Comparison
MOTS-c vs Sermorelin
Side-by-side of MOTS-c and Sermorelin. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
Sermorelin
Sermorelin peptide therapy uses a 29-amino-acid GHRH analog to raise endogenous GH. Dosing, half-life, sermorelin vs ipamorelin, and safety.
Effects at a glance
MOTS-c
- •16-amino-acid peptide encoded in mitochondrial DNA (12S rRNA region); discovered 2015
- •Activates AMPK in skeletal muscle and liver; improves insulin sensitivity in rodent models
- •Circulating endogenous levels decline with age, motivating the longevity-restoration hypothesis
- •CohBar's MOTS-c analog CB4211 discontinued after phase 1b NASH readout did not meet endpoints
- •Anecdotal protocols use 5 to 10 mg subcutaneously 2 to 3 times weekly
- •Not on the WADA Prohibited List as of 2026; future scrutiny likely given exercise-mimetic mechanism
Sermorelin
- •Synthetic 29-amino-acid GHRH fragment; FDA approved 1997 for pediatric GH deficiency as Geref
- •Voluntarily discontinued by Serono in 2008 for commercial reasons; not safety-related
- •Compounded by 503A/503B pharmacies for off-label adult anti-aging and body-composition use
- •Produces physiologic pulsatile GH release; ~10 to 20 minute plasma half-life
- •Standard anti-aging clinic protocol: 200 to 500 mcg subcutaneously pre-bed, often with ipamorelin
- •Banned by WADA under S2 (peptide hormones, growth factors)
Side-by-side
| Attribute | MOTS-c | Sermorelin |
|---|---|---|
| Category | peptide | peptide |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | Sermorelin acetate, GRF 1-29, Geref, GHRH (1-29) NH2 |
| Half-life (hr) ↗ | 0.5 | 0.25 |
| Typical dose (mg) ↗ | 5 | 0.3 |
| Dosing frequency | 2-3x weekly | 1-2x daily |
| Routes | subcutaneous | subcutaneous |
| Onset (hr) | 1 | 0.25 |
| Peak (hr) | 4 | 0.5 |
| Molecular weight | 1880.18 | 3357.88 |
| Molecular formula | C82H132N22O25S2 | C149H246N44O42S |
| Mechanism | Mitochondrial-derived peptide that activates AMPK in skeletal muscle and liver, improves insulin sensitivity, and translocates to the nucleus under metabolic stress to modulate nuclear gene expression in retrograde mitochondrial signaling. | Synthetic 29-amino-acid GHRH fragment that binds the GHRH receptor on pituitary somatotrophs to stimulate endogenous pulsatile GH synthesis and release while preserving the GH-IGF-1 negative feedback loop. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | FDA approved 1997 (Geref, pediatric GHD); voluntarily discontinued by Serono 2008; compounded by 503A/503B pharmacies for off-label adult use; banned by WADA |
| WADA status | unknown | banned |
| DEA / Rx | Not scheduled (research chemical) | Rx only via compounding (no controlled-substance schedule) |
| Pregnancy | Insufficient data; not recommended | Category C (historical labeling); not recommended in pregnancy |
| CAS | 1627580-64-6 | 86168-78-7 |
| PubChem CID | 139599184 | 16129617 |
| Wikidata | Q24832108 | Q416620 |
Safety profile
MOTS-c
Common side effects
- injection-site irritation
- transient fatigue
- headache (anecdotal)
Contraindications
- pregnancy
- lactation
- active malignancy (theoretical)
- severe hypoglycemia risk on concurrent insulin or sulfonylurea
Interactions
- insulin: additive insulin sensitization may increase hypoglycemia risk(moderate)
- metformin: both activate AMPK; theoretical additive metabolic effect, no controlled data(minor)
- sulfonylureas: increased hypoglycemia risk via additive insulin sensitization(moderate)
Sermorelin
Common side effects
- injection-site pain or irritation
- transient flushing
- headache
- vivid dreams (pre-bed dosing)
Contraindications
- pregnancy
- active malignancy
- history of pituitary tumor
- diabetic retinopathy (theoretical)
- untreated hypothyroidism
Interactions
- ipamorelin: synergistic GH release via parallel GHRH and ghrelin pathways; standard anti-aging clinic pairing(minor)
- CJC-1295: pharmacologically redundant (both GHRH-pathway); typically not stacked(minor)
- insulin: sustained GH can blunt insulin sensitivity over weeks(moderate)
- corticosteroids: blunt GH response; reduce expected efficacy(moderate)
- levothyroxine (untreated hypothyroidism): untreated hypothyroidism blunts GH response; correct thyroid first(moderate)
Which Should You Take?
Sermorelin comes out ahead for most readers on the criteria we weight: 3 catalogued goals, FDA approved 1997 (Geref, pediatric GHD); voluntarily discontinued by Serono 2008; compounded by 503A/503B pharmacies for off-label adult use; banned by WADA, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
- → If your priority is mitochondrial function, pick MOTS-c.
- → If your priority is growth-hormone axis, pick Sermorelin.
- → If your priority is post-training recovery, pick Sermorelin.
Default choice: Sermorelin. Wider use case, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for MOTS-c only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between MOTS-c and Sermorelin?
MOTS-c and Sermorelin differ in category (peptide vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, MOTS-c or Sermorelin?
MOTS-c half-life is 0.5 hours; Sermorelin half-life is 0.25 hours.
Can you stack MOTS-c with Sermorelin?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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