Klotho was discovered in 1997 when a disrupted gene caused mice to develop every hallmark of premature ageing within weeks — osteoporosis, arteriosclerosis, muscle wasting, cognitive decline — and die at a fraction of their expected lifespan. The inverse experiment extended lifespan by twenty to thirty percent. The protein was named after Clotho, the Greek Fate who spins the thread of life. It remains one of the most studied proteins in longevity biology nearly three decades later.

In this episode, Dr. Ethan Hausman-Marquis examines Klotho from the ground up: the critical distinction between transmembrane α-Klotho and its circulating shed form sKlotho; how the FGF23 co-receptor mechanism explains the accelerated ageing phenotype of Klotho deficiency; what five separate longevity-associated pathways — including IGF-1/PI3K suppression, Wnt/β- ...