How does SS-31 actually get into mitochondria?

SS-31's structure is perfectly designed for mitochondrial targeting. The peptide is small (just 4 amino acids), water-soluble, and carries a net positive charge. Mitochondria maintain a strong negative membrane potential (~-180mV) across their inner membrane, which electrostatically attracts positively charged molecules. SS-31 accumulates in the inner mitochondrial membrane at concentrations 1000-5000x higher than in the cytoplasm. Once there, its dimethyltyrosine residue interacts with cardiolipin, a unique phospholipid found almost exclusively in the inner mitochondrial membrane. This isn't just about getting there—it's about going exactly where it needs to act. The mitochondrial electron transport chain complexes are embedded in the cardiolipin-rich inner membrane, so SS-31 positions itself precisely where oxidative damage originates.

What's the current status of clinical trials for Elamipretide?

Mixed results have slowed development but research continues. The EMBRACE trial for Barth syndrome (a rare mitochondrial disease affecting boys) showed improvements in a key walking test, leading to FDA breakthrough therapy designation. However, the larger TAZPOWER trial in Barth syndrome didn't meet its primary endpoint, though positive trends in secondary measures were observed. In heart failure (HFpEF), the RESTORE-HF trial showed no significant improvement in the primary endpoint of left ventricular end-systolic volume, disappointing expectations. Stealth BioTherapeutics, the developer, has continued trials in primary mitochondrial myopathy and dry AMD. The drug clearly has biological activity—biomarkers often improve—but translating that into clinical endpoints has proven challenging. As of 2024, Elamipretide remains investigational without FDA approval.

Can SS-31 slow aging?

That's the longevity research community's hope, supported by compelling preclinical data. In aged mice, SS-31 treatment improved skeletal muscle function, reduced oxidative stress markers, improved insulin sensitivity, and partially reversed age-related changes in mitochondrial function. The theory is sound: mitochondrial dysfunction is a hallmark of aging, ROS accumulation damages cells over time, and restoring mitochondrial efficiency could be fundamentally anti-aging. Human data is much more limited. The clinical trials have focused on disease states, not healthy aging. Whether chronic SS-31 use in healthy older adults would extend healthspan or lifespan remains completely untested in humans. Longevity enthusiasts using research peptides are essentially running their own experiments, with all the risks that implies.

How does SS-31 compare to other mitochondrial peptides like MOTS-c or Humanin?

They work through completely different mechanisms. SS-31 is a synthetic peptide that physically localizes to the inner mitochondrial membrane and stabilizes cardiolipin. It's like a molecular Band-Aid that reinforces the membrane. MOTS-c is a mitochondrial-derived peptide (encoded in mitochondrial DNA) that acts more like a signaling molecule—it goes to the nucleus, affects gene expression, and improves metabolic function systemically, particularly glucose metabolism. Humanin is another mitochondrial-derived peptide focused on cytoprotection and anti-apoptosis, with strong neuroprotective effects. There's no direct competition since they target different pathways. Theoretically, they could be complementary: SS-31 improves mitochondrial efficiency at the membrane level while MOTS-c and Humanin affect signaling and gene expression. No one has studied combinations in humans.

What are the side effects of SS-31/Elamipretide?

Clinical trials have reported a favorable safety profile. The most common side effect is injection site reactions—redness, pain, or swelling where the subcutaneous injection is given. These are typically mild and transient. Some participants reported headaches and dizziness. In longer trials, there were no consistent signals of serious adverse events related to the drug. Because SS-31 concentrates so specifically in mitochondria, it seems to have limited off-target effects. However, clinical trial populations have been relatively small and durations moderate. Long-term effects of chronic mitochondrial enhancement remain unknown. The theoretical concern—does improving cellular energy production have any downside over years?—can't be answered yet.

What's the typical research dosing for SS-31?

Clinical trials have used a range of doses depending on the indication. The EMBRACE trial used 40mg subcutaneously once daily. Other trials have tested 4mg to 40mg daily, with higher doses generally showing more effect on biomarkers. The peptide has a short plasma half-life (1-2 hours) but its mitochondrial concentration persists longer, so once-daily dosing appears sufficient. Research peptide users have reported various protocols, but without clinical guidance, optimal dosing for general 'mitochondrial support' is unknown. Animal studies used 1-5mg/kg, which would translate to quite high human doses. Starting conservatively and assessing response makes sense for researchers exploring this peptide.

Can SS-31 help with exercise performance?

It's biologically plausible but unproven in healthy athletes. Mitochondria are the powerhouses of cells—improved mitochondrial function should theoretically enhance aerobic capacity and endurance. In patients with mitochondrial myopathy, SS-31 has shown improvements in exercise tolerance as measured by the 6-minute walk test. However, these patients have dysfunctional mitochondria to begin with; it's unclear whether healthy, optimally-functioning mitochondria would benefit similarly. No studies have been conducted in athletes or healthy exercising individuals. The research peptide community has reported subjective improvements in energy and recovery, but placebo effects are strong for performance-related outcomes. Until controlled studies exist, any claims about athletic enhancement remain speculative.

Homechevron_rightPeptideschevron_rightSS-31 / Elamipretide

Mitochondrial

scheduleHalf-life: ~1-2 hours in plasma (but concentrates in mitochondria for prolonged effect)

SS-31 / Elamipretide

SS-31 (Elamipretide, Bendavia, MTP-131)

SS-31, now known as Elamipretide, represents a new frontier in medicine: drugs that target mitochondria directly. This small tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) has a unique ability to concentrate in the inner mitochondrial membrane, where it binds to cardiolipin—a phospholipid essential for electron transport chain function. When mitochondria are stressed (by ischemia, aging, disease), cardiolipin becomes oxidized and disorganized, leading to electron leak, reduced ATP production, and cell death. SS-31 stabilizes cardiolipin structure, improves electron transport efficiency, reduces reactive oxygen species (ROS) generation at the source, and protects against apoptosis. In preclinical studies, it's shown remarkable protective effects in models of heart attack, kidney injury, neurodegenerative disease, and aging. Human clinical trials have focused on primary mitochondrial myopathies (genetic diseases causing mitochondrial dysfunction) and heart failure with preserved ejection fraction. The concept is revolutionary: rather than trying to mop up oxidative damage after it occurs, SS-31 goes to where it's generated and prevents it.

What is SS-31 / Elamipretide?
Research Benefits
How SS-31 / Elamipretide Works
Research Applications

References

What is SS-31 / Elamipretide?

Research Benefits

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Protects mitochondria from oxidative damage

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Improves cellular ATP production

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Reduces mitochondrial ROS generation

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Stabilizes cardiolipin in inner mitochondrial membrane

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May improve exercise capacity in mitochondrial disease

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Protects tissues during ischemia-reperfusion

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Potential anti-aging effects at cellular level

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Crosses blood-brain barrier

Research Applications

science

Primary mitochondrial myopathies

Active research area with published studies

science

Heart failure with preserved ejection fraction (HFpEF)

Active research area with published studies

science

Ischemia-reperfusion injury

Active research area with published studies

science

Aging and cellular senescence

Active research area with published studies

science

Neurodegenerative diseases

Active research area with published studies

science

Kidney injury

Active research area with published studies

science

Dry age-related macular degeneration

Active research area with published studies

science

Barth syndrome

Active research area with published studies

Frequently Asked Questions

Scientific References

SS-31 Peptide Reverses the Mitochondrial Phenotype of Aging

Aging Cell (2018)

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Elamipretide in Patients with Barth Syndrome: A Randomized Trial

Circulation: Heart Failure (2021)

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Mitochondria-Targeted Therapeutics for Treatment of Ischemia-Reperfusion Injury

Antioxidants & Redox Signaling (2020)

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Quick Reference

Molecular Weight639.8 Da

Half-Life~1-2 hours in plasma (but concentrates in mitochondria for prolonged effect)

Purity≥98% for research applications

FormLyophilized powder | Subcutaneous injection in clinical trials

Sequence

D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2',6'-dimethyltyrosine)

Storage

Store lyophilized at -20°C | Reconstituted solution at 2-8°C | Protect from light

Related Peptides

Metabolic / Longevity

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Humanin

Longevity & Neuroprotection

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SS-31 (Elamipretide, Bendavia, MTP-131)

What is SS-31 / Elamipretide?

Research Benefits

check_circle

Protects mitochondria from oxidative damage

check_circle

Improves cellular ATP production

check_circle

Reduces mitochondrial ROS generation

check_circle

Stabilizes cardiolipin in inner mitochondrial membrane

check_circle

May improve exercise capacity in mitochondrial disease

check_circle

Protects tissues during ischemia-reperfusion

check_circle

Potential anti-aging effects at cellular level

check_circle

Crosses blood-brain barrier

Research Applications

science

Primary mitochondrial myopathies

Active research area with published studies

science

Heart failure with preserved ejection fraction (HFpEF)

Active research area with published studies

science

Ischemia-reperfusion injury

Active research area with published studies

science

Aging and cellular senescence

Active research area with published studies

science

Neurodegenerative diseases

Active research area with published studies

science

Kidney injury

Active research area with published studies

science

Dry age-related macular degeneration

Active research area with published studies

science

Barth syndrome

Active research area with published studies

Frequently Asked Questions

Scientific References

SS-31 Peptide Reverses the Mitochondrial Phenotype of Aging

Aging Cell (2018)

open_in_new

Elamipretide in Patients with Barth Syndrome: A Randomized Trial

Circulation: Heart Failure (2021)

open_in_new

Mitochondria-Targeted Therapeutics for Treatment of Ischemia-Reperfusion Injury

Antioxidants & Redox Signaling (2020)

open_in_new

SS-31 / Elamipretide

SS-31 (Elamipretide, Bendavia, MTP-131)

Table of Contents

What is SS-31 / Elamipretide?

Research Benefits

Research Applications

Primary mitochondrial myopathies

Heart failure with preserved ejection fraction (HFpEF)

Ischemia-reperfusion injury

Aging and cellular senescence

Neurodegenerative diseases

Kidney injury

Dry age-related macular degeneration

Barth syndrome

Frequently Asked Questions

How does SS-31 actually get into mitochondria?

What's the current status of clinical trials for Elamipretide?

Can SS-31 slow aging?

How does SS-31 compare to other mitochondrial peptides like MOTS-c or Humanin?

What are the side effects of SS-31/Elamipretide?

What's the typical research dosing for SS-31?

Can SS-31 help with exercise performance?

Scientific References

SS-31 Peptide Reverses the Mitochondrial Phenotype of Aging

Elamipretide in Patients with Barth Syndrome: A Randomized Trial

Mitochondria-Targeted Therapeutics for Treatment of Ischemia-Reperfusion Injury

Quick Reference

Related Peptides

SS-31 / Elamipretide

SS-31 (Elamipretide, Bendavia, MTP-131)

Table of Contents

What is SS-31 / Elamipretide?

Research Benefits

Research Applications

Primary mitochondrial myopathies

Heart failure with preserved ejection fraction (HFpEF)

Ischemia-reperfusion injury

Aging and cellular senescence

Neurodegenerative diseases

Kidney injury

Dry age-related macular degeneration

Barth syndrome

Frequently Asked Questions

How does SS-31 actually get into mitochondria?

What's the current status of clinical trials for Elamipretide?

Can SS-31 slow aging?

How does SS-31 compare to other mitochondrial peptides like MOTS-c or Humanin?

What are the side effects of SS-31/Elamipretide?

What's the typical research dosing for SS-31?

Can SS-31 help with exercise performance?

Scientific References

SS-31 Peptide Reverses the Mitochondrial Phenotype of Aging

Elamipretide in Patients with Barth Syndrome: A Randomized Trial

Mitochondria-Targeted Therapeutics for Treatment of Ischemia-Reperfusion Injury

Quick Reference

Related Peptides