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Longevity

MOTS-c

Mitochondrial-derived peptide encoded in mitochondrial DNA, studied for metabolic regulation and exercise-mimetic effects.

Research chemical Longevity Fitness & muscle

Reviewed 2026-09-12
Full name
Mitochondrial Open Reading Frame of the 12S rRNA-c
Also known as
MOTS-c
Regulatory status
Research chemical, no clinical approval. Human evidence is essentially nonexistent; almost all data is from rodent studies.

Origin

Discovered in 2015. Unusual among peptides here: it's encoded not by nuclear DNA but within the mitochondrial genome, in the 12S ribosomal RNA region, and appears to signal mitochondrial status to the rest of the cell and body.

Mechanism

In animal studies, MOTS-c activates AMPK, the energy-sensing pathway also triggered by exercise and caloric restriction, and moves to the nucleus under metabolic stress to regulate genes for glucose metabolism and antioxidant response. This exercise-mimetic mechanism drives interest in it for metabolic health and longevity.

Research summary

Evidence

Mouse studies show MOTS-c can prevent age-dependent and diet-induced insulin resistance, improve exercise capacity, and in some studies extend healthspan markers in older mice. Circulating MOTS-c in humans declines with age and rises with exercise, the correlational basis for its 'exercise-in-a-vial' reputation. No published human interventional trials of injected MOTS-c exist. Early-stage, more hypothesis than validated therapy.

Evidence tier: Research chemical — see the methodology note for how this is assessed.

Citations

Reported benefits

  • Reported by users as supporting exercise capacity and recovery
  • Interest for metabolic health/insulin sensitivity support
  • Often stacked with other longevity peptides (Epithalon, NAD+) despite having a distinct, muscle/metabolism-focused mechanism

Dosing protocols reported in the literature & community

These are protocols reported by compounding pharmacies, published trials, or self-experimentation communities — not a prescription. Start low, especially for anything new.

Reported dosing protocols
RouteReported protocol
Subcutaneous injectionCommon community-reported protocol is roughly 5-10 mg per week, split across 2-3 injections, often cycled in blocks of several weeks with breaks. No human dose-finding trial exists, so treat any specific number as convention, not evidence-based dosing.

Side effects

  • Injection-site reactions reported
  • No systematic human safety data exists at any dose

Safety notes

Safety: One of the least human-validated compounds in this wiki. The mouse mechanism is genuinely interesting to metabolic-disease researchers, but there's a large gap between promising mouse data and a known-safe, known-effective human compound.
Community & reddit notes (anecdotal — not clinical evidence)

Popular in longevity stacks alongside Epithalon and NAD+, usually framed around metabolic health and exercise capacity rather than tissue repair. Discussion skews speculative and mechanism-focused rather than experience-report-focused, unlike BPC-157, reflecting how new and understudied it is.

Mixing compatibility

Pulled from a community-charted mixing-compatibility reference (anecdotal, clinic-use, and community-reported signals) — not a safety guarantee. Verify independently before combining anything.

Used together in wellness-clinic protocols

Reported as a combination to avoid