TitleSystemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging.
Publication TypeJournal Article
Year of Publication2017
AuthorsYokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal DB
JournalBrain Imaging Behav
Date Published2017 04
KeywordsAged, Aging, Biomarkers, Connectome, Female, Genetic Markers, Glucuronidase, Humans, Male, Nerve Net, Polymorphism, Single Nucleotide, Reproducibility of Results, Sensitivity and Specificity, Temporal Lobe, Tissue Distribution

Cognitive decline is a major biomedical challenge as the global population ages. Elevated levels of the longevity factor klotho suppress aging, enhance cognition, and promote synaptic plasticity and neural resilience against aging and Alzheimer's disease (AD)-related pathogenic proteins. Here, we examined the relationship between human genetic variants of KLOTHO and systemic klotho levels - and assessed neuroanatomic correlates of serum klotho in a cohort of healthy older adults. Serum klotho levels were increased with KL-VS heterozygosity, as anticipated. We report, for the first time, that serum klotho levels were paradoxically decreased with KL-VS homozygosity. Further, we found that higher serum klotho levels were associated with measures of greater intrinsic connectivity in key functional networks of the brain vulnerable to aging and AD such as the fronto-parietal and default mode networks. Our findings suggest that elevated klotho promotes a resilient brain, possibly through increased network connectivity of critical brain regions.

Alternate JournalBrain Imaging Behav
PubMed ID27714549
PubMed Central IDPMC5382127
Grant ListK01 AG049152 / AG / NIA NIH HHS / United States
R01 AG048234 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
R01 AG032289 / AG / NIA NIH HHS / United States
R01 NS092918 / NS / NINDS NIH HHS / United States