Klotho gene therapy

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, transgenic Klotho overexpression has extended lifespan (Kurosu et al., 2005), and AAV-mediated Klotho gene therapy has improved kidney function and rescued cognitive deficits in disease models. In aged rhesus macaques, peripheral injection of recombinant Klotho protein — not gene therapy — enhanced cognition (Castner et al., 2023); AAV-Klotho gene therapy in primates has not yet been published. 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.