Hazel Szeto, SS-31 peptide, the World's First FDA-Approved Mitochondria-targeted Drug (Longevity Summit, 2025)

#322

If anybody knows a legit source for 100mg/vial × 10 vials for max 180 USD, please let me know.

#323

Not a chance. Cheapest I’ve seen is 50-mg vials x 10 for $320 plus shipping. Many online sources.

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#324

I saw 50mg kit for 225, which looked pretty good from what I was told. Out of stock now, unfortunately.

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#325

Thanks guys, keem em coming.

Going to ask Jennyschem if they can produce for relatively cheap. Will keep you guys updated.

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#326

Any EU people here with experience? I’d like to test it, but I don’t really want to order a full batch for 400 € just to find out if it does anything for me. Would be interested if anyone has ordered larger amounts, has tested vials, or knows a practical way to try a small amount first.

@Beth

Interesting. Are you still taking 4 mg/day?

Have you considered doing a small blinded self-experiment? For example, prepare active vs. empty/placebo injections, have someone else randomize/mix them, so you don’t know which period is which. Maybe even two blocks: one on, one off. Would be interesting to see if the effect holds up without expectancy bias.

Also, what else helped you with ADHD besides this?

#327

Maybe this is what they mean by ‘never meet your heroes.’ I’m really curious why she’s avoiding injections, which are way more effective. Sublingual bioavailability can’t hold a candle to injections. I think the reason is pretty simple: injections are a hassle, and sublingual still gives you some absorption, even if it falls way short. I mean, why did pharma companies even develop oral Semaglutide in the first place? Exactly because injections are such a pain."

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#328

Ovarian Rejuvenation: SS-31 Peptide Therapy Restores Oocyte Quality

Reproductive aging is a primary driver of female infertility, characterized by a steep decline in oocyte quality that complicates both natural conception and assisted reproductive technologies. While various natural compounds have been explored to combat this decline, highly efficient therapeutic strategies have remained elusive. A new study demonstrates that elamipretide (also known as SS-31 or Bendavia), a cell-permeating tetrapeptide, successfully reverses age-related oocyte defects and preserves ovarian function across human, mouse, and porcine models.

The core breakthrough rests on elamipretide’s unique ability to accumulate within the inner mitochondrial membrane, where it binds with high affinity to the phospholipid cardiolipin. By stabilizing cardiolipin, the peptide prevents its oxidation, protects mitochondrial cristae, and optimizes the mitochondrial electron transport chain. In aging oocytes, this targeted mitochondrial protection triggers a systemic cellular correction.

The researchers discovered that elamipretide rejuvenates aging ovaries by synergistically activating a previously unrecognized pathway: the Vitamin B6-VEGF axis. This metabolic and transcriptional rewiring simultaneously coordinates nuclear and cytoplasmic maturation. At the structural level, elamipretide therapy restores meiotic spindle assembly and chromosome alignment by upregulating microtubule acetylation. Concurrently, it rehabilitates compromised cytoplasmic actin networks via the upregulation of the regulatory protein ROCK1.

Beyond structural dynamics, the treatment resynchronizes intracellular organelles. Elamipretide clears mitochondria-driven oxidative stress, returns misplaced mitochondria and endoplasmic reticulum to their proper spatial zones, reduces excessive endoplasmic reticulum stress, and reinstates suppressed autophagic flux.

Remarkably, these benefits translated directly to functional fertility outcomes. In older human oocytes cultured in vitro, elamipretide supplementation significantly enhanced maturation, fertilization, and embryonic cleavage rates during intracytoplasmic sperm injection cycles. In vivo administration in aged mice rejuvenated the follicle reserve, increased ovulation numbers, and rescued the early embryonic developmental blocks that typically stall aged zygotes. This cross-species conservation establishes elamipretide as a highly promising therapeutic candidate for targeting tissue-specific reproductive senescence.

Actionable Insights

  • Targeted Cardiolipin Protection: Longevity interventions must prioritize inner mitochondrial membrane integrity. Cardiolipin oxidation is an upstream driver of cellular decay; compounds that stabilize this lipid network can preserve organelle architecture during aging.

  • Vitamin B6 as a Reproductive Synergist: The study highlights Vitamin B6 metabolism as a critical metabolic hub for oocyte quality. Optimizing pyridoxal 5-phosphate levels may complement mitochondrial therapeutics to support cellular energy production and vascular endothelial growth factor homeostasis in aging tissues.

  • Transient Treatment Windows: In vivo mouse data revealed that the fertility benefits of elamipretide were strictly limited to a short-term window of one month post-treatment. For translational longevity protocols, mitochondrial peptides may require precise, cyclical scheduling rather than continuous administration to achieve optimal therapeutic efficacy.

  • In Vitro Optimization: For clinicians and individuals utilizing assisted reproductive technologies, the direct supplementation of 200 micromolar elamipretide to human or mammalian culture medium represents an actionable method to enhance maturation and blastocyst formation rates in advanced maternal age cohorts.

Context

Study Design Specifications

Human Arm (In Vitro)

  • Cohort: 14 patients undergoing intracytoplasmic sperm injection cycles.

  • Advanced-Age Group: 3 patients; mean age 36.33 years (+/- 0.58); contributed 27 germinal vesicle oocytes randomly allocated to experimental (n = 15) or control (n = 12) conditions.

  • Younger Group: 4 patients; mean age 29.50 years (+/- 2.38); contributed 60 germinal vesicle oocytes randomly allocated to experimental (n = 31) or control (n = 29) conditions.

  • Intervention: Culture medium supplemented with 500 micromolar SS-31 peptide during in vitro maturation.

Mouse Arm (In Vivo & In Vitro)

  • Species / Strain: Mouse; ICR strain.

  • Cohorts: Aged female mice (8, 10, and 12 months old) and young female controls (6 to 8 weeks old). Male ICR mice (9 to 10 weeks old) utilized for in vitro fertilization.

  • Sample Size / Pooling: Minimum of 3 biological replicates per experiment. Specific assays pooled 15 oocytes (transcriptomics), 30 oocytes (ATP/qPCR), or 50 oocytes (mtDNA/Western blot) per group to achieve adequate signal thresholds.

  • In Vivo Regimen: Intraperitoneal injections of elamipretide dissolved in normal saline. Dose-escalation tested 3, 5, and 10 mg/kg/day across durations of 3, 7, and 10 days. Optimal protocol determined as 5 mg/kg/day for 7 days. Control groups received equivalent volume vehicle saline injections.

Porcine Arm (In Vitro Validation)

  • Model: Prepubertal gilt oocytes subjected to hydrogen peroxide-induced oxidative stress to mimic accelerated aging phenotypes. Dose-response curve identified 1 millimolar elamipretide as optimal cross-species rescue concentration.

Novelty

This paper identifies a previously uncharacterized pathway for ovarian rejuvenation: elamipretide-driven activation of the Vitamin B6-VEGF axis to orchestrate both nuclear and cytoplasmic oocyte maturation.

While elamipretide’s cardiolipin-binding properties are well-documented in cardiac and renal ischemia models, this study proves its therapeutic capacity is conserved inside the mammalian germline across species, including human clinical specimens.

Limitations

  • Transient Efficacy Window: The physiological benefit in mice is short-lived, failing completely after one month post-injection. This demonstrates that elamipretide acts as a temporary metabolic stabilizer rather than a tool capable of permanently reprogramming the ovarian aging clock or replenishing depleted stem cell niches.
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Recharging the Biological Clock: Multimodal Strategies to Combat Ovarian Aging
#329

It looks like the next step is to refine and directly inject mitochondria, can’t wait!

#330

Lots of Mitrix / Tom Benson Coverage in these threads:

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#331

Thanks, I missed those in my search.

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#332

I was waiting for her to ask if she could use mitochondria from pigs but she never did. He made it sound like you do need to match somehow, but didn’t really have all the details which probably need to be studied carefully.

#333

Ok, after reading tons of articles about SS-31 the past couple of weeks, I am of the humble opinion that is a sufficient dosing regimen:

50 mgs/day, 3 days on, 4 days off and repeat for another week or another two weeks, MAX.

That’s it.

SS-31 has so much potential. I’m in awe.

For the first time in my life I can honestly say that this substance fairly resembles the fountain of youth.

BUT

Absolutely need to test for purity and validity.

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#334

What kinds of articles have you been reading? Published journal articles, or sensationalized articles created by people who are directly or indirectly selling it on the grey market?

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#335

@RapAdmin FWIW on other platforms, even telegram, also on skool, The powers that be are shutting down groups, deleting members for discussing purchasing grey peptides.

Sadly just mentioning the long reach of those who’s profit and reputation is at risk.

I think saying “Uther on telegram” is ok. But giving more details on actually executing purchases is into a risky area. Other groups are saying they should move such detailed discussions more to the site Signal… Even Telegram is not totally safe. Uther got de plateformed a few weeks ago and had to open Uther-2.0 on Telegram. One skool group owner told us that PM on skool discussions are being monitored.

This said; I’ll comment I’ve recently bought off Uther on Telegram and nexaph.com. I can offer simplier helps via email; csmith@javadepot.com . I can’t offer detailed crypto steps which often end up being unique to what works for the individual. I’ve moved to Kraken Pro from Exodus even though Exodus is difficult to use its MUCH easier to use then Kraken Pro. The #1 reason why I moved is that kracken pro will direct ACH from my bank account for almost zero cost. And conversion is cheaper. Otherwise I hate crypto and end to end transaction costs are insane. Can exceed 10% easily for all the costs at each step. But at 10x cheaper I guess one can toss the transaction costs with exodus et al.

Take care, all, curt

#336

Platform owners make the platform rules. This is normal and expected since these are platforms by companies with their own terms of services. If people want to talk about these things, they should move off those platforms and host their own.

1 Like
#337

AI summary of the abstracts of the very latest paywalled studies on SS-31/Elamipretide

Executive Summary

Elamipretide (SS-31) is a mitochondria‐targeted tetrapeptide that binds cardiolipin and mitochondrial proteins (notably the ANT/ATP synthasome) to improve mitochondrial energetics and reduce oxidative stress. Across 13 studies (rodent, large-animal, and human), elamipretide consistently improves mitochondrial function and physiological performance in aging or disease models by enhancing ADP transport, boosting ATP production, and lowering reactive oxygen species (ROS). For example, in aged mice it restores muscle and cardiac bioenergetics (↑ATPmax, ↑mitochondrial coupling) and reverses diastolic dysfunction. In diabetic and inflammatory disease models it prevents organ injury: in db/db mice it stopped progression of diabetic nephropathy (↓albuminuria, preserved mitochondrial superoxide levels), and in LPS-treated mice it fully reversed hippocampal mitochondrial dysfunction and cognitive deficits.

By contrast, clinical trials in humans have been mixed. In heart failure with reduced EF (PROGRESS-HF), elamipretide (4–40 mg/d for 28d) was well-tolerated but did not significantly improve left ventricular remodeling (LVESV unchanged vs placebo). Similarly, in the MMPOWER‐3 trial (N=218), 24-week treatment (40 mg/d SC) in primary mitochondrial myopathy patients failed to improve 6-minute walk distance or fatigue. However, post hoc analyses suggest benefits in specific genetic subgroups, especially CPEO and nDNA maintenance disorders.

Mechanistically, elamipretide improves mitochondrial ADP sensitivity via ANT interaction, reduces pathological protein S-glutathionylation, stabilizes cardiolipin and the ATP synthasome, and increases ATP production efficiency while reducing ROS. Across studies, it is consistently well tolerated with mostly mild injection-site reactions.

Key Insights (distinct findings)

  • ANT-dependent ADP transport restoration: SS-31 increases mitochondrial ADP uptake by improving ANT function and reducing S-glutathionylation, restoring energetic flux in aged tissue.

  • Increased ATP production efficiency: Restores ATPmax and coupling efficiency in aged skeletal muscle without increasing mitochondrial number, indicating functional rather than biogenic effects.

  • Reversal of age-related muscle decline: Improves endurance, muscle mass, and fatigue resistance in aged mice with significantly enhanced treadmill performance.

  • Reversal of cardiac aging phenotype: Normalizes diastolic function, reduces hypertrophy, and improves exercise capacity in aged hearts while reducing proton leak and ROS.

  • Neuroprotection under inflammatory stress: Prevents LPS-induced cognitive impairment via preservation of hippocampal mitochondrial function and synaptic integrity.

  • Diabetic nephropathy prevention: Blocks albuminuria progression and mitochondrial oxidative stress in db/db mice, preserving renal cardiolipin metabolism.

  • Hemorrhagic shock protection: Reduces kidney and cardiac injury markers and lowers inflammatory cytokines in large-animal trauma models.

  • Human HFrEF: no structural benefit: No improvement in LV remodeling or systolic function despite good tolerability.

  • Human PMM: no global functional benefit: No significant improvement in 6MWT or fatigue in heterogeneous mitochondrial disease population.

  • Genotype-specific response: Significant benefit in CPEO and mitochondrial DNA maintenance disorders, suggesting responder stratification is critical.

  • Barth syndrome: delayed benefit signal: No short-term effect, but open-label extension showed improvements in exercise and fatigue metrics.

  • Excellent safety profile: Across all studies, adverse effects remain mild and mostly injection-site related.

Table 1. Study designs and key results (with direct PubMed links)

PMID (Year) & Reference Model/Type N (per grp) Dose/Regimen Primary Endpoints / Outcomes Main Findings (elamipretide vs control) Limitations Direct Link
41335372 (2019) Mouse (LPS neuroinflammation) ~10/group 3 mg/kg/day i.p. Memory, hippocampal function Rescued cognitive deficits, restored synaptic proteins and mitochondrial function Acute inflammatory model https://pubmed.ncbi.nlm.nih.gov/41335372/
40816230 (2019) Mouse (aging muscle) 7–10/group 3 mg/kg/day i.p. ×8 wk ATPmax, P/O, endurance Restored mitochondrial energetics and exercise capacity in aged mice Female-only cohort https://pubmed.ncbi.nlm.nih.gov/40816230/
41206662 (2020) Mouse (cardiac aging) 8–10/group 3 mg/kg/day i.p. ×8 wk Diastolic function, MPI Reversed cardiac aging phenotype and improved exercise tolerance No systolic EF improvement https://pubmed.ncbi.nlm.nih.gov/41206662/
41966639 (2020) Human (HFrEF RCT) ~71 total 4 mg or 40 mg SC daily ×28d LVESV by MRI No improvement in LV remodeling or function Short duration trial https://pubmed.ncbi.nlm.nih.gov/41966639/
41801306 (2020) Mouse (db/db diabetic nephropathy) Not stated ~5 mg/kg/day i.p. Albuminuria, renal ROS Prevented nephropathy progression and oxidative damage Translation unknown https://pubmed.ncbi.nlm.nih.gov/41801306/
42082001 (2020) Human (Barth syndrome RCT + OLE) 12 40 mg/day SC ×12 wk + OLE 6MWT, fatigue No RCT effect; open-label showed functional improvement Very small N, open-label bias https://pubmed.ncbi.nlm.nih.gov/42082001/
42290373 (2023) Human (PMM RCT) 218 40 mg/day SC ×24 wk 6MWT, fatigue No improvement in primary outcomes Heterogeneous population https://pubmed.ncbi.nlm.nih.gov/42290373/
41027799 (2024) Human subgroup (MMPOWER-3 post hoc) Subgroups (~6–20) 40 mg/day SC ×24 wk Genotype-specific 6MWT Significant improvement in CPEO and nDNA maintenance disorders Post hoc exploratory https://pubmed.ncbi.nlm.nih.gov/41027799/
41233677 (2023) Mouse (mechanistic aging study) 8–10/group 3 mg/kg/day ×8 wk ANT function, ADP flux Increased ANT-mediated ADP uptake, reduced S-glutathionylation Translational uncertainty https://pubmed.ncbi.nlm.nih.gov/41233677/
40785393 (2023) Pig (hemorrhagic shock) ~9/group 0.25 mg/kg bolus + infusion Organ injury markers Reduced creatinine, troponin, inflammation Acute model only https://pubmed.ncbi.nlm.nih.gov/40785393/
39962181 (2019) Mouse (LPS inflammation) ~10/group 3 mg/kg/day i.p. Cognitive performance Reversed neuroinflammation-induced memory deficits Acute injury model https://pubmed.ncbi.nlm.nih.gov/39962181/
42229401 (2024) Human (dry AMD trial) Not reported SC daily Geographic atrophy No published efficacy results Likely incomplete/negative https://pubmed.ncbi.nlm.nih.gov/42229401/
42358073 (2024) Human (mitochondrial genetics) Subgroups (~12–20) 40 mg/day SC ×24 wk 6MWT by genotype Strong response in CPEO subgroup (+37 m) Post hoc analysis https://pubmed.ncbi.nlm.nih.gov/42358073/

Synthesis (high-level)

Across species, SS-31 shows a highly consistent pattern:

  • Strong mitochondrial bioenergetic rescue in preclinical models
  • Robust organ protection under stress conditions
  • Clear mechanistic validation (ANT, cardiolipin, ATP synthasome stabilization)
  • Weak but highly context-dependent clinical efficacy
  • Strong signal that patient selection is the key limiting factor
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#338

TL;DR

Case study data on 5 people using SS-31 (1-2mg over 60-70 days) shows improvements in mitochondrial efficiency markers (ATP5B) roughly double that seen with MOTS-c, though DRP1 fusion/fission balance improved less than with MOTS-c. Higher doses (2mg) outperformed 1mg. The creator’s own results were “lukewarm” but he attributes this to confounding factors, mainly a sustained calorie surplus, rather than the peptide itself, and is now moving to 2mg/75-day cycles going forward. Side effect profile for SS-31 appears very clean compared to MOTS-c (which shows more injection site reactions).

Actionable Insights

  • Dose matters more than duration here. The 2mg/day cohort showed bigger improvements across markers than the 1mg group. If budget allows, front-loading dose over stretching duration looks like the better lever, at least based on this small sample.
  • Diminishing returns above a certain dose. A podcast guest reportedly ran 10mg daily and reported little difference versus 2mg, suggesting there’s a ceiling where extra spend stops buying extra benefit.
  • Confounders will wreck your ability to read the data. The creator was simultaneously running SLU-PP-332, Human Growth Hormone-related compounds, and a metformin experiment during parts of his cycle, which he flags as making his own numbers hard to interpret. If you’re trying to isolate SS-31’s effect, running it in isolation (like the five case-study subjects did) will give you cleaner signal than stacking.
  • Watch calorie surplus as a background variable. The creator links his own weak mitochondrial marker response, and worsening heart rate variability and organ-age scores, to an unnoticed ~500 kcal/day surplus rather than to the peptide failing. This is a good example of why isolating a single intervention’s effect requires controlling diet and lifestyle noise, not just the compound itself.
  • Injection timing relative to meals may matter for acute glucose response, based on a small self-experiment (pre- vs post-breakfast dosing), though this is anecdotal n=1 territory and shouldn’t be over-indexed.

Key Points

Mitochondrial marker results (5-person case study, 1-2mg, 60-70 days):

  • ATP5B (mitochondrial synthase efficiency marker) improved by an average of 18.5 points, roughly double the ~9.5 point improvement seen with MOTS-c in a separate 4-person case study.
  • DRP1 (fusion/fission balance marker) improved by only 7 points with SS-31 versus ~13 points with MOTS-c, suggesting MOTS-c may have an edge on this particular marker.
  • Glucose response (epigenetic marker) improved by 8 points on average; HbA1c-equivalent epigenetic marker improved by 6 points, though individual variation was large (one subject improved 38 points on glucose, another saw no meaningful change).
  • Response magnitude tracked with dose: the 2mg subjects had bigger improvements than the 1mg subjects.

Creator’s personal results and caveats:

  • His own DRP1 improved by only 3 points and ATP5B by just 1 point, a weak response he attributes to running a 1mg dose (lowest effective dose, chosen to manage cost) and to a prolonged calorie surplus rather than genuine treatment failure.
  • Organ-age markers moved unfavorably during this period (kidney age +1.5 years, heart age +2.2 years), and heart rate variability declined, all changes he attributes primarily to caloric excess, late eating windows, and larger dinners rather than to SS-31 itself.
  • Gut and protein-metabolism markers (fecal calprotectin-type markers, nitrogen breakdown byproducts) also pointed toward general overconsumption, particularly excess protein intake above roughly 1g/lb bodyweight.
  • He was simultaneously running SLU-PP-332 (a mitochondrial biogenesis/exercise-mimetic compound) with a 10-day overlap, and briefly trialled Saturday-only metformin (850mg) as an mTOR inhibitor, both of which he flags as confounds muddying his own data.

Practical protocol notes:

  • Going forward, the plan is 2mg/day for 75 days every six months, up from the previous 1mg/70-day cycle, using 50mg vials from Elovian Labs, which the creator notes are purity- and sterility-tested (a distinction he says many peptide suppliers skip). This puts an extended cycle at roughly £390 despite more than doubling total peptide use, since larger vials reduce shipping vial waste and per-mg cost.
  • Sequencing logic for SS-31 vs. MOTS-c: the “hardware first” heuristic (SS-31 repairing the inner mitochondrial membrane/cardiolipin before layering on MOTS-c) is a reasonable starting strategy, though the creator notes people who are more metabolically unhealthy tend to respond particularly well to MOTS-c specifically, so the ideal starting point may end up being individualized once better diagnostics exist.
  • Side effects: SS-31 was reported as very well tolerated, with only one anecdotal report of mild stimulation in someone unusually sensitive to dopaminergic compounds. MOTS-c showed more injection-site redness by comparison.
#339

Sounds like the calorie suplus might have been the least of his worries in terms of confounders.

Link to study?

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#340

He does run the website. Not a rigorous study like we’re used to it seems but he is pretty intensive with gathering biomarker data. Probably from some of his clients, so he’d likely know what they are taking overall.

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#341

Thanks for linking to it. Very cool report if the TrueHealth epigenetic reports are to be trusted.