SS-31 (also known as elamipretide, Bendavia, or MTP-131) is a synthetic tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) that selectively concentrates in the inner mitochondrial membrane, where it reduces oxidative damage to cardiolipin — a phospholipid critical for mitochondrial cristae architecture and the efficiency of the electron transport chain. SS-31 has reached Phase II and Phase III clinical trials for heart failure and the rare mitochondrial disease Barth syndrome, giving it an unusually strong clinical development record for a research peptide. Its anti-aging relevance stems from mitochondrial dysfunction's central role in the hallmarks of aging.
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SS-31 (elamipretide, MTP-131) is a synthetic tetrapeptide that targets the inner mitochondrial membrane. Full guide to its mechanism, clinical trial results, dosing, and anti-aging applications.
How Does SS-31 Work?
Cardiolipin is a unique phospholipid found almost exclusively in the inner mitochondrial membrane (IMM), where it plays a critical structural role in organising the electron transport chain (ETC) supercomplexes that produce ATP. With aging and oxidative stress, cardiolipin undergoes peroxidation — its polyunsaturated fatty acid chains are damaged by reactive oxygen species (ROS), disrupting ETC supercomplex structure and reducing mitochondrial membrane potential.
SS-31 interacts with cardiolipin through electrostatic and hydrophobic forces, concentrating in the IMM at a 1,000-fold enrichment over cytoplasmic concentration. This physical association protects cardiolipin from peroxidation, preserves ETC supercomplex integrity, restores mitochondrial membrane potential, and reduces ROS generation — a positive feedback where reduced ROS production leads to less cardiolipin damage, which leads to further ROS reduction. The result is substantially improved mitochondrial bioenergetics in tissues where mitochondrial dysfunction is driving pathology.
Clinical Trial Results
The HOPEFUL-1 trial (Phase IIb in heart failure) showed SS-31 (elamipretide) improving 6-minute walk distance and patient-reported quality of life in heart failure with reduced ejection fraction. The EVOLUTION-HF Phase III trial is ongoing. In Barth syndrome (a rare mitochondrial cardiomyopathy caused by tafazzin mutation disrupting cardiolipin), SS-31 produced significant improvements in skeletal muscle function and quality of life in a Phase III trial — representing a rare treatment success in a genetically defined mitochondrial disease.
Beyond cardiovascular applications, animal studies show SS-31 reversing age-related declines in skeletal muscle mitochondrial function, physical capacity (wheel running in old mice significantly improved to near-young levels), and kidney function after ischemia-reperfusion injury. These results in aged animals are the primary basis for SS-31's use in longevity research contexts.
Anti-Aging and Longevity Applications
The mitochondrial theory of aging — that accumulating mitochondrial dysfunction drives the broad aging phenotype — positions SS-31 as a theoretically powerful longevity intervention. If cardiolipin peroxidation is a key driver of the mitochondrial dysfunction that accumulates with age, then cardiolipin protection with SS-31 should attenuate this driver.
Research use for anti-aging and performance typically involves: daily or every-other-day subcutaneous injections at 1–3 mg per dose, in 8–12 week cycles. Community users report improved exercise performance, recovery, and a subjective sense of "cellular energy" consistent with improved mitochondrial bioenergetics. No long-term human safety data outside clinical trials exists, but the clinical trial safety record (heart failure and Barth syndrome populations over months) is reassuring.
SS-31 Research Profile
| Parameter | Dose | Route | Frequency | Notes |
|---|---|---|---|---|
| Other names | Elamipretide, Bendavia, MTP-131 | — | — | — |
| Mechanism | Cardiolipin protection → ETC integrity | — | — | — |
| Research dose | 1–3 mg/day SubQ | — | — | — |
| Cycle length | 8–12 weeks | — | — | — |
| Clinical stage | Phase II/III (heart failure, Barth syndrome) | — | — | — |
| Human safety data | Yes — from clinical trials | — | — | — |
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Frequently Asked Questions
Yes — SS-31, elamipretide, Bendavia, and MTP-131 are all names for the same tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2). SS-31 refers to its classification in the Szeto-Schiller peptide series; elamipretide is the INN (international nonproprietary name) used in clinical trials; Bendavia was the brand name during early Stealth BioTherapeutics development.
SS-31 does not directly affect NAD+ synthesis. However, by improving mitochondrial membrane potential and electron transport chain efficiency, SS-31 can reduce the relative NAD+ demand (less NAD+ is consumed compensating for inefficient mitochondria). The two interventions are complementary: SS-31 improves the structural integrity of the mitochondrial machinery that NAD+ supports. Many longevity researchers combine SS-31 with NMN/NR supplementation.
Research community dosing typically starts at 1 mg subcutaneously daily and may increase to 2–3 mg/day based on response. Clinical trials have used up to 4 mg/kg IV in acute settings, but chronic research use employs much lower doses. Given the limited human chronic-use data outside clinical trials, conservative dosing is appropriate.
Both target mitochondrial ROS but through different mechanisms. MitoQ is a CoQ10 analogue that concentrates in mitochondria and scavenges superoxide directly. SS-31 protects cardiolipin structure to preserve ETC efficiency and reduce ROS generation at the source. They are complementary rather than equivalent — MitoQ is oral and more accessible; SS-31 requires injection but has better clinical evidence from trials. Some researchers use both.