Humanin vs SS-31
A neutral, side-by-side comparison of two anti-aging & longevity peptides — their mechanisms, dosing ranges, administration routes, side effects, and research evidence. For research and educational purposes only.
Humanin
Humanin is a 21-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of the mitochondrial genome — discovered in 2001 through a screen for neuroprotective factors in Alzheimer's disease. It is the founding member of a new class of peptide hormones encoded by mitochondria, not nuclear DNA. Circulating humanin levels decline sharply with age and are inversely correlated with cardiovascular disease risk, insulin resistance, and cognitive decline.
Full profileSS-31
SS-31 (Elamipretide) is a mitochondria-targeted peptide that concentrates in the inner mitochondrial membrane, protecting cardiolipin and restoring mitochondrial function. It is being studied for heart failure, aging, and metabolic disease. One of the most exciting longevity-adjacent peptides in current research.
Full profile| Humanin | SS-31 | |
|---|---|---|
| Category | Anti-Aging & Longevity | Anti-Aging & Longevity |
| Also known as | HN, HNG (Gly14-Humanin — more potent analog), Mitochondrial-derived peptide | Elamipretide, MTP-131, Bendavia, Szeto-Schiller peptide 31 |
| Evidence | Research-stage | Investigational (in trials) |
| Dosing range | 100mcg–2mg mcg, Daily or 3–5x weekly | 1mg–10mg mg, daily or every other day |
| Administration | Subcutaneous injection, Intranasal (for CNS applications), Intravenous (clinical studies) | Subcutaneous injection, Intravenous (clinical trials) |
| Key side effects | Generally well-tolerated in animal studies, No significant adverse effects reported at research doses, Potential interaction with GH/IGF-1 axis (IGF-1 suppresses humanin production), Long-term human safety data limited | Injection site reactions, Nausea (rare), Generally well-tolerated in clinical trial populations |
| Cited sources | 3 references | 2 references |
Key differences
- Evidence level differs: Humanin is research-stage, while SS-31 is investigational (in trials).
- Administration: Humanin — Subcutaneous injection, Intranasal (for CNS applications), Intravenous (clinical studies); SS-31 — Subcutaneous injection, Intravenous (clinical trials).
- Dosing units differ: Humanin is dosed in mcg, SS-31 in mg — they operate at different scales.
- Frequency: Humanin is typically Daily or 3–5x weekly; SS-31 is daily or every other day.
- Research depth: this profile cites 3 sources for Humanin vs 2 for SS-31.
How each works
Humanin
Humanin acts through multiple receptors (CNTFR/WSX-1/gp130 trimeric complex and FPRL1) to exert neuroprotection, cardioprotection, and metabolic effects. Key findings: humanin inhibits neuronal apoptosis in Alzheimer's disease models by blocking IGFBP-3 death signaling, reduces cardiovascular disease markers in clinical studies, improves insulin sensitivity in diabetic models, and reduces oxidative stress. IGF-1 downregulates humanin production — individuals on GH/IGF-1 therapies may have suppressed endogenous humanin. Centenarians have elevated humanin levels compared to age-matched controls.
SS-31
SS-31 selectively accumulates in mitochondria and binds cardiolipin — a phospholipid critical for the electron transport chain. By stabilizing cardiolipin, SS-31 restores ATP production, reduces reactive oxygen species (ROS), and prevents mitochondrial permeability transition. Animal studies show dramatic reversal of mitochondrial dysfunction in aged tissues.
This comparison aggregates public research and structured profile data for informational purposes only. It is not medical advice and does not recommend either compound for human use. Consult a qualified healthcare provider before considering any peptide.