Peptides
Evidence: Emerging (Phase 2/3 trials)
SS-31 (D-Arg-Dmt-Lys-Phe-NH2, also known as elamipretide/Bendavia) is a cell-permeable tetrapeptide that localizes to the inner mitochondrial membrane and binds cardiolipin via electrostatic interactions. This stabilizes cardiolipin against oxidative damage, preserving cristae integrity, reducing ROS production, and maintaining mitochondrial ATP production. SS-31 interacts with proteins in two functional groups: oxidative phosphorylation complexes and 2-oxoglutarate metabolic enzymes — all known cardiolipin binders. It restores mitochondrial function without acting as a direct antioxidant.
Standard: Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.
Maintenance: Research indicates dosing varies by indication. 4 mg daily SC in heart failure trials.
Administration: subcutaneousintravenous
Timing: Morning dosing preferred. No food timing restrictions.
Duration: Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.
SS-31 is the most clinically advanced mitochondrial-targeted peptide, with multiple Phase II/III trials. It received FDA Orphan Drug and Fast Track designations for Barth syndrome. In aged mice, 8 weeks of SS-31 reversed cardiac dysfunction to levels comparable to young hearts — a remarkable finding. The mechanism is unique: rather than scavenging ROS directly, it stabilizes the cardiolipin platform needed for efficient oxidative phosphorylation, reducing ROS at the source. This is arguably the most scientifically validated longevity peptide in development.
Research-grade or pharmaceutical-grade. Elamipretide is in clinical trials (Phase II/III) for Barth syndrome, heart failure, and primary mitochondrial myopathy. Not yet FDA-approved.
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