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Therapeutics

Klotho gene therapy

DEKlotho-Gentherapie

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Klotho is a transmembrane protein and co-receptor for FGF23 that declines markedly with age; its soluble circulating form (s-Klotho) suppresses Wnt and TGF-β signalling and has been associated with renal function, cognitive health, and cardiovascular protection in observational studies. In mouse models, AAV-mediated Klotho overexpression has increased lifespan, improved kidney function, and reduced cognitive decline, and a single intramuscular injection of klotho-encoding AAV enhanced synaptic plasticity and cognition in aged non-human primates. Human longevity application remains strictly preclinical; BioViva and affiliated researchers have reported self-administered gene therapy experiments in single individuals outside regulated clinical frameworks, but these lack controlled safety or efficacy data and should not be interpreted as evidence of benefit. Risks include disruption of FGF23-phosphate homeostasis, possible ectopic calcification, and the general immunogenicity and off-target concerns of systemic AAV delivery.

Sources

  1. Kuro-o M, Matsumura Y, Aizawa H et al.. (1997). Mutation of the mouse klotho gene leads to a syndrome resembling ageing. *Nature*doi:10.1038/36285
  2. Castner SA, Macht VA, Dighe M et al.. (2023). Longevity factor klotho enhances cognition in aged nonhuman primates. *Nature Aging*doi:10.1038/s43587-023-00441-x