SS-31 vs Epitalon: Two Ageing Tetrapeptides Compared
SS-31 and Epitalon are both four-amino-acid peptides studied in ageing, but they act in different parts of the cell: SS-31 binds cardiolipin in the inner mitochondrial membrane to support energy production, while Epitalon is studied for telomerase, telomere length and the pineal gland’s melatonin rhythm. SS-31 (elamipretide) also has something Epitalon does not: randomised human trials and an FDA accelerated approval for a rare mitochondrial disease. Here is how they compare and which research questions each one fits.
Findings
- SS-31 is D-Arg-dimethylTyr-Lys-Phe-NH2, a tetrapeptide that selectively binds cardiolipin and helps cytochrome c carry electrons, raising the efficiency of ATP synthesis in isolated mitochondria (2014).
- In aged mice, a single dose of SS-31 restored skeletal muscle mitochondrial energetics to young levels within an hour, and eight days raised whole-animal endurance (2013).
- Epitalon is the tetrapeptide Ala-Glu-Asp-Gly. It induced telomerase and lengthened telomeres in human fibroblasts (2003), a result a group at Brunel University London extended to normal epithelial cells in 2025.
- On 19 September 2025 the FDA granted elamipretide accelerated approval as the first treatment for Barth syndrome, a rare inherited mitochondrial disease.
What is SS-31?
SS-31 is a synthetic tetrapeptide, D-Arg-dimethylTyr-Lys-Phe-NH2, studied clinically as elamipretide. It binds cardiolipin, a lipid of the inner mitochondrial membrane that works closely with the electron transport chain. In liposome and mitochondria experiments it interacted only with membranes containing cardiolipin, blocked the peroxidase activity that cytochrome c takes on when bound to cardiolipin, restored cytochrome c’s electron-carrier role and increased state 3 respiration and the efficiency of ATP synthesis (Birk et al., Br J Pharmacol, 2014). Its regulatory history is set out in SS-31 (elamipretide): from research to FDA approval.
The ageing research
SS-31’s ageing work centres on muscle. Old mice given one dose had their age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation and cell energy state reversed one hour later, measured in living muscle by magnetic resonance and optical spectroscopy, with no effect in young muscle; eight days of treatment raised whole-animal endurance (Siegel et al., Aging Cell, 2013). In 26-month-old female mice, eight weeks of SS-31 reversed the age-related fall in maximum mitochondrial ATP production, restored the muscle’s redox balance, increased gastrocnemius mass and fatigue resistance and raised treadmill endurance, without increasing mitochondrial content (Campbell et al., Free Radic Biol Med, 2019).
The human trials
Barth syndrome is a rare, serious inherited disease of the mitochondria (FDA, 2025), and the TAZPOWER investigators tracked cardiolipin markers as part of the trial. TAZPOWER was a 28-week randomised, double-blind, placebo-controlled trial followed by a 168-week open-label extension. Of the 10 patients who entered the extension, 8 reached week 168; their 6-minute walk distance improved at every time point, by a cumulative 96.1 metres at week 168, fatigue scores stayed below baseline and heart volumes trended better (Thompson et al., Genet Med, 2024). The FDA’s accelerated approval, announced on 19 September 2025, covers patients weighing at least 30 kg and rests on improved knee-extensor strength, with a confirmatory trial required (FDA, 2025). In a 218-participant phase 3 trial in primary mitochondrial myopathy, the drug was well tolerated but did not meet its primary endpoints (Karaa et al., Neurology, 2023).
What is Epitalon?
Epitalon, also spelled Epithalon, is the tetrapeptide Ala-Glu-Asp-Gly (Khavinson et al., Molecules, 2020), a synthetic analogue of epithalamin, a peptide preparation from the pineal gland (Goncharova et al., Exp Gerontol, 2005). Its research covers two themes: telomeres and the pineal gland’s control of melatonin and other hormones. The literature is reviewed in Epitalon: what the research actually shows.
The telomere research
Added to human fetal fibroblasts that do not normally make telomerase, Epitalon induced the enzyme’s catalytic subunit, telomerase activity and telomere elongation (Khavinson et al., Bull Exp Biol Med, 2003). A group at Brunel University London reported dose-dependent telomere lengthening in normal human epithelial cells and fibroblasts, driven by higher hTERT expression and telomerase activity (Al-Dulaimi et al., Biogerontology, 2025).
The hormone and life-span research
In old rhesus monkeys, Epitalon raised night-time melatonin, lowered basal glucose and insulin and normalised the insulin response to glucose, with no effect in young animals (Goncharova et al., Exp Gerontol, 2005). In a lifelong study of 54 female mice per group, it cut bone-marrow chromosome aberrations by 17.1%, lengthened the life span of the last 10% of survivors by 13.3% and raised maximum life span by 12.3%, with no change in mean life span (Anisimov et al., Biogerontology, 2003).
How do SS-31 and Epitalon compare side by side?
| Question | SS-31 | Epitalon |
|---|---|---|
| What is it? | Mitochondria-targeted synthetic peptide | Synthetic analogue of a pineal peptide preparation |
| Size | 4 residues, including a D-amino acid and dimethyltyrosine | 4 amino acids (Ala-Glu-Asp-Gly) |
| Main research area | Mitochondrial disease, muscle ageing, energy production | Telomeres, melatonin rhythm, life span |
| Mechanism | Binds cardiolipin, supports electron transport and ATP synthesis | Telomerase induction, pineal and endocrine regulation |
| Human evidence | Randomised trials; FDA accelerated approval for Barth syndrome (2025) | Small studies of melatonin in elderly people |
| Forms we supply | 10 mg vial | 10 mg vial |
Which one fits which research question?
- Mitochondrial energy output, oxidative stress and muscle function: SS-31, whose studies measure ATP production, redox status and endurance directly.
- Telomere length and telomerase activity: Epitalon, which has the human cell telomere studies.
- Melatonin and daily hormone rhythm in older subjects: Epitalon.
- Translation to human disease endpoints: SS-31, which has controlled human trials and a regulatory approval behind it.
Can SS-31 and Epitalon be studied together?
No published study has tested them as a pair. Because they act in different compartments, the mitochondrial membrane for SS-31 and telomeres and pineal signalling for Epitalon, a design using both keeps two distinguishable variables, provided each has its own arm. SS-31 is compared with another mitochondrial peptide in MOTS-c vs SS-31, and sits alongside MOTS-c in the Mitochondrial Energy stack. For Epitalon set against a cofactor rather than a peptide, see Epitalon vs NAD+.
How are SS-31 and Epitalon supplied?
Both come as 10 mg lyophilised vials, reconstituted with bacteriostatic water: see the SS-31 reconstitution guide and the Epitalon reconstitution guide. Buying guides: SS-31 and Epitalon. Certificates of analysis are on the lab reports page, and every order ships from within Canada by Canada Post Xpresspost.
SS-31 and Epitalon are supplied for laboratory research use only. Elamipretide is an approved medicine in the United States for Barth syndrome; the SS-31 we supply is a research material, not that medicine.
Frequently asked questions
What is the difference between SS-31 and Epitalon?
Both are four-residue peptides studied in ageing. SS-31 binds cardiolipin in the inner mitochondrial membrane and supports ATP production. Epitalon is studied for telomerase, telomere length and the pineal melatonin rhythm.
Is SS-31 FDA approved?
Elamipretide, the clinical name for SS-31, received FDA accelerated approval on 19 September 2025 as the first treatment for Barth syndrome, for patients weighing at least 30 kg. Epitalon has no FDA approval.
Which has more human research, SS-31 or Epitalon?
SS-31. It has randomised, placebo-controlled trials in Barth syndrome and primary mitochondrial myopathy. Epitalon’s human data are small studies of melatonin in elderly people.
Can SS-31 and Epitalon be studied together?
No published study has tested them as a pair. Because they act in different parts of the cell, a design with separate arms can attribute each change to one peptide.
Where can I buy SS-31 and Epitalon in Canada?
Vistara Labs supplies both as 10 mg lyophilised vials, shipped from within Canada by Canada Post Xpresspost with certificates of analysis on the lab reports page.
Product details from vistaralabs.ca, October 2026. Sources: Birk AV et al. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br J Pharmacol. 2014. PMID 24134698. Siegel MP et al. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 2013. PMID 23692570. Campbell MD et al. Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med. 2019. PMID 30597195. Thompson WR et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024. PMID 38602181. US Food and Drug Administration. FDA grants accelerated approval to first treatment for Barth syndrome. 19 September 2025. fda.gov. Karaa A et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology. 2023. PMID 37268435. Khavinson V et al. AEDG peptide (Epitalon) stimulates gene expression and protein synthesis during neurogenesis: possible epigenetic mechanism. Molecules. 2020. PMID 32019204. Goncharova ND et al. Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas. Exp Gerontol. 2005. PMID 15664732. Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003. PMID 12937682. Al-Dulaimi S et al. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025. PMID 40908429. Anisimov VN et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology. 2003. PMID 14501183.
More on this: Cellular Energy & Mitochondrial Research.
All products supplied by Vistara Labs are intended for laboratory research use only. They are not drugs, are not approved for human or veterinary use, and are not intended to diagnose, treat, cure or prevent any condition. Nothing on this page constitutes medical advice or guidance for use in humans.
