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

#309

When talking about degradation, we are mostly talking after reconstitution. Like how long does reconstituted tirzepatide stay potent without significant degradation. Or how much potency loss does retatrutide suffer after freezing the reconstituted solution and thawing it back.

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#310

Some useful information for veterans and neophytes.

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#311

This is mostly fine, except I would not recommend khole for newbies. Khole has successfully been used by scammers to take people’s money (via her vendor “interviews” ).

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#312

Thanks for posting this in response to the article I posted. I thought this was something that required a prescription.
Has your father tried it?

#313

It’s available via grey market sources. The prescription version is extremely expensive. I have not yet obtained the peptide yet. It’s on my to do list.

#314

Degradation testing for reconstituted thymosine alpha 1 is finally underway for up to a 30 days. Should find out soon how stable that peptide is.

I’m not sure what that will imply for Zadaxin. Probably nothing, since they are probably using another formulation (could different buffering agent, solution, temp stability, etc) for it. Similar to tesamorelin and Egrifta.

#315

@John_Hemming You’re all about the mitochondria but I’ve not seen you speak much about SS-31/ Elamipretide.

Have you got any thoughts on it? Have you tried it or are you thinking of trying it?

#316

What does it do?

My view on short proteins is that if I need them my protocol in the round should provide them. My priority if anything is selective mitophagy.

#317

SS-31 aka Elamipretide

“Mitochondria are cellular hubs integral for metabolism, signaling, and survival. Mitochondrial dysfunction is centrally involved in the aging process and an expansive array of disease states. Elamipretide is a novel mitochondria-targeting peptide that is under investigation for treating several disorders related to mitochondrial dysfunction. This review summarizes recent data that expand our understanding of the mechanism of action (MOA) of elamipretide. Elamipretide is a potential first-in-class therapeutic that targets the inner mitochondrial membrane. Despite initial descriptions of elamipretide’s MOA involving reactive oxygen species scavenging, the last ten years have provided a significant expansion of how this peptide influences mitochondrial bioenergetics. The cardiolipin binding properties of elamipretide have been corroborated by different investigative teams with new findings about the consequences of elamipretide-cardiolipin interactions. In particular, new studies have shown elamipretide-mediated modulation of mitochondrial membrane electrostatic potentials and assembly of cardiolipin-dependent proteins that are centrally involved in mitochondrial physiology. These effects contribute to elamipretide’s ability to improve mitochondrial function, structure, and bioenergetics. In animal studies, elamipretide-mediated amelioration of organ dysfunction has been observed in models of cardiac and skeletal muscle myopathies as well as ocular pathologies. A number of clinical trials with elamipretide have been recently completed, and a summary of the results focusing on Barth syndrome, primary mitochondrial myopathy, and age-related macular degeneration, is also provided herein. Elamipretide continues to show promise as a potential therapy for mitochondrial disorders. New basic science advances have improved understanding of elamipretide’s MOA, enabling a better understanding of the molecular consequences of elamipretide-cardiolipin interactions.”

"By localizing to the IMM and associating with CL, elamipretide improves assembly of ETS complexes into respiratory supercomplexes and as a result, respiratory efficiency [55,56], thereby improving bioenergetics, reducing ROS production, and improving mitochondrial morphology in dysfunctional mitochondria.

Recent studies show that elamipretide interacts with proteins that are associated with the IMM, interact with CL, and are involved in oxidative phosphorylation. Elamipretide has also been recently shown to modulate mitochondrial membrane surface electrostatic properties, which may underpin its modulation of electron carrier properties and its ability to interact with ANT and ETS supercomplexes. These changes of membrane physical properties can themselves elicit improvements in overall mitochondrial function that are independent of alterations in constituent protein structure and function, and therefore reinforces elaimpretide’s ability to target mitochondrial health at multiple levels within the organelle itself.

Preclinical models of disease also show that elamipretide improves mitochondrial structure and function, enhances mitochondrial bioenergetics, and is associated with improvements in physiologic functions, such as cardiac and skeletal muscle performance, as well as improvements in age-related retinal dysfunction. Clinical trials also support elamipretide’s efficacy in mitochondrial-related diseases (eg, BTHS, mitochondrial myopathy, and AMD), although the results have been mixed, which may be due to a variety of factors including the difficulty in identifying appropriate endpoints, small patient populations, and inadequate treatment duration."

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#318

This is exactly how the gray market community does it for the GLP 1 peptides.

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#319

Playing around with the new Google Gemini video generator. How SS-31 works:

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#320

Is this free to use?

#321

“Mitochondrial dysfunction contributes to impaired myocardial energetics and performance in heart failure with preserved ejection fraction (HFpEF). Elamipretide (Ela) enhances mitochondrial bioenergetics in preclinical models, yet its relevance in HFpEF remains unclear. This study examined the effects of Ela on cardiac mitochondrial function, structure, and cardiovascular performance in a rodent HFpEF model…

…Ela modestly improved complex I and II respiration, whereas mitochondrial ultrastructure, cardiolipin composition, and tafazzin expression were unchanged. Diastolic dysfunction persisted, reflected by unchanged E/é, ventricular stiffness factor β, and titin phosphorylation. Compared to untreated HFpEF, systolic performance showed a mild decline, with small reductions in LV ejection fraction and end-systolic elastance. Accordingly, cardiac remodeling, including hypertrophy, fibrosis, and inflammatory activation, remained unaltered. Vascular stiffness slightly increased, while carotid reactivity and morphology were preserved. In conclusion, despite enhanced mitochondrial respiration following Ela treatment, no functional or structural benefits were observed in experimental HFpEF, suggesting limited therapeutic efficacy once HFpEF is established.”

Mitochondrial Targeting by Elamipretide Improves Myocardial Bioenergetics Without Translating into Functional Benefits in HFpEF Mitochondrial Targeting by Elamipretide Improves Myocardial Bioenergetics Without Translating into Functional Benefits in HFpEF - PMC

“SS-31 could effectively improve post-CA brain injury, in which the mechanism was potentially related to the inhibition of microglial ferroptosis and polarization through the regulation of Sesn2 signaling pathway.”

SS-31 improves post-cardiac arrest brain injury by inhibiting microglial ferroptosis and polarization SS-31 improves post-cardiac arrest brain injury by inhibiting microglial ferroptosis and polarization - PMC

“Excessive production of reactive oxygen species during in vitro embryo production can impair mitochondrial defense mechanisms, thereby reducing embryonic developmental competence. We investigated the effects of elamipretide, a mitochondrial-targeted antioxidant, on porcine oocyte maturation and subsequent embryo development in vitro. The results demonstrated that SS-31 enhanced the antioxidative capacity of oocytes by reducing intracellular reactive oxygen species levels, increasing glutathione content, improving mitochondrial membrane potential, and reducing DNA fragmentation, resulting in higher rates of oocyte maturation and blastocyst formation.”

Mitochondrial-Targeted Protective Potential of Elamipretide for the In Vitro Production of Porcine Embryos Mitochondrial-Targeted Protective Potential of Elamipretide for the In Vitro Production of Porcine Embryos - PMC

“This study found that PINK1/Parkin-mediated mitophagy was activated during tendon ossification, and the regulation of mitophagy could impact the osteogenesis of injured tendon-derived progenitor cells (inTPCs). Loss of Slc25a4 inhibited tendon ossification by downregulating the excessive mitophagy. Elamipretide, a targeted drug for ANT1, showed significant efficacy in treating Heterotopic ossification (HO).”

Targeting ANT1 to regulate PINK1/Parkin-mediated mitophagy is an effective treatment of trauma-induced tendon heterotopic ossification Targeting ANT1 to regulate PINK1/Parkin-mediated mitophagy is an effective treatment of trauma-induced tendon heterotopic ossification - PMC

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#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."

#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