MOTS-c
Mitochondrial Open Reading Frame of the 12S rRNA type-c · MOTSc · Mitochondrial-derived peptide MOTS-c
Mitochondrial-encoded peptide studied for insulin sensitivity and exercise capacity.
Typical dose
5 mg
3x per week
Range
2.5–10
mg
Half-life
—
see Dosing
Evidence
Animal only
Subcutaneous · Intramuscular
What it is
MOTS-c is a 16-amino-acid peptide encoded inside the mitochondrial genome rather than the nuclear one, discovered by the Cohen lab at USC in 2015. It is one of a small family of mitochondrial-derived peptides that appear to act as signals from the mitochondria to the rest of the cell, telling the nucleus how metabolic supply is holding up.
The animal data is genuinely interesting. In mice, injected MOTS-c prevented diet-induced obesity and insulin resistance, and in older mice it improved running capacity and physical performance. Endogenous MOTS-c rises in human skeletal muscle and plasma with exercise, and declines with age, which is the observation the whole longevity interest is built on.
What does not exist is a controlled human trial of injected MOTS-c. Every human data point is observational — measuring what the body already makes — not testing what happens when you inject it. Community dosing is extrapolated from mouse work and forum reports, so treat the numbers below as convention rather than validated therapy.
How it works
MOTS-c translocates to the cell nucleus under metabolic stress and acts on antioxidant response element genes, while in the cytosol it interferes with the folate-methionine cycle. The resulting build-up of AICAR activates AMPK, the same energy-sensing switch that metformin and exercise hit, which pushes cells toward glucose uptake, fatty acid oxidation and away from storage.
Practically, that means MOTS-c behaves like an exercise-mimetic signal rather than a hormone. It does not add anabolic drive, raise IGF-1, or blunt appetite; the effect people chase is better fuel handling and work capacity, which is why it is most often run alongside training rather than instead of it.
Dosing
Total weekly exposure matters more than per-shot size — on the 3x/week schedule above the 2.5-10 mg per-shot range works out to 7.5-30 mg per week, with most protocols landing near 15 mg. There is no human dose-finding data, so start at the low end and hold there for a full cycle before escalating.
Reconstitution calculator
Pre-loaded with MOTS-c’s vial size, water volume and typical dose. Change anything.
Typical: 5 mg · range 2.5–10
Draw to
100 u
1 mL · 5 mg
Concentration
5 mg/mL
50 mcg per unit
Doses per vial
1
Vial lasts
2.3 days
CheckThe draw fills more than 90% of the barrel. Workable, but there is no room for an air bubble or a correction.
Once mixed
Refrigerate at 2-8 C, protect from light, use within about 30 days; do not freeze once in solution.
1 mL of bacteriostatic water into a 5 mg vial gives 5 mg/mL, so a 5 mg dose is the full 1 mL (100 units on a U-100 insulin syringe); into a 10 mg vial the same 1 mL gives 10 mg/mL and 5 mg is 0.5 mL (50 units). Aim the water down the vial wall and swirl gently; MOTS-c is a small peptide but shaking still risks aggregation.
Storage
Before mixing
Refrigerated at 2-8 C the sealed powder holds for 18-24 months; freezing at -20 C extends that but is not necessary.
After mixing
Refrigerate at 2-8 C, protect from light, use within about 30 days; do not freeze once in solution.
Reported benefits
- ▪Improved insulin sensitivity and glucose disposal in rodent models
- ▪Prevented diet-induced obesity in mice without food restriction
- ▪Restored running capacity and physical performance in aged mice
- ▪Activates AMPK, the same energy-sensing pathway as exercise and metformin
- ▪Users commonly report better work capacity and reduced training fatigue
- ▪No anabolic or appetite effect, so it stacks cleanly with other compounds
Side effects
- ▪Injection-site redness, itching or a raised wheal — the most frequently reported issue
- ▪Flushing or a warm sensation in the first 10-20 minutes after injection
- ▪Stimulation and disrupted sleep if dosed in the evening
- ▪Headache or lightheadedness, usually at the higher end of the dose range
- ▪Possible additive blood-glucose lowering alongside insulin, metformin or a GLP-1
- ▪Long-term safety in humans is entirely unknown — there is no chronic exposure data
Do not use if
- ▪Use with insulin or sulfonylureas without glucose monitoring, given the additive hypoglycaemia risk
- ▪Pregnancy and breastfeeding — no data
- ▪Known hypersensitivity to the peptide or to benzyl alcohol in bacteriostatic water
Evidence level — Animal only
Preclinical animal data — no meaningful human trials.
Not FDA-approved for any indication; sold as a research chemical in most markets.
Commonly run with
SS-31
Cardiolipin-binding mitochondrial peptide, FDA-approved as elamipretide for Barth syndrome.
10 mg · Once daily
Humanin
First mitochondrial-derived peptide discovered, studied for cytoprotection and metabolism.
1 mg · 3x per week
Epitalon
Pineal-derived tetrapeptide studied for telomerase activation and circadian regulation.
10 mg · Once daily during a course
5-Amino-1MQ
Oral NNMT inhibitor aimed at fat-cell metabolism and NAD+ salvage. Mouse data only.
100 mg · once daily
MOTS-c FAQ
Is MOTS-c a fat-loss peptide?+
Not directly. It improves how cells handle glucose and fatty acids, which can support a deficit, but it does not suppress appetite or mobilise fat the way a GLP-1 or a beta-agonist does. Mice on it stayed lean on a bad diet; humans in a surplus will still gain.
How long until I notice anything?+
Most people who report an effect describe it in the second or third week, usually as work capacity or recovery rather than anything acute. If four weeks at a reasonable dose produce nothing, escalating further is unlikely to change that.
Why do doses vary so wildly online, from 200 mcg to 10 mg?+
Because there is no human dose-finding trial to anchor them. The low figures are often scaled directly off mouse doses, the high figures come from forum practice. The 5-10 mg range is where community consensus has settled, not where evidence points.
Does it need to be cycled?+
There is no receptor-downregulation mechanism identified that would force a break, so cycling is precautionary rather than pharmacological. Running 4-8 weeks on and a similar period off keeps chronic exposure limited in a compound with no long-term human safety data.
References
- 1.The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance — Cell Metabolism (2015) PMID 25738459
- 2.MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis — Nature Communications (2021) PMID 33473109
- 3.Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers — Aging (Albany NY) (2016) PMID 27070352
More longevity & mitochondrial
Epitalon
Pineal-derived tetrapeptide studied for telomerase activation and circadian regulation.
10 mg · Once daily during a course
Humanin
First mitochondrial-derived peptide discovered, studied for cytoprotection and metabolism.
1 mg · 3x per week
SS-31
Cardiolipin-binding mitochondrial peptide, FDA-approved as elamipretide for Barth syndrome.
10 mg · Once daily