lipoic acid can accumulate within mitochondria to some extent and help reduce oxidative stress in both the inner and outer membranes, as well as the matrix. While they don't have a specific targeting mechanism like SS-31, their lipophilic nature allows them to integrate into mitochondrial membranes.

  • Phospholipid Precursors: Some supplements contain phospholipids like phosphatidylcholine or precursors to cardiolipin. While not directly targeted, providing the building blocks for mitochondrial membranes can support their structure and function, including the inner membrane.

  • MitoQ: This is a mitochondria-targeted antioxidant that combines ubiquinone (a form of CoQ10) with a lipophilic triphenylphosphonium (TPP+) cation. The TPP+ helps it to be taken up by mitochondria due to the negative charge of the mitochondrial membrane potential. While MitoQ has shown promise, it's not always available as a standard oral supplement and its targeting mechanism isn't solely specific to the inner membrane, but rather the entire mitochondrial matrix.

  • Urolithin A: This postbiotic metabolite can promote mitophagy, the selective removal of damaged mitochondria, which indirectly supports the health of the remaining mitochondria, including their inner membranes.
In summary:

While many oral supplements provide nutrients that are crucial for overall mitochondrial health and can exert beneficial effects within the mitochondria (including the inner membrane), they generally lack the specific cardiolipin-targeting mechanism of SS-31. Some antioxidants and phospholipid precursors in oral supplements can integrate into or support the inner mitochondrial membrane, but their action is less directly targeted compared to compounds like SS-31 or MitoQ.

The development of truly targeted oral supplements for the inner mitochondrial membrane remains an area of ongoing research.
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Peptides with Potential Telomere-Related Effects (Primarily Research):

  • TA-65: While often available orally, TA-65 is a purified small molecule derived from Astragalus membranaceus that has shown some evidence of activating telomerase, the enzyme that can lengthen telomeres. There have been injectable formulations used in research settings, but it's not a widely available injectable supplement for the general public.

  • Epitalon (Ala-Glu-Asp-Gly): This synthetic tetrapeptide is a more well-known research peptide with potential anti-aging effects. Studies have suggested it can increase telomerase activity and lengthen telomeres in some cell types and animal models. It is available through some specialized pharmacies and research suppliers as an injectable, but its widespread use and regulatory status vary significantly. Human clinical trial data on its efficacy and safety for telomere lengthening is still limited.

  • MOTS-c (Mitochondria-Derived Peptide):While primarily known for its role in metabolic regulation and exercise mimicry, MOTS-c has shown some potential links to cellular longevity and mitochondrial health. Given the close relationship between mitochondrial dysfunction and telomere shortening, supporting mitochondrial health through MOTS-c might indirectly benefit telomeres. Injectable forms are mainly used in research.

  • SS-31 (Elamipretide):As we've discussed, SS-31 targets the inner mitochondrial membrane and reduces oxidative stress. While its primary mechanism isn't direct telomere lengthening, its potent antioxidant effects within mitochondria could help protect against oxidative damage that contributes to telomere shortening. Injectable formulations are used in research and some clinical trials for other indications.
Other Injectable Considerations (Less Direct Telomere Focus):

  • Certain Antioxidants (e.g., Glutathione, Vitamin C): While available in injectable forms, their primary role is to combat oxidative stress. By reducing cellular damage, they might indirectly help preserve telomere length, but they don't directly target telomeres.
  • Growth Hormone (GH) and Growth Hormone-Releasing Peptides (GHRPs): These can have various effects on cellular function and might influence aging processes, but their direct impact on telomere length is complex and not well-established as a primary benefit for preventing telomere shortening.
  • TA-65: While often available orally, TA-65 is a purified small molecule derived from Astragalus membranaceus that has shown some evidence of activating telomerase, the enzyme that can lengthen telomeres. There have been injectable formulations used in research settings, but it's not a widely available injectable supplement for the general public.

  • Epitalon (Ala-Glu-Asp-Gly): This synthetic tetrapeptide is a more well-known research peptide with potential anti-aging effects. Studies have suggested it can increase telomerase activity and lengthen telomeres in some cell types and animal models. It is available through some specialized pharmacies and research suppliers as an injectable, but its widespread use and regulatory status vary significantly. Human clinical trial data on its efficacy and safety for telomere lengthening is still limited.

  • MOTS-c (Mitochondria-Derived Peptide):While primarily known for its role in metabolic regulation and exercise mimicry, MOTS-c has shown some potential links to cellular longevity and mitochondrial health. Given the close relationship between mitochondrial dysfunction and telomere shortening, supporting mitochondrial health through MOTS-c might indirectly benefit telomeres. Injectable forms are mainly used in research.

  • SS-31 (Elamipretide):As we've discussed, SS-31 targets the inner mitochondrial membrane and reduces oxidative stress. While its primary mechanism isn't direct telomere lengthening, its potent antioxidant effects within mitochondria could help protect against oxidative damage that contributes to telomere shortening. Injectable formulations are used in research and some clinical trials for other indications.
Other Injectable Considerations (Less Direct Telomere Focus):

  • Certain Antioxidants (e.g., Glutathione, Vitamin C): While available in injectable forms, their primary role is to combat oxidative stress. By reducing cellular damage, they might indirectly help preserve telomere length, but they don't directly target telomeres.
  • Growth Hormone (GH) and Growth Hormone-Releasing Peptides (GHRPs): These can have various effects on cellular function and might influence aging processes, but their direct impact on telomere length is complex and not well-established as a primary benefit for preventing telomere shortening.
Click to expand...
 
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The premise, as I understand it, of Seeds peptide book is homeostasis- the ability of the body to fix itself (my very basic description).

The relationship of cells and how they affect us as a whole.

He discusses Senescence in detail as well as telomere

From his book:
Cell Senescence Cell senescence was first discovered in the 1960s by Hayflick and Moorhead, who observed a number of cells that simply stopped dividing— they neither grew and divided nor progressed to cell death—these cells were arrested. This phenomenon changed our understanding of the cell cycle. Hayflick and Moorhead went on to define cell senescence as an indication of a cell’s biological clock; they called it the Hayflick limit. At the time, the cell arrest of senescence was attributed to a progressive shortening of telomeres with each cell division. They understood this telomere erosion to be part of a physiological response to prevent genomic instability and DNA damage. Now we know that cell senescence is much more complicated.
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So how and why does senescence occur? Senescence can be triggered by various mechanisms, through multiple pathways: Gradual erosion of telomeres, triggering a DNA damage response in the genome of the mitochondria Chronic physiological stress, including bad diet, lack of exercise, and stubborn insult to glucose metabolism. Downstream of senescence brought on by physiological stress, you will find oxidative stress, endoplasmic reticulum stress (resulting in unfolded protein response or UPR),mitochondrial stress (cytoplasmic chromatin fragments, or CCFs), and interferon-related responses. Acute injury or trauma to any area of the brain or body (anything from osteoarthritis in a knee to a TBI) As a result of anti-cancer treatments (radiation and chemotherapy) that purposely bring cell senescent onset; this is often referred to as therapyinduced senescence. Finally, senescence is the result of a systemic proinflammatory state, which has driven the immune system into hyper mode, degrading its ability to maintain homeostasis cellular protection. Essentially, any of these senescence inducers are a form of stress on the cell and its systems. Yes, the cell requires stress to nudge it into its cell cycle. However, when any one or more of these stressors overwhelms the cell—in either their degree or their chronic-ness—the cell’s ability to adapt becomes undermined. Cellular senescence is even more dangerous because it not only affects an individual cell, but it also affects nearby and distant tissue through chronic inflammatory response, reactive oxygen species, and insufficient apoptosis. The bottom line is that the characteristics of the senescent cell—in particular its secretory phenotype—diminish its resistance to diseasecausing stressors and cause stem and parenchymal cell dysfunction. (Indeed, stem cells are particularly vulnerable to damage from SASP because of the harmful effect on their microenvironment, or niche.
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2 days ago, I added methylene blue to the stack. I know... I fell victim to the hype. Let me tell you, it's legit! The methylene blue gives an extra boost to my energy, and pairs really well with my SS-31. I have more focus and energy this morning than on SS-31 alone, and knowing that the SS-31 is in the background repairing mitochondria while the blue moves electrons to needed parts in my cells is a great feeling.

Downside was with sleep... didn't get much. I'm sure it will adjust as I acclimate.
 
Cool. I know my local compounding pharmacist is promoting methylene blue like crazy, so I guess I will try it now.

Regarding Dr. Seeds and cell signaling, I see this is what he says about GLP-1s:

www.ihsymposium.com

Rewriting Metabolic Destiny: GLP-1R Agonists as the Natural Key to Cellular Efficiency and Epigenetic Renewal | Integrative Healthcare Symposium

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), mimicking our body's natural incretin hormones, have transformed metabolic disorder management. Beyond their known efficacy in blood sugar control and weight loss, emerging research...
www.ihsymposium.com www.ihsymposium.com

Key takeaway points include:

– GLP-1 receptor agonists (GLP-1 RAs) have multifaceted effects beyond glucose control and weight loss, influencing multiple cellular pathways crucial for metabolic health and longevity.

– GLP-1 RAs modulate key signaling pathways such as insulin signaling, mTOR, AMPK, Nrf-2, sirtuin activity, and NAD⁺ metabolism, leading to enhanced mitochondrial function, energy balance, and reduced oxidative stress.

– GLP-1 RAs exhibit anti-inflammatory and senomodulatory properties, impacting immune cell polarization, promoting positive epigenetic modifications, and influencing cellular senescence, which may reverse harmful changes associated with chronic metabolic diseases, aging, and cancer.
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Calm Logic said:
Cool. I know my local compounding pharmacist is promoting methylene blue like crazy, so I guess I will try it now.

Regarding Dr. Seeds and cell signaling, I see this is what he says about GLP-1s:
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Let me know when you do. We can compare notes. I've taken 20 drops (.5mg/drop = 10mg) Sunday, yesterday morning and this morning. Last night I dropped 40 drops (20mg), and I really felt it, but that's also probably why I couldn't sleep. Tonight it will be 20 drops again to total my daily dose at 20mg.
 
Peloma said:
Let me know when you do. We can compare notes. I've taken 20 drops (.5mg/drop = 10mg) Sunday, yesterday morning and this morning. Last night I dropped 40 drops (20mg), and I really felt it, but that's also probably why I couldn't sleep. Tonight it will be 20 drops again to total my daily dose at 20mg.
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What brand is yours?
 
Biopharm straight off Amazon. It was well priced abd tested. I may go with the pills going forward because this liquid tastes like shit.
 
You could always mix it with tuna juice like people do for medicating their cats 😀 🤢
Google Gemini said:
Methylene blue is known to have a bitter or unpleasant taste that some describe as similar to dirt water. Here are a few things you could try mixing with it to potentially help improve the taste:
  • Sweeteners: Adding a small amount of a natural sweetener like honey or a sugar substitute such as stevia or erythritol might mask the bitterness.

  • Juices: Mixing methylene blue with a small amount of a strongly flavored juice, such as cranberry or grape juice, could help to cover up the taste.

  • Flavored Liquids: Consider using a flavored electrolyte drink or a sugar-free flavored water to dilute the methylene blue.
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Take caution if combining the Methylene Blue with Tesofensine or other SSRIs-

Tesofensine is a triple monoamine reuptake inhibitor, meaning it affects dopamine, serotonin, and norepinephrine. It is being studied as a potential treatment for obesity and other conditions, and has shown some promising results in reducing weight. However, its use with MAOIs (monoamine oxidase inhibitors) is not well-studied, and there are potential risks involved.

Methylene blue is a monoamine oxidase inhibitor (and, if infused intravenously at doses exceeding 5 mg/kg, may result in serotonin syndrome if combined with any selective serotonin reuptake inhibitors (SSRIs) or other serotonergic drugs (e.g., duloxetine, sibutramine, venlafaxine, clomipramine, imipramine).
 
Skidude said:
Take caution if combining the Methylene Blue with Tesofensine or other SSRIs-

Tesofensine is a triple monoamine reuptake inhibitor, meaning it affects dopamine, serotonin, and norepinephrine. It is being studied as a potential treatment for obesity and other conditions, and has shown some promising results in reducing weight. However, its use with MAOIs (monoamine oxidase inhibitors) is not well-studied, and there are potential risks involved.

Methylene blue is a monoamine oxidase inhibitor (and, if infused intravenously at doses exceeding 5 mg/kg, may result in serotonin syndrome if combined with any selective serotonin reuptake inhibitors (SSRIs) or other serotonergic drugs (e.g., duloxetine, sibutramine, venlafaxine, clomipramine, imipramine).
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I read that, and it kept me from my dose of selank. I did just bang 700mg of Semax. Let's see how well they play together.
 
I have not read up too much on serotonin syndrome, but it sounds like no fun from what I have read.
 
Skidude said:
I have not read up too much on serotonin syndrome, but it sounds like no fun from what I have read.
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I feel like I had some of that when I over dosed myself with Selank (probably why I was gun shy with mixing it with blue). I felt uncomfortable and withdrawn. My head was in a strange place.

Do not pin more than 1mg if you are pep sensitive.
 
I was introduced to a great website about 10 years ago, I have been a fan ever since!
Think about the "For Dummies" books but covering a wide array of subjects and condensed into short, entertaining, videos.
I have since shared it with many of my friends and would like to share it here.
This is a great subject to introduce Kurzgesagt to you all on as this video covers a few things relatable and important to us.
I am also taking this opportunity to adjust, maybe temporarily, my ava.
 
Skidude said:
After looking at many different options my first cycle was 4mg 5days on 2 days off for 6 weeks.
I am now ready for my next and will be stacking with overlaps as well- SS-31, Mots-C, NAD+
This is my current SS-31 protocol- Going with Basic first. 5mg a day also taking CoQ10,TMG,Lipo-c w/b12

Basic SS-31 Cycle (General Health & Mitochondrial Support)
Dosage: 5-10 mg subcutaneous (SQ) daily
Duration: 6-8 weeks
Break Between Cycles: 6-8 weeks off
Considerations:
Take on an empty stomach for better mitochondrial uptake.
Pair with Lipo-C, B12, or CoQ10 for enhanced mitochondrial function.
Combine with low-impact exercise (walking, bodyweight training) for best results.
Advanced SS-31 Cycle (Athletic Recovery & Performance)
Dosage: 10-20 mg SQ daily
Duration: 8-12 weeks
Break Between Cycles: Equal to cycle length (8-12 weeks)
Additional Support:
Lipo-C/B12 injections for metabolism & energy.
Creatine, TMG, and CoQ10 for added mitochondrial support.
Cold therapy or sauna use to enhance mitochondrial function.
Optional: Microdosing Approach (for Longevity & Maintenance)
Dosage: 5 mg SQ 3-4x per week
Duration: Ongoing with periodic breaks
Breaks: 2-4 weeks off every 3 months
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More info regarding dosing (from Reddit):

https://www.reddit.com/r/Peptides/comments/ib5t2n/comment/g2ipeqf
 
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Peloma said:
I find that one hard to believe.
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Yes, but I have no choice but to believe something positive about micro-dosing (which is what 4 mg daily would be compared to 40 mg daily). I have only 100 mg total from SRY 🙂
 
Calm Logic said:
Yes, but I have no choice but to believe something positive about micro-dosing (which is what 4 mg daily would be compared to 40 mg daily). I have only 100 mg total from SRY 🙂
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Definitely not a knock against you, or the benefit of taking a 4mg dose vs 40mg. I just don't see how every source is quoting the same, flawed study and they're like, "we're good with this..."
 
By @GimmeABreak, an interesting experience with SS-31, with more energy than MOTS-c:

GimmeABreak said:
I didn't notice much additional weight loss with SS31 after pinning for 2-3 months. For the first two-months I had great energy/focus from it, but can't really say it helped with weight or body composition.

I did notice some fat loss (maybe not weight, but belly fat) with MOTs-C. I didn't notice any energy increase with it but my waist size went down. This could have been from the Tirz but I think the MOTs played a role in it.

After a couple of months SS31 stopped giving any feels, even pinning a full 34mg vial (in 2 doses) on the same day, so I am taking a break for a month or two. I can't wait to revisit it and hope I get the feelz back.
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GimmeABreak said:
Hard to say, I don't get a lot of "feelz" from most of the peps I mentioned. NAD+ (not a pep) maybe a little bit of energy but no rush like others report. SS31 was great at first, I guess I am optimized now so I really don't get much from it or MOTs-C.
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GimmeABreak said:
Might want to consider adding a TMG supplement 30-60 minutes prior to NAD+ pin. It makes sure you have enough methyl donors to supply the NAD+. I take 1000mg 2x a day when taking NAD+, SS31 or MOTs-C.
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The International Peptide Society is recommending 200 mg per day???

They certainly seem to be:

peptidesociety.org

SS-31 - The International Peptide Society

SS-31 Szeto-Schiller-31 Elamipretide MTP-131 Bendavia SBT-272 Mitochondrial Antioxidant Support Contents Sequence: D-Arg-Dmt-Lys-Phe-NH2 Molar Weight: 639.8 g/mol Molecular Formula: C32H49N9O5 Most Frequent Uses: Mitochondrial support Neuroinflammation Memory/cognitive support Mitochondrial...
peptidesociety.org peptidesociety.org
  • SubQ dosage:
    • Supplied 100mg/ml
    • 2ml SubQ daily x 4 weeks
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Skidude said:
ss-31 energy is anecdotal..
However, the "feeling" is real.
But only you get it.
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And MOTS-c is banned by the World Anti-Doping Agency (WADA), unlike SS-31. So I assume that is more evidence that MOTS-c would potentially provide more of a boost than SS-31.
 
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Calm Logic said:
The International Peptide Society is recommending 200 mg per day???

They certainly seem to be:

peptidesociety.org

SS-31 - The International Peptide Society

SS-31 Szeto-Schiller-31 Elamipretide MTP-131 Bendavia SBT-272 Mitochondrial Antioxidant Support Contents Sequence: D-Arg-Dmt-Lys-Phe-NH2 Molar Weight: 639.8 g/mol Molecular Formula: C32H49N9O5 Most Frequent Uses: Mitochondrial support Neuroinflammation Memory/cognitive support Mitochondrial...
peptidesociety.org peptidesociety.org
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That would get expensive real fast. The most i took in this last cycle was 10mg. I didn't feel any increased benefit, but that's how these things work. Most of the benefit is in the background.
 
I tried to contact them (The International Peptide Society), but their online form isn't working. But I will try to contact them somehow when I get a chance to see if it is a typo.
 
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