Klotho — The Longevity Protein
Klotho is a transmembrane protein and circulating hormone named after the Greek Fate who spins the thread of life. Mice lacking klotho age rapidly and die young; mice overexpressing klotho live 20–30% longer. In humans, higher circulating klotho levels are associated with better cognitive function, lower cardiovascular risk, and reduced all-cause mortality. Klotho declines with age and is considered a key biomarker of biological aging.
Mechanism of Action
Klotho acts as a co-receptor for FGF23 (regulating phosphate and vitamin D metabolism) and as a circulating hormone that inhibits IGF-1 and Wnt signalling (anti-aging pathways). It reduces oxidative stress via Nrf2 activation, protects against kidney fibrosis, and promotes neuroplasticity. Soluble klotho (shed from the membrane) has systemic anti-aging effects.
Human Trial Evidence
No approved klotho supplement exists. Klotho is a research target, not a retail product. Strategies to increase klotho: exercise (most reliable — 30 min aerobic exercise increases klotho by ~15%), vitamin D supplementation, caloric restriction, and reducing phosphate intake. Several pharmaceutical klotho mimetics are in Phase I/II trials (2023–2025).
Dosing Protocol
Not available as a supplement. Lifestyle interventions to increase klotho: aerobic exercise (30–60 min/day), vitamin D3 (2,000–5,000 IU/day), low-phosphate diet (reduce processed foods), and caloric restriction. Monitor serum klotho levels as a longevity biomarker (reference range: 400–700 pg/mL).
Safety & Contraindications
N/A — no supplement form available. Klotho is a biomarker and research target. Pharmaceutical klotho therapies are in early clinical trials and not yet approved.