Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging

Jennifer S. Yokoyama, Gabe Marx, Jesse A. Brown, Luke W. Bonham, Dan Wang, Giovanni Coppola, William W. Seeley, Howard J. Rosen, Bruce L. Miller, Joel H. Kramer, Dena B. Dubal

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)391-400
Number of pages10
JournalBrain Imaging and Behavior
Volume11
Issue number2
DOIs
StatePublished - 1 Apr 2017
Externally publishedYes

Keywords

  • Aging
  • Cognition
  • Connectivity
  • Frontal cortex
  • Genetic variation
  • Imaging
  • Klotho
  • Longevity
  • Resilience

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