Klotho KL-VS variant
DEKlotho-KL-VS-Variante
The KL-VS haplotype of the klotho gene is a set of six linked variants. Two of them change amino acids (F352V and C370S) in exon 2. It raises serum klotho protein. And it is tied to longevity, but only if you carry one copy, not two. That pattern is called 'heterozygote advantage'. One-copy (heterozygous) carriers show higher circulating klotho. In several studies, they also show better cognition and lower dementia risk. Brain MRI even found greater volume in the right dorsolateral prefrontal cortex in heterozygotes (Yokoyama et al., 2015). Later work linked serum klotho to prefrontal network strength (Yokoyama et al., 2017). (The Dubal et al. 2014 study reported cognition outcomes, not fMRI.) The variant also goes with better cardiovascular and bone-density profiles in some groups. Mechanistically, higher serum klotho is thought to boost FGF23 co-receptor signaling, tune the Wnt and IGF-1 pathways, and protect neurons, beyond its hormonal roles.
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Sources
- Yokoyama JS, Sturm VE, Bonham LW, et al. (2015). Variation in longevity gene KLOTHO is associated with greater cortical volumes. Annals of Clinical and Translational Neurologydoi:10.1002/acn3.161
- Liu H, Fergusson MM, Castilho RM, et al. (2007). Augmented Wnt signaling in a mammalian model of accelerated aging. Sciencedoi:10.1126/science.1143578
- Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L. (2014). Life extension factor klotho enhances cognition. Cell Reportsdoi:10.1016/j.celrep.2014.03.076