SS-31

SS-31, known pharmaceutically as Elamipretide, is a mitochondrial-targeting peptide designed to restore and protect mitochondrial function. This innovative four-amino-acid peptide (D-Arg-2'-6'-dimethyltyrosine-Lys-Phe-NH2) crosses the blood-brain barrier and specifically targets the inner mitochondrial membrane, where it binds to cardiolipin—a critical phospholipid essential for optimal mitochondrial energy production.

Mitochondria are the powerhouses of cells, responsible for generating ATP (cellular energy). Age-related mitochondrial dysfunction contributes to many diseases including cardiovascular disease, metabolic disorders, neurological diseases, and the general decline associated with aging. SS-31 works by restoring cardiolipin function, which is central to mitochondrial electron transport chain efficiency and cellular energy production. The peptide has emerged from decades of research into mitochondrial dysfunction and aging.

SS-31 has been extensively studied in clinical trials for heart failure, Barth syndrome, and other conditions associated with mitochondrial dysfunction. The peptide offers a novel approach to combating age-related decline by targeting the cellular energy production systems that underlie aging processes. Users report improved energy levels, enhanced physical performance, and better metabolic health.

SS-31's mechanism centers on restoration of cardiolipin, a unique phospholipid found almost exclusively in the inner mitochondrial membrane. Cardiolipin is essential for optimal function of the electron transport chain—the molecular machinery that generates ATP from the breakdown of nutrients. With aging, cardiolipin becomes oxidized and dysfunctional, impairing electron transport chain efficiency and dramatically reducing cellular energy production.

SS-31 crosses cell membranes and penetrates into mitochondria where it binds cardiolipin with high specificity. This binding prevents cardiolipin oxidation and restores its normal interactions with critical electron transport chain proteins. The result is restoration of electron transport efficiency, reduced reactive oxygen species (ROS) production, and dramatically improved ATP synthesis. This single mechanism addresses a fundamental cause of age-related cellular dysfunction.

By restoring cardiolipin function and mitochondrial energy production, SS-31 provides wide-ranging benefits across multiple tissues and organs. Tissues most dependent on mitochondrial function—including heart muscle, brain, and metabolically active tissues—show the greatest benefit from SS-31. The peptide's ability to reduce oxidative stress while simultaneously improving energy production makes it uniquely valuable for anti-aging applications.

Restoring Cellular Energy: SS-31 dramatically improves ATP production through restoration of electron transport chain efficiency. This increased cellular energy availability translates to improved physical performance, enhanced cognitive function, better metabolic health, and overall vigor. Users report feeling more energized and less fatigued throughout the day.

Reducing Oxidative Stress: Age-related mitochondrial dysfunction produces excessive reactive oxygen species (ROS) that damage cellular components. By restoring efficient electron transport, SS-31 reduces ROS production while simultaneously improving cellular antioxidant defenses through enhanced energy availability. This dual action provides superior mitochondrial protection compared to simple antioxidant supplementation.

Cardiovascular Health: The heart is perhaps the most energy-dependent organ, and mitochondrial dysfunction is central to heart disease pathology. SS-31 shows particular promise for cardiovascular health through restoration of cardiac mitochondrial function, improved cardiac energy metabolism, and protection against heart failure progression. The peptide has demonstrated benefits in clinical trials for various forms of heart disease.

Metabolic Optimization: Metabolic tissues including brown adipose tissue and muscle depend heavily on mitochondrial efficiency. SS-31 improves metabolic rate, enhances glucose metabolism, supports healthy weight management, and may improve insulin sensitivity through restoration of mitochondrial function in metabolic tissues.

SS-31 (Elamipretide) has been extensively studied in clinical trials and shows particularly strong evidence for Barth syndrome treatment, a rare genetic mitochondrial disorder. Clinical trials demonstrate that SS-31 administration improves cardiac function, reduces hospitalizations, and improves quality of life in Barth syndrome patients. The peptide has also been studied for acute heart failure, showing promise for improving cardiac function and reducing adverse outcomes.

Research in animal models of aging demonstrates that SS-31 reverses age-related mitochondrial dysfunction, improves physical performance, enhances cognitive function, and extends healthspan (healthy lifespan). Studies show restoration of cardiolipin function, improved mitochondrial bioenergetics, reduced oxidative stress, and improved tissue function across multiple organ systems. The research confirms SS-31's ability to address fundamental aging processes at the cellular level.

Cardiovascular research shows SS-31's protective effects against ischemia-reperfusion injury, heart failure progression, and age-related cardiac dysfunction. Metabolic studies demonstrate improved glucose homeostasis and metabolic health markers. Neurological research suggests potential benefits for neurodegenerative diseases associated with mitochondrial dysfunction.

Standard Dosing: For research and therapeutic use, SS-31 (Elamipretide) typical dosing ranges from 0.05-0.1 mg per injection administered via subcutaneous or intravenous route. Clinical trials typically employ IV administration at 0.05-0.1 mg doses. Lower doses are often used initially to assess individual response, with dose titration based on tolerance and effects.

Administration Methods: SS-31 can be administered subcutaneously or intravenously. IV administration provides rapid systemic distribution and is preferred in clinical settings. Subcutaneous administration offers convenience for self-administration and is commonly used in research protocols. The peptide is supplied as lyophilized powder requiring reconstitution with saline or bacteriostatic water.

Treatment Protocols: For mitochondrial support and anti-aging applications, dosing is typically 0.05-0.1 mg 2-3 times weekly via subcutaneous injection. Treatment courses range from 8-12 weeks with assessment of effects. Some advanced protocols use IV administration once or twice monthly combined with weekly subcutaneous injections for enhanced mitochondrial restoration.

Optimization Strategies: SS-31 effects are enhanced through combined use of antioxidants (CoQ10, NAD+ precursors), mitochondrial support nutrients (carnitine, succinate), regular exercise, and caloric restriction. These complementary approaches provide synergistic support for mitochondrial health and optimal benefits from SS-31.

Barth syndrome is a rare X-linked genetic disorder characterized by defective cardiolipin remodeling, leading to severe mitochondrial dysfunction, cardiomyopathy, and immunodeficiency. SS-31 shows remarkable promise for treating Barth syndrome by directly addressing the underlying cardiolipin dysfunction. Clinical trials demonstrate that Elamipretide administration improves cardiac function, reduces hospitalizations, and improves physical exercise capacity in Barth syndrome patients.

The success of SS-31 in Barth syndrome—a condition caused specifically by cardiolipin dysfunction—provides strong evidence for the peptide's mechanism and potential benefits for age-related cardiolipin deterioration. As cardiolipin becomes increasingly dysfunctional with aging, SS-31's ability to restore cardiolipin function suggests it may reverse fundamental aspects of aging pathology, particularly in energy-dependent tissues like the heart and brain.