Library / Peptides / Longevity & Anti-Aging / MOTS-c
Emerging evidence · Grade B

MOTS-c

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c)
Evidence
Emerging
Route
Subcutaneous injection
Frequency
3-5x per week or daily
Category
Longevity & Anti-Aging
TL;DR
MOTS-c is a mitochondrial-derived peptide (MDP) encoded within the 12S rRNA gene of the mitochondrial genome. Discovered in 2015 by Changhan Lee's lab at USC, it has been described as an exercise mimetic due to its effects on AMPK activation, glucose metabolism, and fat oxidation.
Part 01 · How it works

Mechanism.

MOTS-c is a mitochondrial-derived peptide (MDP) encoded within the 12S rRNA gene of the mitochondrial genome. Discovered in 2015 by Changhan Lee's lab at USC, it has been described as an exercise mimetic due to its effects on AMPK activation, glucose metabolism, and fat oxidation. It is one of the first known mitochondrial-encoded peptides that acts as a signaling molecule regulating nuclear gene expression.

Think of MOTS-c as a fitness tracker that lives inside your mitochondria. When it senses your cells are under energy stress, it sends a signal to the cell's control center saying 'time to start burning fuel more efficiently' -- mimicking many of the metabolic responses normally produced by exercise.

Mechanism · technical
MOTS-c activates AMPK (AMP-activated protein kinase), the cell's master energy sensor, which promotes glucose uptake and fatty acid oxidation. It also regulates the folate-methionine cycle, affecting one-carbon metabolism and cellular stress responses. Under metabolic stress, MOTS-c translocates to the nucleus where it regulates adaptive nuclear gene expression through interactions with ARE-containing genes (antioxidant response elements).
Part 02 · Dosing & administration

How it's taken.

Values below describe how MOTS-c has been administered in published trials and labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.

Standard dose
5-10 mg/week
Subcutaneous injection · 3-5x per week or daily
Duration
4-8 weeks typical cycle

Mitochondrial-derived peptide. Acts as exercise mimetic via AMPK activation. No FDA-approved indication. Dosing based on early clinical research and published research protocols. Endogenously produced.

Need help with reconstitution?

Use the free peptide calculator for dilution, unit conversion, and injection volume.

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Part 03 · Safety

Side effects, rare serious events, who shouldn't.

Reported side effects
Limited human safety data is available. In the small human studies conducted, MOTS-c appeared well-tolerated. Animal studies have not revealed significant toxicity. As a naturally occurring peptide whose levels decline with age, it is considered to have a favorable theoretical safety profile, but long-term human data is lacking.
Absolute · do not use
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to MOTS-c or any component
×
Active malignancy (effects on cellular metabolism in cancer cells unknown)
Interactions
Metformin
Both activate AMPK pathway; theoretical additive metabolic effects and hypoglycemia risk
Moderate
Insulin
MOTS-c improves insulin sensitivity; may potentiate insulin effect and increase hypoglycemia risk
Moderate
Exercise mimetics (AICAR)
Additive AMPK activation; clinical significance unknown but theoretical excessive metabolic stress
Minor
Labs to monitor
Fasting Glucose & Insulin
Baseline and monthly
MOTS-c improves insulin sensitivity and glucose uptake
HbA1c
Baseline and every 3 months
Track glycemic improvements
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Liver and kidney function
CK (Creatine Kinase)
Baseline and at 4 weeks
Exercise mimetic effects — monitor muscle stress
Lactate
Baseline (optional)
MOTS-c affects AICAR and AMPK pathway, altering energy metabolism
Part 04 · Research log

Every study we cite.

Each study with its published finding and a plain-language note on limitations or funding.

01
2020
0
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline
MOTS-c improved physical performance in aged mice and translocated to the nucleus during exercise stress
Preclinical; well-designed; Lee lab (discoverers)
PMID 32017880 ↗
02
2015
0
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis
MOTS-c prevented age-dependent and HFD-induced insulin resistance and obesity in mice
Discovery paper; landmark preclinical work
PMID 25738459 ↗
Part 05 · Cost & access

Where you can get it.

Regulatory status
MOTS-c is not FDA-approved for any indication. It is available through some compounding pharmacies and as a research chemical. It is not a controlled substance but has no regulatory approval for therapeutic use.
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Part 06 · Your appointment

Questions to bring.

01
What is my current metabolic health baseline (fasting glucose, insulin, HbA1c)?
02
How does MOTS-c compare to lifestyle interventions for metabolic improvement?
03
Are there any contraindications given my current medications?
04
What dosing protocols have been used in the available human studies?