Klotho 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.
Klotho
Anti-aging protein discovered in 1997 whose deficiency causes a syndrome resembling accelerated aging across multiple organ systems. Circulating soluble klotho declines ~40% from age 40–80. Research into klotho-derived peptides and recombinant protein explores neuroprotection, cardiac protection, renal anti-fibrosis, and metabolic anti-aging benefits. The KL-VS polymorphism provides a natural human model of elevated klotho activity.
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| Klotho | SS-31 | |
|---|---|---|
| Category | Anti-Aging & Longevity | Anti-Aging & Longevity |
| Also known as | α-Klotho, soluble Klotho, KL-VS, klotho protein, KL1 domain | Elamipretide, MTP-131, Bendavia, Szeto-Schiller peptide 31 |
| Evidence | Research-stage | Investigational (in trials) |
| Dosing range | 1mcg/kg–10mcg/kg mcg/kg, every 3–7 days IV or SC (research) | 1mg–10mg mg, daily or every other day |
| Administration | Intravenous (research), Subcutaneous injection | Subcutaneous injection, Intravenous (clinical trials) |
| Key side effects | Hypophosphatemia (klotho inhibits FGF23 signaling → phosphate wasting), Hypocalcemia (secondary to phosphate effects), Altered vitamin D metabolism, Potential for altered mineral homeostasis with chronic administration | Injection site reactions, Nausea (rare), Generally well-tolerated in clinical trial populations |
| Cited sources | 2 references | 2 references |
Key differences
- Evidence level differs: Klotho is research-stage, while SS-31 is investigational (in trials).
- Administration: Klotho — Intravenous (research), Subcutaneous injection; SS-31 — Subcutaneous injection, Intravenous (clinical trials).
- Dosing units differ: Klotho is dosed in mcg/kg, SS-31 in mg — they operate at different scales.
- Frequency: Klotho is typically every 3–7 days IV or SC (research); SS-31 is daily or every other day.
How each works
Klotho
α-Klotho functions as both a transmembrane co-receptor for FGF23 (regulating phosphate and vitamin D) and as a shed soluble circulating factor with FGF23-independent longevity effects. Soluble klotho activates longevity-associated pathways: Nrf2/antioxidant defense, FOXO transcription factors, and Wnt/TGF-β inhibition for anti-fibrotic effects. The klotho-deficient mouse ages rapidly and dies young; klotho-overexpressing mice live 20–30% longer.
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.