Title | Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Yokoyama JS, Marx G, Brown JA, Bonham LW, Wang D, Coppola G, Seeley WW, Rosen HJ, Miller BL, Kramer JH, Dubal DB |
Journal | Brain Imaging Behav |
Volume | 11 |
Issue | 2 |
Pagination | 391-400 |
Date Published | 2017 04 |
ISSN | 1931-7565 |
Keywords | Aged, Aging, Biomarkers, Connectome, Female, Genetic Markers, Glucuronidase, Humans, Male, Nerve Net, Polymorphism, Single Nucleotide, Reproducibility of Results, Sensitivity and Specificity, Temporal Lobe, Tissue Distribution |
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. |
DOI | 10.1007/s11682-016-9598-2 |
Alternate Journal | Brain Imaging Behav |
PubMed ID | 27714549 |
PubMed Central ID | PMC5382127 |
Grant List | K01 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 |