期刊
BRAIN IMAGING AND BEHAVIOR
卷 11, 期 2, 页码 391-400出版社
SPRINGER
DOI: 10.1007/s11682-016-9598-2
关键词
Aging; Cognition; Genetic variation; Longevity; Resilience; Klotho; Imaging; Connectivity; Frontal cortex
类别
资金
- Larry L. Hillblom Foundation [2012-A-015-FEL, 2016-A-005-SUP]
- AFTD Susan Marcus Memorial Fund Clinical Research Grant
- NIA [K01 AG049152, AG019724, AG032289]
- Paul Beeson Aging Award [NIA AG034531]
- NINDS [NS092918]
- American Federation for Aging Research
- Glenn Medical Foundation
- Coulter-Weeks Foundation
- Bakar Foundation
- Hillblom Aging Network
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.
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