Skip to content

Longevity

All peptides
Mitochondrial-derived peptide

MOTS-c

Also known as: Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc, Mitochondrial ORF of the 12S rRNA-c

Mitochondrial-encoded peptide with strong rodent data on insulin sensitivity, endurance, and metabolic health.

Reviewed 2026-05-04

What it does

MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene — one of the first mitochondrial-encoded peptides discovered. In rodents it improves insulin sensitivity, increases endurance capacity, reduces diet-induced obesity, and activates AMPK signaling. Plasma levels rise with exercise in humans. Community use targets metabolic health, longevity, and athletic recovery.

Used for

Dose

Starting
5,000 mcg · 2–3× per week
Common
7,500 mcg · 2–3× per week
Upper
10,000 mcg · 2–3× per week
When
MorningMitochondrial-derived exercise mimetic. Morning dosing aligns with peak diurnal mitochondrial activity. Avoid evening — the metabolic activation can disrupt sleep onset.
Site
subcutaneous

Need exact volumes? Open the peptide calculator →

⚠ Caution

  • Pregnancy and breastfeeding (no human safety data)
  • Active malignancy (no human oncology data; mitochondrial-signaling effects in cancer are an active research question)
  • Hypersensitivity to peptide excipients
  • Long-term use beyond ~12 weeks lacks any human safety characterization
  • Any use should be considered experimental; not available through any FDA-approved channel

Often stacked with

  • SS-31 (Elamipretide) — MOTS-c activates AMPK and nuclear metabolic programs via mitochondria-to-nucleus retrograde signaling; SS-31 stabilises inner-membrane cardiolipin and improves electron-transport-chain efficiency — complementary mitochondrial targets.

Your stack

Track this peptide in your protocol — dose, schedule, vials on hand, refill projection. Stays in your browser; no account needed.

Add to my stack

Use this peptide

Featured in protocols
Co-injection & overlap

Inject separately (do not co-mix): SS-31 (Elamipretide)

Reconstitution & storage

Lyophilized powder reconstituted with bacteriostatic water. A 10 mg vial in 2 mL BAC water = 5 mg/mL, so a 5 mg dose ≈ 1 mL = 100 units on a U-100 syringe. (Note: a 5 mg dose nearly fills a U-100 syringe — most users prefer either a smaller dose or a higher dilution.) Use the calculator to verify.

Storage. Lyophilized: refrigerate 2–8 °C; protect from light. Reconstituted: refrigerate 2–8 °C, use within 30 days based on general peptide stability data — no MOTS-c-specific stability study published.

Open the peptide calculator →

Monitoring & questions

Reported side effects
  • Injection site reactions
  • Fatigue or transient flu-like symptoms reported anecdotally
  • Possible transient hypoglycemia given the AMPK/insulin-sensitivity mechanism (theoretical; monitor in users with diabetes)
  • No characterized long-term human side-effect profile — flag explicitly
Biomarkers Juno tracks
FAQ (1)

Reference

How it works

Translocates to the nucleus under metabolic stress and modulates nuclear gene expression — a rare example of mitochondrial-to-nuclear retrograde signaling by a peptide. Activates AMPK, increases GLUT4 translocation in skeletal muscle, and modulates insulin signaling. Endogenous plasma MOTS-c declines with age and rises acutely with exercise.

Juno's take

MOTS-c is genuinely interesting biology — a peptide encoded within a mitochondrial gene that acts as a retrograde signal between mitochondria and the nucleus. The rodent work is solid. The human work is at the very beginning: small observational and dose-finding studies, plus mechanistic plasma-level measurements during exercise. There are no Phase 2 efficacy RCTs for any clinical indication, so community framing as a "mitochondrial peptide for athletic performance" is currently mechanism-extrapolation. Re-evaluate when a real human trial publishes.

EvidenceTier 3 — Animal / in vitro

Tiers are per indication. The same molecule can be Tier 1 for one use and Tier 4 for another — the tier reflects published literature, not community framing.

Insulin sensitivity / metabolic health

Tier 3high confidence

Multiple rodent studies (Lee et al. Cell Metabolism 2015 and follow-ons) show improved insulin sensitivity, attenuated diet-induced obesity, and improved glucose tolerance. One small human observational study correlates higher endogenous MOTS-c with better metabolic phenotypes, but no controlled exogenous-MOTS-c human RCT has tested the metabolic indication directly.

Lee C et al. 2015Ramanjaneya M et al. 2019

Exercise capacity / endurance

Tier 3high confidence

Rodent studies show MOTS-c administration improves endurance and exercise capacity in older mice (Reynolds et al. Nat Commun 2021). Human plasma-MOTS-c rises acutely with exercise, suggesting it's an exercise-responsive signaling peptide endogenously. No RCT has tested exogenous MOTS-c on human exercise endpoints.

Reynolds JC et al. 2021

Healthspan / longevity

Tier 3high confidence

Mitochondrial-derived peptides are an active longevity-research area. The strongest data is mechanistic and animal-model. No human longevity outcome data exist for MOTS-c. The claim 'MOTS-c extends healthspan in humans' is not supported by published evidence.

Lee C et al. 2015

Mitochondrial dysfunction / mitochondrial disease

Tier 4medium confidence

No published trials in mitochondrial disease populations. Mechanistic relevance is plausible but not validated. Anecdotal use exists in the rare-disease community but is not supported by primary literature.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Citations (3)
  1. [1]
    The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
    Lee C, Zeng J, Drew BG, et al. · Cell Metabolism · 2015 · PMID 25738459
    Foundational rodent metabolic-effect paper; primary anchor for the metabolic and longevity Tier 3 indications.
    View source
  2. [2]
    MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
    Reynolds JC, Lai RW, Woodhead JST, et al. · Nature Communications · 2021 · PMID 33514812
    Rodent endurance/exercise capacity evidence; anchor for the exercise indication.
    View source
  3. [3]
    Mitochondrial-derived peptides are down-regulated in diabetes subjects
    Ramanjaneya M, Bettahi I, Jerobin J, et al. · European Journal of Endocrinology · 2019 · PMID 30940803
    Human observational data linking endogenous MOTS-c to metabolic phenotype; provides indirect human relevance.
    View source