@article{9219453bb3ca4104a314b738e64b1144,
title = "Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging",
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{\textquoteright}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.",
keywords = "Aging, Cognition, Connectivity, Frontal cortex, Genetic variation, Imaging, Klotho, Longevity, Resilience",
author = "Yokoyama, {Jennifer S.} and Gabe Marx and Brown, {Jesse A.} and Bonham, {Luke W.} and Dan Wang and Giovanni Coppola and Seeley, {William W.} and Rosen, {Howard J.} and Miller, {Bruce L.} and Kramer, {Joel H.} and Dubal, {Dena B.}",
note = "Funding Information: The authors declare no conflicts of interest directly related to the subject matter of the article. Author Dr. William Seeley has received consulting fees from Bristol-Meyers Squibb. Author Dr. Bruce L. Miller, MD receives grant support from the NIH/NIA and the Centers for Medicare & Medicaid Services (CMS) as grants for the Memory and Aging Center. As an additional disclosure, Dr. Miller serves as Medical Director for the John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; and Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK). Portions of this work are the subject of a provisional patent application held by the Regents of the University of California. Funding Information: This study was funded by several sources. Primary support for data analyses was provided by the Larry L. Hillblom Foundation 2012-A-015-FEL and 2016-A-005-SUP (JSY), AFTD Susan Marcus Memorial Fund Clinical Research Grant (JSY), NIA K01 AG049152 (JSY), Paul Beeson Aging Award NIA AG034531 (DBD), NINDS NS092918 (DBD), the American Federation for Aging Research (DBD), the Glenn Medical Foundation (DBD), and the Coulter-Weeks and Bakar Foundations (DBD). Additional support, including for assembly of cohorts, provided by Hillblom Aging Network (BLM) and NIA AG019724 (HR, WS) and AG032289 (JK). Publisher Copyright: {\textcopyright} 2016, The Author(s).",
year = "2017",
month = apr,
day = "1",
doi = "10.1007/s11682-016-9598-2",
language = "English",
volume = "11",
pages = "391--400",
journal = "Brain Imaging and Behavior",
issn = "1931-7557",
publisher = "Springer New York",
number = "2",
}