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

#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.

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