what is the difference
MOTS-c and humanin
Two peptides encoded by the mitochondrion's own DNA, with registry counts that describe measurement programmes rather than treatment programmes.
MOTS-c is a sixteen amino acid peptide encoded inside the mitochondrial 12S ribosomal RNA gene. Humanin is a 24 amino acid peptide encoded inside the 16S ribosomal RNA gene of the same mitochondrial genome. Both are written by the organelle's own DNA rather than by the DNA in the cell nucleus, which is the genuinely novel piece of biology behind either of them: a compartment inside the cell encoding a signalling peptide that acts outside itself.
They are sold on that shared reasoning, usually under the heading of mitochondrial or longevity peptides, and they arrive with a number attached. A registry search returns 9 registrations for MOTS-c and 7 for humanin, checked on 2 August 2026. Reading what those 16 records actually are is the whole of this page, and it is a different exercise from reading their titles.
Not medical advice
This page reports what has been documented about a compound. It is not medical advice, not a diagnosis, not a dosing protocol, and not a recommendation to obtain or use anything described here. Talk to a licensed clinician about anything concerning your health. Read the full disclaimer.
Reviewed against editorial standards Updated
The short answer
Of the 16 registrations across both compounds, one administers the peptide. It is a phase 2 study of MOTS-c in adults with prediabetes and overweight or obesity, NCT07505745, which was recruiting on 2 August 2026 with nothing posted. Every other record measures how much of the peptide a person already makes, as a marker inside a study about something else.
Both peptides occur naturally in the body, which is why so much clinical research measures them. A study that draws blood and reports a concentration appears in a registry search under the compound's name and administers nothing. Counting those records as trials is the error this page exists to name.
Side by side
| Property | MOTS-c | Humanin |
|---|---|---|
| Length | 16 amino acids | 24 amino acids |
| Where it is encoded | Inside the mitochondrial 12S ribosomal RNA gene | Inside the mitochondrial 16S ribosomal RNA gene |
| Analog names in circulation | None widely used. The name refers to one sequence | S14G-humanin, usually written HNG, which is a different sequence sold under the same heading |
| Founding paper | Cell Metabolism, 2015, reporting effects on measures of insulin sensitivity and fat mass in mice and tracing them to a folate and AMPK pathway | Proceedings of the National Academy of Sciences, 2001, from a screen for factors keeping nerve cells alive under Alzheimer's-related insults, in cultured cells |
| Registrations on ClinicalTrials.gov | 9 | 7 |
| Registrations that give the peptide to anyone | 1, NCT07505745, phase 2 in adults with prediabetes and overweight or obesity, recruiting with nothing posted | 0 |
| What the rest of the registrations do | Measure the body's own MOTS-c as a marker: exercise after a breast cancer diagnosis, anaesthesia technique, diabetes and coronary disease, fasting, dialysis, deafness screening, vestibular implants | Measure the body's own humanin as a marker: cardiac surgery, acute kidney injury, IVF in polycystic ovary syndrome, muscle biopsies in cerebral palsy, plus two studies where it is one readout among several |
| What the human numbers describe | How much MOTS-c people have and how that changes, including a rise in circulating mitochondrial-derived peptides after endurance exercise | How much humanin people have, including a rise in plasma and muscle after high-intensity interval exercise, and its behaviour as a candidate biomarker |
| WADA 2026 Prohibited List | Named on the face of the list at S4.4.1, the class covering AMPK activators, prohibited at all times | Not named on the list |
| FDA Pharmacy Compounding Advisory Committee, 23 and 24 July 2026 | One of the seven substances put to a vote, in separate questions on the free base and the acetate. FDA has published no vote record, and the 503A record on this site sets out the meeting | Not among the seven |
| Approval status | None anywhere | None anywhere |
Why the two get mixed up
The two are marketed together because the biology genuinely pairs them. Both belong to a small set of peptides encoded by mitochondrial DNA, described in the literature as mitochondrial-derived peptides or mitokines, and reviews cover them in the same paper [7]. A reader meeting one of them meets the other in the next paragraph, and the shared origin does real work in the sales pitch.
What travels with that pairing is the registry number, and the number is where the reading goes wrong. Both peptides are made by the human body, so researchers measure them the way they measure any other circulating marker: in cardiac surgery patients, in dialysis patients, in people fasting, in athletes before and after exercise. Every one of those studies is registered under the peptide's name and administers nothing. Nine registrations reads like a development programme. Eight of the nine are blood draws inside somebody else's study.
The third piece is the analog. Humanin's more potent laboratory version, S14G-humanin, is usually written HNG, and product listings use the two names interchangeably even though they are different sequences. Animal work often cited for humanin was run on the analog rather than on the natural peptide [8], which is the same fragment-and-parent problem that runs through this catalog, one layer further in.
What the published record covers for each
The preclinical work behind both is real and it is preclinical. The 2015 founding paper reported that MOTS-c given to mice changed measures of insulin sensitivity and fat mass, and traced the effect to a folate and AMPK pathway [Animal] [1]. The 2001 paper that described humanin came out of a screen in cultured nerve cells challenged with amyloid and with familial Alzheimer's mutations, where the peptide in the medium changed survival [In-vitro] [4]. Work on the humanin analog HNG in male mice reported effects on germ cells and leucocytes during chemotherapy [Animal] [8].
What this evidence can and cannot show. These results come from mice and from cultured nerve cells, not from people. An animal model is a deliberate simplification: the injury is created on purpose, the animal is young and healthy, the amount given is scaled to body weight in a way that does not translate directly, and the outcome is measured at a fixed point rather than lived with. Cell and tissue work is a further step removed, because the concentrations that produce an effect in a dish are often far above anything a body reaches. Mechanism is a reason to run a trial. It is not a substitute for one, and compounds that looked mechanistically convincing have failed in people many times.
The human numbers that do exist are measurements of what people already have. A randomised study published in 2021 reported that circulating mitochondrial-derived peptides rise after acute endurance exercise in people who were given no peptide at all [Human RCT] [2]. A second randomised exercise study, in Hispanic and non-Hispanic white breast cancer survivors, used MOTS-c as one of its measured outcomes and likewise administered none [Human RCT] [3]. Both carry a randomised tier because that is what their design was: the randomisation was of an exercise programme, and the peptide is the readout.
On the humanin side, levels rose in plasma and in muscle after high-intensity interval exercise in men, again with nothing administered [Human open-label] [5]. A 2025 study examined humanin and MOTS-c expression alongside telomere length as candidate biomarkers in Alzheimer's disease [Human open-label] [6]. Each of those describes what the body does with its own supply. None of them says anything about what follows when the peptide is supplied from outside.
The regulatory positions are where the two come apart, and the gap reflects attention rather than evidence. MOTS-c is named on the face of the 2026 WADA Prohibited List at S4.4.1, the class covering AMPK activators, and that class is prohibited at all times rather than in competition only [9]. It was also one of the seven substances FDA put to its Pharmacy Compounding Advisory Committee on 23 and 24 July 2026, in separate votes on the free base and the acetate, and FDA has published no vote record [10]. Reporting says the committee recommended MOTS-c for inclusion, against FDA staff's own written proposal, and the 503A record on this site sets out what that did and did not change. Humanin appears in neither document. Reading that difference as a safety signal in either direction would be a mistake: it records which compound regulators have looked at, not what either one does.
Our takeSixteen registrations across the pair, and one of them gives anybody the peptide. The rest are blood tests. That is the single most useful thing to know about either compound, and it is invisible from a registry count.
Frequently asked questions
Are MOTS-c and humanin the same kind of thing?
They are two different peptides that share an unusual origin. MOTS-c is 16 amino acids encoded inside the mitochondrial 12S ribosomal RNA gene, humanin is 24 amino acids encoded inside the 16S gene, and both are written by mitochondrial DNA rather than by the nucleus. The literature groups them as mitochondrial-derived peptides [7]. That is a shared address in the genome, not a shared evidence base.
Does MOTS-c have nine clinical trials?
It has nine registrations. Eight of them measure the body's own MOTS-c as a marker inside studies about exercise, anaesthesia, diabetes, fasting, dialysis and other topics. One administers it: NCT07505745, a phase 2 study in adults with prediabetes and overweight or obesity, which was recruiting on 2 August 2026 with nothing posted.
Has humanin been given to anyone in a study?
Not in any registered or published study this site found. All seven registrations returned on 2 August 2026 measure the humanin a person already makes, in cardiac surgery, acute kidney injury, IVF, muscle biopsy and exercise research. The work behind the marketing is cell and animal work [4] [8].
What do the exercise studies actually show?
That levels of these peptides in blood and muscle change after exercise in people who were given none. A randomised study reported a rise in circulating mitochondrial-derived peptides after acute endurance exercise [2], and a separate study reported a rise in humanin in plasma and muscle after high-intensity interval training in men [5]. Both describe the body's own supply rather than anything supplied from outside.
Is either one banned in sport?
MOTS-c is named on the face of the 2026 WADA Prohibited List at S4.4.1, the class covering AMPK activators, and that class is prohibited at all times rather than in competition only [9]. Humanin is not named on the list, though the S0 catch-all covers substances with no current approval for human therapeutic use whether or not they are named.
What is HNG, and is it the same as humanin?
HNG is S14G-humanin, a laboratory analog with a single amino acid substitution, reported as more potent than the natural peptide. It is a different sequence, and product listings use the two names interchangeably. Much of the animal work cited for humanin was run on the analog rather than on the natural peptide [8], which is worth knowing before reading a result as being about either one.
References
- Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015. PMID 25738459 DOI 10.1016/j.cmet.2015.02.009
- von Walden F, Fernandez-Gonzalo R, Norrbom J, Emanuelsson EB, Figueiredo VC, Gidlund EK, Norrbrand L, Liu C, Sandström P, Hansson B, Wan J, Cohen P, Alkner B. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985). 2021. PMID 34351816 DOI 10.1152/japplphysiol.00706.2019
- Dieli-Conwright CM, Sami N, Norris MK, Wan J, Kumagai H, Kim SJ, Cohen P. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Sci Rep. 2021. PMID 34413391 DOI 10.1038/s41598-021-96419-z
- Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001. PMID 11371646 DOI 10.1073/pnas.101133498
- Woodhead JST, D'Souza RF, Hedges CP, Wan J, Berridge MV, Cameron-Smith D, Cohen P, Hickey AJR, Mitchell CJ, Merry TL. High-intensity interval exercise increases humanin, a mitochondrial encoded peptide, in the plasma and muscle of men. J Appl Physiol (1985). 2020. PMID 32271093 DOI 10.1152/japplphysiol.00032.2020
- Rodríguez-Esparragón F, Cazorla-Rivero SE, Torrealba E, Cánovas-Molina Á, González-Hernández AN, Martín-Alfaro R, Afonso-Medina MP, Martínez de Saavedra-Álvarez MT, Pérez-Santana CG, Bartolomé C, Estupiñán L, González-Martín JM, Clavo B. Insights into the Biomarker Potential of Humanin and Mots-c Expression and Telomere Length in Alzheimer's Disease. Int J Mol Sci. 2025. PMID 41303353 DOI 10.3390/ijms262210866
- Miller B, Kim SJ, Kumagai H, Yen K, Cohen P. Mitochondria-derived peptides in aging and healthspan. J Clin Invest. 2022. PMID 35499074 DOI 10.1172/JCI158449
- Lue Y, Swerdloff R, Wan J, Xiao J, French S, Atienza V, Canela V, Bruhn KW, Stone B, Jia Y, Cohen P, Wang C. The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice. Endocrinology. 2015. PMID 26384090 DOI 10.1210/en.2015-1542
- World Anti-Doping Agency. The 2026 Prohibited List, international standard, effective 1 January 2026. MOTS-c is named at S4.4.1, the AMPK activator class. WADA. 2026. Source document
- US Food and Drug Administration. Questions for PCAC regarding whether FDA should include certain bulk drug substances on the 503A Bulks List, Pharmacy Compounding Advisory Committee, 23 and 24 July 2026. The document names all seven substances put to a vote: BPC-157, KPV, TB-500, MOTS-c, emideltide, epitalon and semax. FDA advisory committee materials. 2026. Source document