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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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.
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?
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."
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
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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.
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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.
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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.
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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
- Open access paper: Elamipretide reverses female fertility decline during reproductive aging via regulating VEGF in oocytes
- Institution: College of Animal Science and Technology, Nanjing Agricultural University
- Country: China
- Journal Name: bioRxiv (Preprint Server)]
Study Design Specifications
Human Arm (In Vitro)
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Cohort: 14 patients undergoing intracytoplasmic sperm injection cycles.
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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.
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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.
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Intervention: Culture medium supplemented with 500 micromolar SS-31 peptide during in vitro maturation.
Mouse Arm (In Vivo & In Vitro)
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Species / Strain: Mouse; ICR strain.
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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.
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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.
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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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