Peptide Reference Sheet

SS-31

SZETO-SCHILLER PEPTIDE 31  |  MITOCHONDRIA-TARGETED ANTIOXIDANT
01 — Identity

Name & Classification

SS-31 stands for Szeto-Schiller Peptide 31, named after its inventors Hazel Szeto and Peter Schiller. Its chemical name is D-Arg-2′6′-Dmt-Lys-Phe-NH₂, also known commercially as Elamipretide (MTP-131).

It is a synthetic tetrapeptide (4 amino acids) that selectively concentrates in the inner mitochondrial membrane where it binds cardiolipin — a phospholipid critical for electron transport chain function. It is classified as a mitochondria-targeted antioxidant and cardioprotective peptide.

02 — Origin

When It Was Developed

Early 2000s
Developed by Dr. Hazel Szeto at Weill Cornell Medical College. Originally designed as an opioid receptor agonist; the mitochondrial targeting was discovered serendipitously.
2004–2006
Landmark papers published showing SS-31 selectively concentrates in the inner mitochondrial membrane (IMM) and protects cardiolipin from oxidation — a completely novel mechanism.
2010s
Licensed to Stealth BioTherapeutics as Elamipretide (MTP-131). Phase 2/3 trials launched for heart failure with preserved ejection fraction (HFpEF), Barth syndrome, and primary mitochondrial myopathy.
2019–2022
Phase 3 MMPOWER-3 trial for Barth syndrome — a rare mitochondrial disease — showed functional improvement but missed primary endpoint. Research continued in cardiac, renal, and aging contexts.
2022–Present
Growing use in longevity and sports medicine. Animal studies show dramatic reversal of age-related mitochondrial dysfunction. No FDA approval; research peptide status in wellness space.
03 — Research History

Research Background

SS-31's defining mechanism is its ability to bind cardiolipin — a phospholipid unique to the inner mitochondrial membrane that is essential for organizing the electron transport chain (ETC) supercomplexes. With age and disease, cardiolipin becomes oxidized and fragmented, causing ETC inefficiency, increased ROS production, and mitochondrial collapse. SS-31 intercepts this process directly at the source.

A landmark 2021 study in Nature Aging showed that SS-31 in aged mice reversed multiple hallmarks of cardiac aging in weeks — not months — restoring mitochondrial cristae architecture, reducing oxidative stress, and improving cardiac output. This is one of the most dramatic aging reversal results seen with any single compound in animal models.

SS-31 also improves ATP production efficiency, reduces mitochondrial reactive oxygen species (ROS) without scavenging them, and preserves cytochrome c in the ETC rather than allowing its release as an apoptosis trigger.

04 — Key Benefits

Proposed Benefits

Binds and protects cardiolipin in the inner mitochondrial membrane
Restores ETC supercomplex organization and ATP synthesis efficiency
Reduces mitochondrial ROS without interfering with signaling ROS
Dramatic cardiac protection — reduces ischemia-reperfusion injury
Reverses age-related mitochondrial dysfunction in animal models
Improves exercise tolerance and physical capacity in aging
Renal protection — reduces acute kidney injury and fibrosis
Neuroprotective — improves neuronal mitochondrial function
05 — Reconstitution

10 mg Vial + 300 Units BAC Water

33.3 mcg
per unit drawn on insulin syringe
10,000
mcg total
0.3 mL
total volume
4–6 wk
shelf life (fridge)
300 units = 0.3 mL on a U-100 insulin syringe. Store refrigerated at 2–8°C after reconstitution. SS-31 is stable in solution but sensitive to repeated freeze-thaw cycles — do not freeze once reconstituted. Light-sensitive; store in original vial or amber container.
06 — Dosage

Dosage Reference

DoseUnits to DrawContext
1 mg/kg (clinical trials)IV / CLINICAL
5 mg (0.05–0.1 mg/kg)~1.5 uLOW / INTRO
10 mg~3 uCOMMON
20–30 mg6–9 uSTANDARD
50 mg15 uHIGH
Clinical trials used IV infusion at 0.05–0.25 mg/kg. Subcutaneous dosing in the wellness space commonly ranges from 10–30 mg/day. SS-31 has an extremely short half-life (~30 min plasma) but mitochondrial retention is prolonged. Injection site reactions (redness, mild pain) are the most commonly reported side effect.
07 — Monitoring

Biomarkers, Lab Tests & Ranges

SS-31 primarily acts on cardiac, mitochondrial, and renal systems. Monitor the following before starting, at 6 weeks, and at cycle end.

▸ Mitochondrial Function
BiomarkerLab TestClinical RangeOptimal Range
Lactate (resting)Serum LactateCLINICAL0.5–2.2 mmol/LOPTIMAL0.5–1.0 mmol/L
CoQ10 (Ubiquinol)Plasma CoQ10CLINICAL0.4–1.9 µg/mLOPTIMAL1.5–3.5 µg/mL
GDF-15
Mitochondrial stress signal
Serum GDF-15CLINICAL<1200 pg/mLOPTIMAL<400 pg/mL
8-OHdG
Oxidative DNA damage
Urine 8-OHdGCLINICAL<15 ng/mg creatinineOPTIMAL<5 ng/mg creatinine
▸ Cardiac Health
BiomarkerLab TestClinical RangeOptimal Range
NT-proBNP
Heart stress marker
Serum NT-proBNPCLINICAL<125 pg/mL (<75 yrs)OPTIMAL<50 pg/mL
Troponin I / THigh-sensitivity TroponinCLINICAL<0.04 ng/mL (standard)OPTIMALUndetectable / baseline stable
hsCRPHigh-sensitivity CRPCLINICAL<3.0 mg/LOPTIMAL<0.5 mg/L
▸ Renal & Metabolic Safety
BiomarkerLab TestClinical RangeOptimal Range
Creatinine / eGFRCMPCLINICALCreat 0.7–1.3 mg/dL / eGFR >60OPTIMALCreat 0.8–1.1 / eGFR >90
Cystatin C
Sensitive kidney marker
Serum Cystatin CCLINICAL0.5–1.0 mg/LOPTIMAL<0.7 mg/L
AST / ALTCMPCLINICALAST 10–40 / ALT 7–56 U/LOPTIMALAST <26 / ALT <26 U/L
CBCComplete Blood CountCLINICALStandard lab rangesOPTIMALMid-range; WBC 4.5–6.0
⚠ Optimal ranges reflect functional/longevity medicine targets. SS-31 is not FDA-approved. Cardiac biomarkers should be interpreted with a cardiologist if any abnormalities are present at baseline.
08 — Cycle Protocol

Cycle Length, Frequency & Timing

▸ How Long to Cycle
CLINICAL TRIAL
4–12 Weeks
Phase 2/3 trials used 4–12 week dosing windows; some chronic dosing studies extended to 6 months in mitochondrial myopathy.
PRACTITIONER CONSENSUS
8–12 Weeks
Most practitioners run 8–12 week cycles with a 4–8 week break. Some longevity protocols use continuous low-dose cycling given the strong safety profile.
SS-31 has shown no tolerance or desensitization in research literature. Its mitochondrial accumulation is rapid (within minutes) and sustained. Given its short plasma half-life, consistent daily dosing is more important than with longer-acting peptides.
▸ Frequency & Timing
VariableRecommendationWhy
FrequencyDaily (7×/week)SS-31 has a very short plasma half-life (~30 min). Daily dosing maintains mitochondrial cardiolipin protection continuously. Clinical trials all used daily dosing.
Fasted vs Fed~ Either acceptableSS-31's mechanism is not insulin-dependent. It goes directly to mitochondria regardless of metabolic state. Fasted AM is conventional but no strong preference in the data.
Morning (AM)✓ PreferredMorning dosing aligns with circadian mitochondrial activity peaks and ensures cardioprotection is active during the metabolically active daytime period.
Pre-exercise✓ Strongly consideredDosing 20–30 min before training maximizes mitochondrial protection during the oxidative stress of exercise — directly aligning with SS-31's core mechanism.
Wait to eat~ Not criticalNo evidence that food intake affects absorption or efficacy. Eat normally after injection.
PROTOCOL SUMMARY
8–12 wk
CYCLE LENGTH
Daily
FREQUENCY
AM
TIMING
Either
FED STATE
4–8 wk
BREAK