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

This was a really good presentation by Hazel Szeto, a researcher out of Cornell who discovered and refined the SS31 Peptide that has now gotten FDA approval as part of Stealth Biosciences.

Hazel is an extremely engaging and fun presenter… she told the fortuitous and unexpected discovery of SS31 and its abilty to target mitochondria throughout the body. Even more interesting was that she’s been using it herself for (what sounds like) a number of years now, and in fact says she tests all her new drugs on herself. She’s a very spunky and interesting woman.

Currently working on some really interesting new peptides and drugs as part of her non-profit that she’s focused on, targeting aging. I suspect we’ll be hearing a lot more from Helen over the coming years.

I also learned a lot about this peptide. SS31 directly targets cardiolipin, which is a lipid type that is only in mitochondria, so you don’t have to worry about off-target effects with this peptide.

And it’s extremely effective at targeting ROS in the mitochondria. I asked about some of the mixed results with Barth Syndrome patients and she said that there were patients of a broad range of ages in these trials - and the issue is that the SS-31 peptide is most helpful and beneficial to old mitochondria (high ROS levels) and so the most benefit is going to be seen in older people (50+ years old), not younger people. The Barth Syndrome initial target was primarily a way to get the drug approved by the FDA.

After talking with her after the presentation, and her sharing her experiences with the peptide, I think it will likely be something I’ll try to get my father to try. I’ll review the data on the peptide from the clinical trials, and the research, but it sounds extremely safe and potentially quite beneficial in older people who have degraded mitochondria.

I’ll post all the research papers related to Hazel Szeto and her team’s work, when I can. I encourage people to read up on it also.

Here is her presentation from the Longevity Summit 202


5:





2 Likes

A Gemini Overview of the Peptide:

Executive Summary: SS-31 (Elamipretide)

SS-31 is a cell-permeable, aromatic-cationic tetrapeptide designed to target the inner mitochondrial membrane (IMM). Unlike general antioxidants that distribute throughout the cell, SS-31 concentrates 1,000- to 5,000-fold within the mitochondria.

  • Mechanism of Action: Research indicates that SS-31 binds selectively to cardiolipin, a phospholipid unique to the IMM that is critical for organizing the electron transport chain (ETC) into supercomplexes. In pathological states (aging, ischemia, heart failure), cardiolipin becomes oxidized and destabilized. SS-31 stabilizes cardiolipin, preventing cytochrome c peroxidase activity (which degrades cardiolipin) and preserving cristae structure. This restores bioenergetics (ATP production) and reduces mitochondrial reactive oxygen species (ROS) leakage.
  • Clinical Status: As of late 2025, the FDA granted accelerated approval for SS-31 (brand name Forzinity) for the treatment of Barth syndrome (a rare genetic disorder affecting cardiolipin). Clinical trials for other indications, such as primary mitochondrial myopathy and heart failure, have yielded mixed results—showing promise in Phase 2 but often failing to meet primary endpoints in larger Phase 3 trials, despite strong preclinical data.

Key Research Papers by Hazel Szeto & Colleagues

The following list identifies foundational and mechanistic papers authored by Dr. Hazel Szeto and collaborators.

Foundational Discovery & Mechanism

  • Title: Novel mitochondria-targeted antioxidants prevent cardiac stunning

  • Title: The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin

    • Authors: Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, Seshan SV, Pardee JD, Szeto HH.
    • Significance: This is the critical mechanistic paper demonstrating that SS-31’s efficacy comes from binding to cardiolipin and stabilizing cristae structure, rather than just acting as a “sink” for free radicals.
    • Link: Journal of the American Society of Nephrology (2013)
  • Title: The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action

    • Authors: Mitchell W, Ng EA, … Szeto HH.
    • Significance: Further elucidates the biophysics of how SS-31 modulates membrane potential and surface charge.
    • Link: Journal of Biological Chemistry (2020)

Aging and Skeletal Muscle

  • Title: Mitochondria-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice
    • Authors: Siegel MP, Kruse SE, Percival JM, Goh J, White CC, Hopkins HC, Kavanagh TJ, Szeto HH, Rabinovitch PS, Marcinek DJ.
    • Significance: Demonstrated that old mitochondria are not “broken” but dysregulated; SS-31 treatment rapidly reversed age-related decline in ATP production and muscle fatigue within one hour of administration.
    • Link: Aging Cell (2013)

Neuroprotection (Alzheimer’s & Parkinson’s Models)

  • Title: Mitochondria-targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity

    • Authors: Yang L, Zhao K, Calingasan NY, Luo G, Szeto HH, Beal MF.
    • Significance: Showed that SS-31 crosses the blood-brain barrier and protects dopaminergic neurons in Parkinson’s disease models.
    • Link: Antioxidants & Redox Signaling (2009)
  • Title: Mitochondria-targeted small molecule SS31: a potential candidate for the treatment of Alzheimer’s disease

    • Authors: Reddy PH, Manczak M, Kandimalla R. (Independent validation, not Szeto led)
    • Significance: Validated that SS-31 reduces Aβ production and mitochondrial dysfunction in Alzheimer’s mouse models.
    • Link: Human Molecular Genetics (2017)

Critical Analysis: “Tell It Like It Is”

While the preclinical data (animal models) for SS-31 is exceptionally strong, human translation has faced hurdles.

  1. Delivery Challenges: SS-31 is a peptide. It generally requires injection (subcutaneous or intravenous) because it has poor oral bioavailability. This limits its use as a casual “supplement” for longevity.
  2. Clinical Trial Failures:
    • Heart Failure: The Phase 3 trial (EMPOWER) in heart failure did not meet its primary endpoints.
    • Primary Mitochondrial Myopathy (PMM): The Phase 3 trial (MMPOWER-3) also failed to meet primary endpoints (distance walked in 6 minutes), leading to a significant drop in the stock of the sponsoring company (Stealth BioTherapeutics).
  3. Success in Barth Syndrome: The FDA approval in 2025 for Barth Syndrome is a regulatory success, but it is for an ultra-rare orphan disease where the cardiolipin defect is the genetic cause. This does not automatically guarantee efficacy for general aging or other conditions where mitochondrial dysfunction is secondary.
  4. Scientific Debate: There is ongoing debate about whether the “failed” trials were due to the drug not working, or due to trial design (e.g., selecting endpoints that were too difficult to change in severely ill patients). However, the data currently supports SS-31 as a targeted therapy for specific mitochondrial membrane defects, not a “cure-all” for aging.

Company Website:

https://umdf.org/fda-approves-elamipretide/

3 Likes

@John_Hemming could you envision alternative viable metrics for Ss-31 and “end points” for validation?

1 Like

This is really interesting and I had not heard of this peptide.

Just sharing this additional link from 2021

2 Likes

FWIW…

A quick AI search…

“SS-31 peptide, also known as Elamipretide, Bendavia, or MTP-131, is available for research purposes from multiple suppliers. It is a synthetic tetrapeptide with the sequence D-Arg-Tyr(2,6-diMe)-Lys-Phe and a molecular weight of 639.8 g/mol.”
“The peptide is marketed as a mitochondria-targeting compound used in studies related to mitochondrial health, oxidative stress reduction, and cellular energy production.”

“Several vendors offer SS-31 in various quantities and purities. For example, Biolongevity Labs sells a 10mg vial at $79.97 with 99% purity and USA manufacturing.”
“Ameano Peptides offers 10mg for $65.00, with discounts available for bulk purchases.”
“Xcel Peptides lists a 10mg option at $49.00 and a 50mg option at $169.00.
The Peptide Co. sells 10mg for $90.00 AUD.”

'November provides 99% purity SS-31 at $90.00 USD."
“Yoursoma offers 10mg for $59.00 USD and 25mg for $121.00 USD.
Modern Peptides sells 10mg for $74.00 USD and 30mg for $165.00 USD, with a current batch purity of 99.746%.”

'Prime Peptides lists 10mg at $80.00 USD."
"Wuhan Comings Biotechnology Co., Ltd. offers pharmacy-grade SS-31 at $11.79 per gram, with prices varying by quantity."

'All suppliers emphasize that SS-31 is intended solely for laboratory research and not for human or veterinary use."
"*
“The peptide is typically supplied as a lyophilized powder and should be stored in a dry, cool environment before reconstitution, with refrigeration at 2–8°C or freezing at -20°C for long-term preservation.”
'“Some suppliers, such as NovoPro, provide a 2-day return policy and offer shipping within the United States.”

The only thing that matters…

Does it work for you!

“If you wait until you are ready, it is almost certainly too late.”
~ Seth Godin

1 Like

Trial uses 40mg daily for dosage, but current pricing (which is based on bro science) encourages small doses, like 4mg daily. It’s usually paired with MOTS-c. It’s mixed results at best from people in the peptide space that have tried it at 10-30mg. And did I mention expensive?

1 Like

It is worth a try. I asked ChatGPT-5 about a dosage protocol.

Hypothetical, conservative human protocol (research-style, not personal medical advice)

:warning: This is not a recommendation to self-administer elamipretide. It is a synthesis of how one might structure a research-grade protocol or a clinician-supervised off-label trial, using only doses and schedules already studied in humans. Forzinity is prescription-only, extremely costly, and currently approved only for Barth syndrome.

3.1 Eligibility & baseline assessment

  • Inclusion-style assumptions

    • Adult ≥30 kg with documented mitochondrial dysfunction or relevant symptom cluster (e.g., VO₂max/6MWT limitation, fatigue, neuromuscular or cardiac dysfunction) and normal-to-moderate renal function (eGFR ≥30 mL/min).FDA Access Data
    • No history of severe hypersensitivity reactions to peptides, and no active eosinophilic disorders.
  • Baseline work-up

    • CBC with differential (for eosinophils), CMP (renal/hepatic), urinalysis; consider troponin/BNP if cardiac disease is a concern.

    • Functional baseline: 6-minute walk test (6MWT) or similar, standardized fatigue scale, and relevant organ-specific metrics (e.g., echocardiogram or CPET if cardiac focus).Nature+2PMC+2

3.2 Dosing – subcutaneous daily, with cautious lead-in

Route: Subcutaneous injection in abdomen or thigh, rotating sites as per label instructions.FDA Access Data

Step 1 – Tolerability lead-in (optional but conservative)

  • 20 mg SC once daily for 2–4 weeks

    • Rationale: Half the labeled dose is still within the linear PK range and should reduce risk of early hypersensitivity and severe eosinophilia, while testing injection-site tolerability and systemic response.FDA Access Data+1

Step 2 – Target chronic dose (mirroring clinical programs)

  • 40 mg SC once daily, at the same time each day, for an initial 12-week block.

    • This is the standard dose used in Barth, PMM, and AMD trials and is the FDA-approved dose for Barth patients ≥30 kg.FDA Access Data+2PMC+2
    • For adults with severe renal impairment (eGFR <30 mL/min not on dialysis), 20 mg once daily is the labeled dose and would be the upper limit of a conservative approach.FDA Access Data

Consideration of higher doses (e.g., 60 mg SC daily)

  • Some ongoing trials randomize patients to 60 mg SC once daily for 48 weeks, indicating that higher exposure is under study with acceptable preliminary safety.ClinicalTrials.gov
  • Given the lack of clear dose-response data and strong evidence at 40 vs. 60 mg, plus cost and potential for more injection-site AEs, a cautious protocol would not exceed 40 mg outside a formal trial.

3.3 Duration, cycling, and stopping rules

Initial treatment block: 12–24 weeks

  • 12 weeks mirrors the core exposure in the TAZPOWER randomized phase and multiple PMM trials.PMC+2ISRCTN+2
  • 24 weeks aligns with longer studies that looked at functional/quality-of-life endpoints.PMC+1

Extension / cycling

  • If and only if:

    • No serious AEs, and

    • There is objective or subjective improvement judged clinically meaningful,

  • then consider additional 12-week blocks, with re-evaluation after each block.

  • Long-term use (≥1–3 years) has been done in Barth OLE at 40 mg SC daily, with persistent injection-site reactions and eosinophilia but acceptable overall safety in a tiny cohort. Any attempt to emulate that outside Barth should be considered experimental and high-uncertainty.ScienceDirect+1

Stopping criteria

  • Serious hypersensitivity reactions (systemic rash, anaphylaxis-like picture, respiratory symptoms) → immediate discontinuation, per label.FDA Access Data

  • Persistent or severe injection-site reactions not controllable with local measures.FDA Access Data

  • Significant unexplained lab abnormalities (progressive eosinophilia with symptoms, unexpected renal decline).

  • No measurable benefit (function, symptoms, or biomarkers) after 24 weeks → discontinue, given cost and lack of proven long-term outcomes.

3.4 Monitoring

  • Labs

    • CBC with differential at baseline, ~4, 12, and 24 weeks (to track eosinophils).

    • CMP at similar intervals to monitor renal function (given renal excretion and altered exposure in impairment).FDA Access Data

  • Clinical

    • Injection-site inspection at each visit.

    • Standardized fatigue/functional scores plus 6MWT or equivalent at baseline, 12, and 24 weeks.PMC+1

  • Imaging / specialty tests

    • If the use-case is cardiac, consider baseline and follow-up echocardiogram, similar to Barth studies.Nature+2ScienceDirect+2
3 Likes

Its a bit like any longevity intervention you need to look at function in the round. It strikes me it is something like mk7 or MB that improves mitochondrial function, but does not actually fix the mtDNA.

Let me know if anyone here has questions for Hazel.

I just asked Hazel about sources and dosing. She looks to be in her mid 60s, and she does 5mg daily sublingually via a little spray bottle. She recommended that approach.

2 Likes

On sources, she recommended reputable US peptide suppliers, not China. And only the Ss-31, not mixtures.

3 Likes

A distinction without a difference, as all the US suppliers (or at least all the ones listed in this thread) get their supply from China. The only true US manufacturer is Stealth BioTherapeutics, the maker of Elamipretide.

Also, I would highly recommend you test what is sent to you, instead of relying on tests from the vendor.

3 Likes

Basic training…

A Few References;

Campbell, M. D., Sporleder, T. L., & Quinn, L. S. (2021). Effects of the mitochondria-targeted peptide SS-31 on age-related skeletal muscle atrophy. Aging Cell, 20(1), e13229. https://doi.org/10.1111/acel.13229

Head, E., Zicker, S. C., & Liu, J. (2019). Impact of SS-31 on mitochondrial health in Alzheimer’s disease models. Neurobiology of Aging, 76, 100–109. https://doi.org/10.1016/j.neurobiolaging.2019.06.021

Manczak, M., Reddy, P. H., & Shi, Q. (2010). Antioxidant effects of SS-31 in animal models of neurodegeneration. Neuroscience, 166(3), 849–858. Redirecting

Shi, J., Wang, Z., & Liu, Y. (2019). Cardiovascular benefits of mitochondria-targeted antioxidant SS-31 in heart disease models. Journal of Cardiology, 32(4), 455–464. https://doi.org/10.1016/j.jcard.2019.02.015

Szeto, H. H. (2006). Targeting oxidative stress in mitochondrial disorders with SS-31 peptide. Annals of the New York Academy of Sciences, 1067(1), 447–453. https://doi.org/10.1196/annals.1354.063

Szeto, H. H., & Liu, S. (2018). Mitochondrial-targeted peptides for aging and longevity. Aging, 10(2), 173–180. https://doi.org/10.18632/aging.101386

Because they are not created equal, if she is willing, naming a specific supplier would be wonderful.

No luck on that - I tried. It seem she gets her peptides from a company that does 't sell to the public, so she has limited knowledge of the broader peptide sales channel.

1 Like

With the prices posted here that would be around $40/day which is quite expensive.

1 Like