Hormonal
Klotho protein functions as an anti-aging agent by inhibiting four major aging pathways (TGF-β, IGF-1, Wnt, NF-κB) and promoting antioxidant defenses, with deficiency leading to accelerated aging phenotypes and overexpression extending lifespan.
Maintaining healthy kidney function and managing metabolic health (blood sugar, blood pressure) may help preserve natural Klotho levels, which are linked to longevity. While direct Klotho supplementation is not yet a standard consumer intervention, lifestyle factors that support kidney health and reduce inflammation (like exercise and certain diets) are associated with higher Klotho expression.
Remarkably, Klotho inhibits four pathways that have been linked to aging in various ways: Transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), Wnt and NF-κB... Furthermore, Klotho increases cell-protective antioxidant enzymes through Nrf2 and FoxO. Overexpression of Klotho has opposite effects, extending lifespan.
Why this rating
Strong preclinical evidence in mice (knockout/overexpression) and consistent observational data in humans linking low levels to mortality, though direct human therapeutic trials are limited.
Source
Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations
Gérald J. Prud’homme et al. · Frontiers in Aging · 2022
DOI 10.3389/fragi.2022.931331
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