TL;DR: SS-31 (elamipretide) is a synthetic mitochondria-targeting tetrapeptide that binds cardiolipin in the inner mitochondrial membrane, stabilising cristae and supporting ATP production. It is the most clinically advanced mitochondrial peptide, with human trials in mitochondrial disease and heart failure and a 2025 FDA approval for Barth syndrome. Most broader longevity claims remain preclinical.
What SS-31 actually is
SS-31 is a synthetic, cell-permeable tetrapeptide with the sequence D-Arg-2’,6’-dimethyltyrosine-Lys-Phe-NH2. The “SS” refers to Szeto-Schiller, the two researchers who first described this family of aromatic-cationic peptides. In its clinical development programme the same molecule is called elamipretide (and, more recently, the brand name Forzinity).
What makes SS-31 unusual is its targeting. Despite carrying a net positive charge, it crosses the plasma membrane without needing a transporter and concentrates heavily at the inner mitochondrial membrane, where it accumulates far above its extracellular concentration. Once there, its defining action is binding to cardiolipin, a distinctive phospholipid found almost exclusively in that membrane.
Cardiolipin is the structural scaffold that holds the respiratory chain together and shapes the folded cristae where ATP is generated. When cardiolipin is damaged by oxidative stress or genetically abnormal, the cristae destabilise, electron transport becomes leaky, and cells produce less energy while generating more reactive oxygen species. By associating with cardiolipin, SS-31 is thought to help preserve cristae architecture, keep respiratory supercomplexes organised, and reduce that oxidative leak. A detailed 2020 biophysical study reframed part of this mechanism as electrostatic: SS-31 partitions into the membrane interface and modulates its surface charge, which in turn affects how ions and proteins distribute at the membrane.
What the research shows
SS-31 is, by a wide margin, the most clinically developed mitochondrial peptide, so the evidence here is stronger and more honest to report than for most research peptides. It still comes with important caveats.
- 1
MMPOWER-2
Crossover trial hinted at a dose-related six-minute-walk improvement.
- 2
MMPOWER-3
Pivotal phase 3 (218 patients) missed its primary endpoints.
- 3
PROGRESS-HF
Phase 2 heart-failure trial: well tolerated, no LV-volume benefit.
- 4
TAZPOWER + extension
Barth syndrome trial showed muscle-strength gains over time.
- 5
Sept 2025
FDA accelerated approval for Barth syndrome — a first for the class.
Primary mitochondrial myopathy
Two randomised trials tested elamipretide in adults with genetically confirmed primary mitochondrial myopathy. An earlier crossover study (MMPOWER-2) suggested a dose-related improvement in six-minute walk distance. The larger, pivotal phase 3 trial (MMPOWER-3), which randomised 218 participants, did not meet its primary endpoints for the six-minute walk test or a fatigue score. A later post-hoc analysis found a possible benefit in a genetic subgroup with nuclear DNA maintenance defects, which is now being tested prospectively rather than treated as settled.
Barth syndrome
The most decisive human data come from Barth syndrome, a rare X-linked disorder in which cardiolipin metabolism is directly disrupted, making it a mechanistically ideal target. The TAZPOWER trial and its long-term open-label extension reported improvements in skeletal muscle strength and functional measures over time. On the strength of that data, elamipretide received FDA accelerated approval in September 2025, the first approval ever for a mitochondria-targeted peptide.
Heart failure
Cardiac muscle is energy-hungry and cardiolipin-rich, so heart failure has long been a target. The phase 2 PROGRESS-HF trial in patients with reduced ejection fraction found that a single 4-week course of elamipretide did not significantly change left-ventricular volumes versus placebo, though it was well tolerated. Cardiac research continues, but this is a clear example of a plausible mechanism not translating into a short-term clinical win.
The honest summary: SS-31 has genuine, high-quality human data, but that data is a mix of positive, negative, and subgroup-only results. Approval is limited to one rare genetic disease. The broad “mitochondrial rejuvenation” and anti-aging claims found on supplement pages rest largely on animal and cell studies, not confirmed human outcomes.
How SS-31 relates to MOTS-c and NAD+
SS-31 is often stacked conceptually with MOTS-c and NAD+ under the “mitochondrial support” umbrella, but the three act through genuinely different mechanisms. Understanding the contrast matters more than the marketing category.
| Feature | SS-31 (elamipretide) | MOTS-c | NAD+ (and precursors) |
|---|---|---|---|
| Class | Synthetic mitochondria-targeting tetrapeptide (4 aa) | Mitochondrial-derived signalling peptide (16 aa) | Coenzyme / redox cofactor |
| Primary mechanism | Binds cardiolipin, stabilising inner-membrane cristae | Activates AMPK via the AICAR pathway; nuclear signalling | Fuels sirtuins and redox reactions central to energy metabolism |
| Where it acts | Inner mitochondrial membrane (structural) | Nucleus and cytoplasm (signalling) | Whole-cell redox and enzymatic reactions |
| Main research focus | Cristae integrity, bioenergetics, cardiac and muscle disease | Insulin sensitivity, exercise, metabolism | Cellular energy, DNA-repair signalling, aging |
| Human evidence | Multiple trials; one FDA approval (Barth syndrome) | Early; mostly animal, small human exercise arm | Precursor trials ongoing; results mixed |
The simplest way to frame it: SS-31 is a structural repair concept (protect the membrane machinery), MOTS-c is a signalling concept (tell the cell to adapt like it does to exercise), and NAD+ is a fuel-and-cofactor concept (supply the currency those reactions run on). They target different layers of the same system, which is why researchers study them separately rather than assuming they are interchangeable.
Practical and regulatory context
For anyone comparing the research landscape, a few points are worth keeping straight. SS-31 is administered by injection in clinical studies; oral bioavailability is poor for a charged peptide of this type. It is generally reported as well tolerated in trials, with injection-site reactions being the most common finding, but tolerability in a monitored trial is not the same as an established safety profile for unsupervised use.
Regulatory status also differs sharply from most peptides discussed online. Elamipretide is now an approved medicine in the United States for one specific rare disease. That approval does not make research-grade SS-31 reference material a licensed product in the EU, nor does it validate the anti-aging positioning it is often marketed with. Material sold for laboratory use is exactly that, and in the EU it is not authorised for human administration.
If you are documenting reconstitution volumes or comparing concentrations across studies for reference purposes, our research calculator can help keep those figures organised. None of this constitutes dosing guidance.
Frequently Asked Questions
Is SS-31 the same as elamipretide?
Yes. SS-31 is the original laboratory designation from the Szeto-Schiller peptide series, and elamipretide is the international nonproprietary name used in clinical development. Forzinity is the approved brand name. All three refer to the same tetrapeptide molecule that binds cardiolipin in the inner mitochondrial membrane.
What does SS-31 do to mitochondria?
In research models, SS-31 concentrates at the inner mitochondrial membrane and binds cardiolipin, the phospholipid that scaffolds the respiratory chain. This is reported to stabilise cristae structure, help keep respiratory complexes organised, support ATP output, and reduce oxidative byproducts. These are mechanistic findings, not confirmed clinical outcomes for general use.
Is SS-31 FDA approved?
Elamipretide received FDA accelerated approval in September 2025 for Barth syndrome, a rare genetic mitochondrial disorder. This was the first approval of any mitochondria-targeted peptide. It is not approved for aging, general fatigue, heart failure, or performance, and research-grade SS-31 is not an authorised medicine in the EU.
Did SS-31 work in heart failure trials?
The phase 2 PROGRESS-HF trial tested elamipretide in patients with reduced-ejection-fraction heart failure over four weeks. It was well tolerated but did not significantly improve left-ventricular volumes versus placebo. Cardiac research continues, but short-term clinical benefit in heart failure has not been demonstrated in that study.
How is SS-31 different from MOTS-c?
They act on different layers of mitochondrial biology. SS-31 is a structural, membrane-targeting peptide that binds cardiolipin. MOTS-c is a signalling peptide that activates the AMPK metabolic-sensor pathway, mimicking some effects of exercise. SS-31 has far more advanced human clinical data, including an approved indication.
Can you take SS-31 for anti-aging?
No credible human trial supports SS-31 for general anti-aging or longevity. The anti-aging framing comes largely from animal and cell studies. Its only approved human use is a single rare disease. Research material is sold for laboratory use only and is not authorised for human administration in the EU.
References
- Mitchell W, Ng EA, Tamucci JD, et al. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. Journal of Biological Chemistry. 2020;295(21):7452-7469.
- Tung BC, Varzideh F, Farroni E, Mone P, Kansakar U, Jankauskas SS, Santulli G. Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential. International Journal of Molecular Sciences. 2025;26(3):944.
- Karaa A, Bertini E, Carelli V, et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023;101(3):e238-e252.
- Karaa A, Haas R, Goldstein A, et al. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. Journal of Cachexia, Sarcopenia and Muscle. 2020;11(4):909-918.
- Reid Thompson W, Hornby B, Manuel R, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genetics in Medicine. 2021;23(3):471-478.
- Hornby B, Reid Thompson W, Almuqbil M, et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genetics in Medicine. 2024;26(6):101138.
- Daubert MA, Yow E, Dunn G, et al. Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. Journal of Cardiac Failure. 2020;26(5):429-437.
- Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021;12(1):470.
Research-use-only disclaimer: This article is an educational reference for laboratory and scientific interest only. It is not medical advice and does not describe or recommend human dosing. SS-31 (elamipretide) as a research material is not authorised for human consumption in the EU. Approved medical use is limited to specific licensed indications under medical supervision. Always consult qualified professionals and follow applicable laws.