---
title: "SS-31 (Elamipretide)"
slug: "ss-31"
type: "compound"
category: "Longevity"
url: "https://peptidesciencethailand.com/compounds/ss-31"
description: "SS-31 targets damaged mitochondria to restore cellular energy. Cardiology trials, aging research, and mechanism explained. Independent evidence profile."
---
# SS-31 (Elamipretide)

*Mitochondria-Targeted Peptide, Cardiolipin Stabilization for Electron Transport Optimization*

**Category:** Longevity  
**Format:** Auto-Injector Pen  
**Amount:** 50mg  
**Purity:** >99.0% (HPLC)

## Overview

SS-31, also known as elamipretide (formerly Bendavia and MTP-131), is a synthetic mitochondria-targeted tetrapeptide with the sequence D-Arg-dimethylTyr-Lys-Phe-NH2. Developed from the Szeto-Schiller (SS) peptide series at Weill Cornell Medical College, SS-31 was designed with an alternating aromatic-cationic motif that enables it to concentrate in the inner mitochondrial membrane at concentrations approximately 1000- to 5000-fold greater than surrounding cytoplasm, driven by the mitochondrial membrane potential. This remarkable selectivity for the mitochondrial compartment distinguishes SS-31 from other antioxidant and cytoprotective compounds that operate at the cellular or systemic level.

The primary molecular target of SS-31 is cardiolipin, a unique phospholipid found almost exclusively in the inner mitochondrial membrane. Cardiolipin contains four fatty acid chains arranged in a distinctive dimeric phospholipid structure, and it plays essential roles in organizing the spatial arrangement of electron transport chain complexes, facilitating the formation of respiratory supercomplexes (complexes I, III, and IV assembled into higher-order structures), and maintaining the curvature of mitochondrial cristae, the membrane folds that massively increase the surface area available for oxidative phosphorylation.

SS-31 binds to cardiolipin through electrostatic and hydrophobic interactions, stabilizing its structure within the inner membrane. This stabilization has multiple downstream consequences. First, it preserves the organization of electron transport chain supercomplexes, ensuring efficient electron transfer from NADH through Complex I, to ubiquinone, through Complex III, to cytochrome c, and through Complex IV to molecular oxygen. When cardiolipin is oxidized or disorganized, as occurs with aging and in disease states, electron transfer becomes less efficient and electron leak increases, generating superoxide radicals that further damage cardiolipin in a self-amplifying cycle of mitochondrial dysfunction.

By stabilizing cardiolipin, SS-31 reduces electron leak from Complexes I and III, decreasing mitochondrial reactive oxygen species (ROS) production at the source rather than attempting to scavenge ROS after they have been generated. This mechanistic distinction is important: conventional antioxidants act as ROS scavengers downstream of production, while SS-31 prevents excessive ROS generation by optimizing electron transport efficiency. Research has demonstrated that SS-31 reduces mitochondrial ROS production by 30-50% in aged tissues without impairing the physiological ROS signaling required for normal cellular function.

SS-31 also interacts with cytochrome c, a heme protein that functions as an electron carrier between Complexes III and IV and that plays a critical dual role as a trigger of intrinsic apoptosis when released from the mitochondrial intermembrane space. Research has shown that SS-31 inhibits the peroxidase activity of the cardiolipin-cytochrome c complex, which under stress conditions catalyzes the oxidation of cardiolipin and promotes mitochondrial membrane permeabilization. By preventing this peroxidase activity, SS-31 preserves mitochondrial membrane integrity and reduces the pro-apoptotic signaling that contributes to cell death in ischemic and degenerative conditions.

Preclinical research has demonstrated SS-31's efficacy across multiple organ systems. In cardiac models, SS-31 reduces infarct size in ischemia-reperfusion injury by 50-60%, improves left ventricular function, and attenuates cardiac remodeling. In renal models, it protects against acute kidney injury and slows the progression of established kidney disease. Skeletal muscle studies in aged animals demonstrate improved exercise capacity, enhanced mitochondrial ATP production, and reduced oxidative damage with SS-31 administration.

Clinical development has progressed through multiple Phase 2 and Phase 3 trials. The TAZPOWER trial in Barth syndrome (a genetic cardiolipin deficiency disorder) demonstrated improved cardiac stroke volume and 6-minute walk distance. Trials in heart failure with reduced ejection fraction (HFrEF) showed acute improvements in left ventricular end-systolic volume. Ongoing research investigates SS-31 in age-related mitochondrial dysfunction, primary mitochondrial myopathy, and dry age-related macular degeneration.

The aging research applications of SS-31 are particularly strong. Studies in aged mice demonstrated that 8 weeks of SS-31 treatment reversed age-related mitochondrial dysfunction in skeletal muscle, restoring ATP production, improving redox homeostasis, and increasing exercise tolerance to levels approaching those of young animals. These effects were associated with restoration of mitochondrial proteome composition and normalization of the mitochondrial unfolded protein response.

The auto-injector pen format delivers 50mg of SS-31 in a pre-mixed solution for subcutaneous administration, enabling convenient dosing without intravenous infusion requirements.

## Mechanism of Action

### Step 1: Mitochondrial Membrane Concentration

SS-31's alternating aromatic-cationic structure drives selective accumulation in the inner mitochondrial membrane at 1000-5000x cytoplasmic concentrations, directed by the mitochondrial membrane potential. This targeting delivers the peptide directly to its site of action.

### Step 2: Cardiolipin Binding & Stabilization

SS-31 binds to cardiolipin through electrostatic and hydrophobic interactions, stabilizing this critical phospholipid within the inner membrane. Stabilized cardiolipin maintains the organization of electron transport chain supercomplexes and preserves cristae architecture.

### Step 3: Electron Transport Chain Optimization

Preserved supercomplex organization ensures efficient electron transfer through Complexes I, III, and IV, reducing electron leak and associated superoxide production. ATP synthesis efficiency improves as the proton gradient is maintained without excessive ROS-generating electron escape.

### Step 4: ROS Production Reduction at Source

By preventing electron leak at Complexes I and III, SS-31 reduces mitochondrial ROS generation by 30-50% without eliminating the physiological ROS signaling required for normal cellular function. This source-level reduction breaks the self-amplifying cycle of cardiolipin oxidation and mitochondrial damage.

### Step 5: Mitochondrial Membrane Integrity Preservation

SS-31 inhibits the peroxidase activity of the cardiolipin-cytochrome c complex, preventing stress-induced cardiolipin oxidation and mitochondrial membrane permeabilization. This preserves mitochondrial integrity and reduces pro-apoptotic signaling under cellular stress conditions.

## Researched Benefits

### Mitochondrial Function Restoration

Preclinical aging research demonstrates that SS-31 restores mitochondrial ATP production in aged tissues toward youthful levels. In aged skeletal muscle studies, 8 weeks of treatment normalized mitochondrial proteome composition, improved oxidative phosphorylation efficiency, and restored exercise capacity, representing a reversal of age-related mitochondrial decline.

### Oxidative Stress Reduction at Source

Unlike conventional antioxidants that scavenge ROS after production, SS-31 prevents excessive ROS generation by optimizing electron transport chain efficiency. This source-level approach reduces mitochondrial oxidative damage while preserving the physiological ROS signaling required for cellular homeostasis, stress adaptation, and immune function.

### Cardioprotective Properties

Research across multiple cardiac models demonstrates significant cardioprotective effects including 50-60% reduction in ischemia-reperfusion infarct size, improved left ventricular function, and attenuated cardiac remodeling. Clinical trials in heart failure have shown acute improvements in cardiac volumes, supporting translation of preclinical cardiovascular findings.

### Multi-Organ Cytoprotection

Because mitochondrial dysfunction is a common pathogenic mechanism across organ systems, SS-31's mitochondria-targeted mechanism provides protective effects in cardiac, renal, skeletal muscle, neural, and retinal tissues. This multi-organ applicability reflects the universal importance of mitochondrial health in cellular function and disease resistance.

## Dosage & Administration

| Parameter | Detail |
| --- | --- |
| Protocol | 0.25mg/kg per day administered subcutaneously, with dose adjustments based on specialist assessment and treatment goals |
| Route | Subcutaneous injection via auto-injector pen |
| Duration | Variable based on indication and specialist assessment. Research protocols have studied durations from single dose to 8 weeks of daily administration. |
| Cycle Notes | Optimal dosing frequency and cycle length for longevity applications are areas of active investigation. Research in aging models used daily administration for 8 weeks with sustained benefits observed. Clinical trial protocols have varied from single-dose acute settings to multi-week daily administration. |
| Reconstitution | No reconstitution required. The auto-injector pen contains pre-mixed SS-31 solution for subcutaneous administration. Store in refrigerator at 2-8 degrees C. Protect from light. |

> **Specialist note:** SS-31 is an investigational compound. Pre-treatment assessment should include baseline cardiac function evaluation, renal function panel, and assessment of current medications. Individuals with mitochondrial disorders should be evaluated by specialists. Dose calculation is weight-based and must be determined by a specialist.

## Compound Reference Data

| Property | Value |
| --- | --- |
| Format | Pre-filled Auto-Injector Pen |
| Amount | 50mg per pen |
| Purity | >99.0% |
| Purity Method | HPLC (High-Performance Liquid Chromatography) |
| Sequence | D-Arg-dimethylTyr-Lys-Phe-NH2 |
| Molecular Weight | 640.77 g/mol |
| Storage | Store refrigerated at 2-8 degrees C. Protect from light. Do not freeze. |
| Appearance | Clear, colorless solution in pre-filled pen |

## Medical Guidance

SS-31 (elamipretide) is an investigational compound that directly targets mitochondrial function. While its mechanism is focused on the inner mitochondrial membrane, effects on cellular energy metabolism, ROS production, and apoptotic signaling have systemic implications. Pre-treatment evaluation should include cardiac function assessment, renal function panel, and review of medications that affect mitochondrial function (including certain antibiotics, statins, and antidiabetic agents). Individuals with known mitochondrial disorders should be evaluated by a specialist familiar with the compound.

## Frequently Asked Questions

### What is SS-31 and how does it target mitochondria?

SS-31 (elamipretide) is a synthetic tetrapeptide with an alternating aromatic-cationic amino acid structure (D-Arg-dimethylTyr-Lys-Phe-NH2) that causes it to selectively concentrate in the inner mitochondrial membrane at 1000-5000 times cytoplasmic concentrations. There, it binds to and stabilizes cardiolipin, a phospholipid critical for organizing electron transport chain complexes and maintaining mitochondrial membrane integrity.

### How does SS-31 differ from conventional antioxidants?

Conventional antioxidants (vitamin C, vitamin E, NAC) work by scavenging reactive oxygen species after they have been generated. SS-31 takes a fundamentally different approach by preventing excessive ROS production at the source. By stabilizing cardiolipin and optimizing electron transport chain efficiency, SS-31 reduces electron leak from Complexes I and III, decreasing mitochondrial ROS generation by 30-50% while preserving the physiological ROS signaling needed for normal cellular function.

### What has SS-31 demonstrated in aging research?

In aged mice, 8 weeks of daily SS-31 administration reversed age-related mitochondrial dysfunction in skeletal muscle, restoring ATP production, normalizing mitochondrial proteome composition, improving redox balance, and increasing exercise capacity toward levels seen in young animals. These findings suggest that age-related mitochondrial decline may be partially reversible through targeted cardiolipin stabilization.

### Does SS-31 require specialist supervision?

Yes. SS-31 is an investigational compound with mechanisms directly affecting mitochondrial function and cellular energy metabolism. specialist evaluation is required to assess baseline organ function, identify potential interactions with medications affecting mitochondrial function, determine appropriate weight-based dosing, and monitor response. Individuals with diagnosed mitochondrial disorders should be evaluated by specialists.

### What clinical trials have studied SS-31?

SS-31 has been studied in Phase 2 and Phase 3 clinical trials across multiple indications. The TAZPOWER trial in Barth syndrome demonstrated improved cardiac stroke volume and exercise capacity. Trials in heart failure with reduced ejection fraction showed acute improvements in left ventricular volumes. Additional trials have investigated SS-31 in primary mitochondrial myopathy and dry age-related macular degeneration. Research in age-related mitochondrial dysfunction continues.

## Related Compounds

- /compounds/nad-plus
- /compounds/epithalon
- /compounds/mots-c