SS-31 (Elamipretide)

Human clinical Anti-Aging & Longevity In 1 protocol 3 sources

SS-31, also known as elamipretide, is a mitochondria-targeted peptide that binds to cardiolipin in the inner mitochondrial membrane. It helps restore mitochondrial function, reduce oxidative stress, and improve cellular energy production. Research has heavily focused on its potential for treating heart failure, mitochondrial myopathies, and age-related cellular decline.

01Dosing reference

Amount

2-4 mg/day

Frequency

Once daily via subcutaneous injection

Cycle

4-8 weeks on, followed by 4 weeks off

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

Mitochondrial Targeting and Binding

SS-31 selectively penetrates cells and concentrates in the inner mitochondrial membrane, where it binds to cardiolipin, a crucial structural lipid.

Membrane Stabilization

By stabilizing cardiolipin, it optimizes the structure of the electron transport chain complexes, improving electron transfer efficiency and reducing electron leak.

Restoration of Cellular Energy

This optimization leads to increased ATP (energy) production and a significant reduction in pathological reactive oxygen species (ROS), protecting the cell from oxidative damage.

03Human evidence

Improvements in exercise tolerance in some trials for primary mitochondrial myopathy (PMM).

Phase 2 trials showed increased 6-minute walk test distances, though a subsequent Phase 3 trial (SPIMM-301) did not meet its primary efficacy endpoints, highlighting the complexity of treating PMM.

Demonstrated safety and potential functional improvements in heart failure patients.

Clinical trials in patients with heart failure with reduced ejection fraction (HFrEF) showed the peptide was well-tolerated and suggested potential benefits in left ventricular volumes.

04Preclinical evidence

Protection against ischemia-reperfusion injury in multiple organs.

Animal models demonstrated that SS-31 preserves mitochondrial structure and reduces infarct size in the heart and protects against acute kidney injury following restricted blood flow.

Reversal of age-related decline in skeletal muscle function.

Studies in aged mice showed that SS-31 treatment improved mitochondrial quality, increased ATP production, and restored exercise capacity to levels seen in younger mice.

05What is known vs. unknown

Reasonably established

Selectively targets and concentrates in the inner mitochondrial membrane.
Binds specifically to cardiolipin to stabilize mitochondrial structure.
Reduces pathological oxidative stress without interfering with normal cellular signaling.
Has undergone extensive human clinical trials for rare mitochondrial diseases and heart failure.

Unknowns & limits

Long-term efficacy for broad anti-aging or systemic health optimization remains unproven in humans.
Mixed results in Phase 3 clinical trials for primary mitochondrial myopathy have complicated its regulatory approval path.
Optimal dosing protocols for general longevity and performance enhancement are still speculative.

06Safety & regulatory context

Regulatory statusSS-31 (Elamipretide) has generally been well-tolerated in clinical trials, with the most common adverse events being mild to moderate injection site reactions, such as erythema (redness) and pruritus (itching). It is not FDA-approved for any indication, though it has received Fast Track and Orphan Drug designations for rare conditions like Barth syndrome and primary mitochondrial myopathy. It remains an investigational compound and is not approved for general anti-aging or performance use.

07Compared with MOTS-c

SS-31 (Elamipretide) vs. MOTS-c

Key difference

SS-31 is a synthetic peptide that structurally stabilizes cardiolipin to improve mitochondrial electron transport, whereas MOTS-c is an endogenous mitochondrial-derived peptide that acts as a metabolic regulator, primarily targeting AMPK.

When researchers discuss each

SS-31 is typically discussed in the context of structural mitochondrial repair, ischemia-reperfusion injury, and specific mitochondrial diseases. MOTS-c is discussed regarding metabolic regulation, obesity, insulin sensitivity, and exercise mimetics.

08Appears in protocols

✨ Anti-Aging & Longevity Protocol

5 mg/dayDaily

09Glossary

Cardiolipin

A unique lipid found almost exclusively in the inner mitochondrial membrane, essential for the proper structure and function of the enzymes that produce cellular energy.

Reactive Oxygen Species (ROS)

Highly reactive molecules containing oxygen that can cause cellular damage (oxidative stress) when produced in excess, often due to mitochondrial dysfunction.

Ischemia-Reperfusion Injury

Tissue damage caused when blood supply returns to tissue after a period of lack of oxygen, often leading to severe oxidative stress and mitochondrial damage.

10Knowledge check

Q1What is the primary molecular target of SS-31 within the cell?

Q2How does SS-31 affect reactive oxygen species (ROS) production?

Q3How should researchers most reasonably interpret the clinical trial results for SS-31 in primary mitochondrial myopathy (PMM)?

Q4Which description best matches how researchers typically discuss SS-31 compared with MOTS-c?

Q5Which statement most accurately reflects SS-31’s safety and regulatory status as described in the dossier?

11Sources

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Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.