Mitochondrial peptides have one real success so far: SS-31 (elamipretide) won FDA accelerated approval on September 19, 2025 as Forzinity, the first treatment for Barth syndrome, a rare genetic disease.[8] The two best-known peptides encoded by mitochondrial DNA, humanin and MOTS-c, have never been tested as treatments in a published human trial; their benefits come from cells, worms and mice.[5][3]
This page covers the key studies behind each, what’s established and what isn’t. For background on aging-focused compounds, see our longevity peptides hub.
Bottom line
| Peptide | What it is | Best human evidence | Status (Oct 2026) |
|---|---|---|---|
| SS-31 / elamipretide | Lab-designed 4-amino-acid peptide that targets mitochondria | Small Barth syndrome trial plus extension; larger trials missed goals[10][11] | FDA-approved for Barth syndrome only[9] |
| MOTS-c | 16-amino-acid peptide encoded in mitochondrial DNA (2015) | None for MOTS-c; one small trial of an analog[6] | Not approved[5] |
| Humanin | 24-amino-acid peptide encoded in mitochondrial DNA (2001) | Only studies measuring natural levels[3] | Not approved |
Two kinds of “mitochondrial peptide”
The phrase gets used for two different things:
- Mitochondrial-derived peptides are made from short stretches of the mitochondria’s own DNA. Humanin was found in 2001 while screening for genes that protected nerve cells from Alzheimer’s-related damage.[1] MOTS-c was identified at the University of Southern California in 2015.[2] They seem to act as signals between mitochondria and the rest of the body.
- Mitochondria-targeted peptides are designed in the lab to enter cells and concentrate in mitochondria. SS-31 binds cardiolipin, a fat in the inner mitochondrial membrane that holds the energy-producing machinery together.[9]
Key studies: SS-31 (elamipretide)
TAZPOWER, Barth syndrome (2021). In this 12-patient trial, the randomized, placebo-controlled crossover phase missed its primary goals. In the open-label extension that followed, 6-minute walk distance improved by about 96 meters at week 36.[10]
FDA approval (2025). FDA based its accelerated approval on improved strength of the knee-straightening muscle, which it considers reasonably likely to predict real benefits such as walking farther. The company must run a confirmatory randomized trial.[8] The label limits use to Barth syndrome patients weighing at least 30 kg; injection-site reactions were the most common side effect.[9]
MMPOWER-3, mitochondrial myopathy (2023). In 218 adults with primary mitochondrial myopathy, 24 weeks of elamipretide did not beat placebo on walking distance or fatigue.[11]
Older adults (2021). A single infusion in 39 adults aged 60 to 85 produced only a borderline change in muscle energy production and no change in fatigue.[12]
Key studies: MOTS-c
Discovery in mice (2015). Mice on a high-fat diet given MOTS-c were protected from weight gain and insulin resistance. The peptide acted largely on muscle, through the energy sensor AMPK.[2]
Exercise and aging (2021). MOTS-c improved running capacity in young, middle-aged and old mice. In 10 young men, a cycling session raised natural MOTS-c about 12-fold in muscle.[4]
CB4211 analog (2021). In a phase 1b trial in 20 adults with obesity and fatty liver, 25 mg daily for 4 weeks lowered the liver enzyme ALT and modestly lowered blood sugar, but liver fat fell similarly with placebo.[6] In 2023 the developer said the formulation was not suitable for further development.[7]
FDA’s 2026 review found no clinical studies or human exposure data for MOTS-c itself by any route.[5]
Key studies: humanin
Discovery (2001). Humanin blocked nerve-cell death caused by several familial Alzheimer’s genes and by amyloid-beta in lab dishes.[1]
Lifespan and healthspan (2020). Extra humanin lengthened lifespan in worms, and twice-weekly injections of the analog HNG in middle-aged mice improved metabolic markers and lowered inflammation markers. In people, children of centenarians had much higher blood humanin than age-matched controls, an association rather than proof of cause.[3]
Established vs preliminary
Established:
- Elamipretide improves knee muscle strength in Barth syndrome enough for accelerated approval.[8]
- Humanin and MOTS-c are natural peptides that circulate in human blood and respond to exercise and age.[3][4]
Preliminary:
- Any benefit of these peptides for healthy aging, energy or weight loss in people.
- Whether injected MOTS-c or humanin reaches useful levels or is safe long term.
- Whether elamipretide’s strength gains translate into real-world function, which the confirmatory trial must show.
Safety: what’s known
Only elamipretide has a real human safety record. In trials, the most common side effects were mild to moderate injection-site reactions, and the label also warns about serious allergic and skin reactions.[8][9]
For MOTS-c, FDA found no animal toxicity studies and no human exposure data, and raised concerns about immune reactions to impurities or clumped peptide in products sold online.[5] In the CB4211 analog trial, injection-site reactions were the main side effect.[6] For humanin, there is no human safety data because it has never been given to people in a published study.
Limitations
- Small trials. The pivotal Barth syndrome trial had 12 patients.[10]
- Mouse-to-human gap. Most of the excitement about MOTS-c and humanin comes from rodent and worm studies, which often fail to translate.
- Industry ties. Several key humanin and MOTS-c papers come from researchers linked to CohBar, the company that developed mitochondrial-peptide drugs.[3]
- Gray-market products. A 2026 sports medicine review warned that rigorous human safety data for unapproved peptides such as MOTS-c are scarce.[16]
What’s next
- 4TAZPower is the confirmatory elamipretide trial in Barth syndrome, recruiting about 48 patients with primary completion expected in September 2029.[13]
- ReNEW is a phase 3 trial of elamipretide injections in 313 people with dry age-related macular degeneration, with primary completion expected in August 2027.[14]
- MOTS-c regulation: in July 2026, FDA’s compounding advisory committee voted narrowly to recommend MOTS-c for the compounding list, against FDA staff advice. The vote is not binding.[15][5]
For related longevity research, see our comparisons of Epitalon vs TA-65 and peptides vs exosomes, and the profiles for NAD+ and epitalon. Anyone interested in these compounds should talk with a clinician, ideally about registered trials rather than unregulated products.
