SS-31 // Mitochondrial Shield
A cell-permeable tetrapeptide that concentrates 5,000x in the inner mitochondrial membrane, binding cardiolipin to optimize electron transport chain efficiency and reduce reactive oxygen species production. Currently in Phase 3 clinical trials for heart failure. The most advanced mitochondrial-targeted compound in clinical development.
Repairing the cell's power plant.
Mitochondria produce 90% of your cellular energy. With age, the inner mitochondrial membrane deteriorates — cardiolipin becomes oxidized, electron transport chain efficiency drops, and ROS production increases. SS-31 reverses this decline at the membrane level.
Daily dosing, continuous protocol.
SS-31 uses continuous daily dosing — the mitochondrial membrane protection is maintained through sustained peptide presence. The Phase 3 clinical trial dose of 40mg/day subcutaneous is the reference standard.
From Szeto-Schiller to Phase 3.
SS-31 was developed by Hazel Szeto and Peter Bhatt at Weill Cornell Medicine. The Szeto-Schiller peptide motif — an alternating aromatic-cationic structure — enables cell membrane penetration and extreme mitochondrial concentration without requiring a targeting sequence.
Preclinical data demonstrated that SS-31 restored mitochondrial function in aged tissues, improved cardiac ejection fraction, reduced ischemia-reperfusion injury, and enhanced skeletal muscle performance. The compound acts by stabilizing cardiolipin-dependent cristae structure.
Phase 2 trials in heart failure with preserved ejection fraction (HFpEF) and Barth syndrome showed improvements in cardiac function markers. Phase 3 trials are ongoing. Additional investigations include primary mitochondrial myopathy, age-related macular degeneration, and renal injury.
Mitochondrial compounds compared.
| Compound | Target | Mechanism | Route | Stage |
|---|---|---|---|---|
| SS-31 | Inner Mito Membrane | Cardiolipin Binding | SubQ daily | Phase 3 |
| MOTS-C | AMPK / Nucleus | Metabolic Signaling | SubQ 3–5x/week | Research |
| CoQ10 | Complex III | Electron Carrier | Oral daily | Supplement |
| MitoQ | Mitochondrial Matrix | Antioxidant | Oral daily | Supplement |
What to watch for.
SS-31's side effect profile is manageable with proper protocol adherence. Baseline blood work before starting and periodic monitoring during use is essential.
- Injection site reactions (most common in trials)
- Headache (mild, comparable to placebo in some trials)
- Nausea (uncommon)
- Generally well tolerated in Phase 2/3 data
- No significant safety signals at clinical doses
- Cardiac monitoring recommended (compound targets heart mitochondria)
- Cardiac biomarkers (BNP/NT-proBNP, troponin)
- Echocardiogram (ejection fraction — if cardiac indication)
- Lactate (mitochondrial function marker)
- CoQ10 levels
- Comprehensive metabolic panel
- Complete blood count
- hsCRP (inflammation)
- Creatine kinase (muscle mitochondrial marker)
- MOTS-C for comprehensive mitochondrial longevity (Anti-Aging Stack)
- Epithalon for telomere + mitochondrial dual targeting
- NAD+/NMN for NAD+ restoration alongside ETC optimization
- CoQ10 is complementary (different mito target)
- Exercise amplifies mitochondrial biogenesis from SS-31
- Monitor cardiac markers if history of heart disease
- Lyophilized: refrigerate at 2–8°C (36–46°F)
- Reconstituted: refrigerate, use within 21 days
- Protect from light
- Do not freeze reconstituted solution
- Tetrapeptide — relatively stable
Compounds that complement SS-31.
The most clinically advanced mitochondrial therapy — and it's still investigational.
SS-31 has something most longevity peptides lack: Phase 3 clinical trial data. The cardiolipin-binding mechanism is elegant, the 5,000x mitochondrial concentration is unmatched, and the clinical results in heart failure are promising. For longevity purposes, SS-31 addresses the mitochondrial membrane deterioration that drives cellular energy decline with age. Stack with MOTS-C (AMPK activation) and Epithalon (telomere protection) for the complete Anti-Aging Stack. The daily injection protocol requires commitment, but mitochondrial function is the foundation everything else — cognition, energy, recovery, longevity — depends on.
Our free Protocol Guide includes the complete Anti-Aging Stack — SS-31, MOTS-C, Epithalon with cardiac monitoring, mitochondrial biomarkers, and tracking templates.