SS-31 (Elamipretide) is a mitochondria-targeted antioxidant tetrapeptide that concentrates in the inner mitochondrial membrane, protects cardiolipin, reduces ROS, and has completed Phase 2 clinical trials for heart failure and age-related disease.
This peptide profile is for research and educational purposes only. Not intended for human use or self-administration.
Overview
SS-31, also known as Elamipretide or MTP-131, is a cell-permeable, mitochondria-targeted tetrapeptide developed by Dr. Hazel Shen-Tu Szeto at Cornell. Its design exploits the high negative charge of the inner mitochondrial membrane (IMM) to concentrate the peptide precisely where mitochondrial dysfunction originates — at the IMM, where cardiolipin (a mitochondria-specific phospholipid critical for electron transport chain function) is found. By protecting cardiolipin and reducing mitochondrial ROS, SS-31 addresses the root cause of mitochondrial dysfunction in aging, ischemia-reperfusion injury, and metabolic disease. It has completed Phase 2 clinical trials in heart failure with preserved ejection fraction (HFpEF).
Mechanism of Action
SS-31 concentrates approximately 1,000-fold in the IMM due to the large membrane potential. It binds cardiolipin — a phospholipid unique to the IMM that is essential for organizing the electron transport chain complexes (I, III, IV) into super-complexes (respirasomes) for efficient ATP production. Cardiolipin oxidation during mitochondrial stress disrupts these super-complexes, dramatically reducing ATP output and increasing electron leak and ROS production. SS-31 protects cardiolipin from oxidation, preserves respiratory chain organization, reduces ROS generation, and inhibits cytochrome c peroxidase activity that would otherwise trigger apoptosis. It also prevents mitochondrial permeability transition pore (mPTP) opening — a key event in cell death following ischemia-reperfusion.
Key Research
SS-31 has an extensive published research base covering over 15 years of preclinical and clinical development. Szeto laboratory studies established cardiolipin protection as the primary mechanism. Preclinical studies showed dramatic protection against cardiac, renal, and neuronal ischemia-reperfusion injury. The SPARCL Phase 2 trial (HFpEF, N=89) demonstrated statistically significant improvements in exercise capacity and quality of life at 4 weeks of IV dosing. A skeletal muscle study showed restoration of mitochondrial function and improved exercise capacity in sedentary older adults after 8 days. Studies in aging rodents confirmed SS-31 restored mitochondrial morphology, reduced ROS, and improved physical function — results potentially applicable to human sarcopenia and frailty.
3–40 mg/day subcutaneously or IV (clinical trials)
Half-Life
~2–3 hours
Clinical research doses ranged from 0.005 to 0.25 mg/kg/day (subcutaneous) in Phase 1, with Phase 2 IV dosing at 4 mg/hour for 4 hours in cardiac trials. Research community subcutaneous protocols typically use 2–10 mg/day based on preclinical allometric scaling. Cycles of 4–8 weeks are common. As a targeted mitochondrial intervention, it pairs logically with other mitochondrial compounds (MOTS-c, Humanin) and with longevity peptides (Epithalon, GHK-Cu) in advanced anti-aging protocols.
Side effects summarized from animal studies and researcher community observations. Educational purposes only — not medical advice.
SS-31 is well tolerated across clinical trials. The most common adverse event is mild to moderate injection site reactions (pain, redness, swelling) at subcutaneous sites — these are manageable with site rotation. No significant systemic toxicity, organ dysfunction, or endocrine effects have been documented. In cardiac trial populations, no meaningful drug-drug interactions were identified. Because SS-31 reduces ROS throughout the body, it could theoretically reduce beneficial ROS signaling in some contexts (e.g., exercise adaptation) — though this has not been demonstrated clinically at research doses.
Storage & Handling
Store lyophilized SS-31 at -20°C for long-term storage, 2–8°C for short-term (up to 1 month). Reconstitute with sterile or bacteriostatic water. SS-31 is relatively stable in solution — store reconstituted at 2–8°C and use within 21 days. Protect from light and heat. As a tetrapeptide with modified amino acids, it is more stable than larger peptides but should still be handled carefully.
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