Dataset Information

Variation in longevity gene KLOTHO is associated with greater cortical volumes.

ABSTRACT:

Objective

Identifying genetic variation associated with brain structures in aging may elucidate new biologic mechanisms underlying resilience to cognitive decline. We investigated whether carrying one copy of the protective haplotype "KL-VS" in longevity gene KLOTHO (KL) is associated with greater gray matter volume in healthy human aging compared to carrying no copies.

Methods

We performed unbiased whole-brain analysis in cognitively normal older adults from two independent cohorts to assess the relationship between KL-VS and gray matter volume using voxel-based morphometry.

Results

We found that KL-VS heterozygosity was associated with greater volume in right dorsolateral prefrontal cortex (rDLPFC). Because rDLPFC is important for executive function, we analyzed working memory and processing speed in individuals. KL-VS heterozygosity was associated with enhanced executive function. Larger rDLPFC volume correlated with better executive function across the lifespan examined. Statistical analysis suggested that volume partially mediates the effect of genotype on cognition.

Interpretation

These results suggest that variation in KL is associated with bigger brain volume and better function.

SUBMITTER: Yokoyama JS

PROVIDER: S-EPMC4369272 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Publications

Variation in longevity gene KLOTHO is associated with greater cortical volumes.

Yokoyama Jennifer S JS Sturm Virginia E VE Bonham Luke W LW Klein Eric E Arfanakis Konstantinos K Yu Lei L Coppola Giovanni G Kramer Joel H JH Bennett David A DA Miller Bruce L BL Dubal Dena B DB

Annals of clinical and translational neurology 20150126 3

<h4>Objective</h4>Identifying genetic variation associated with brain structures in aging may elucidate new biologic mechanisms underlying resilience to cognitive decline. We investigated whether carrying one copy of the protective haplotype "KL-VS" in longevity gene KLOTHO (KL) is associated with greater gray matter volume in healthy human aging compared to carrying no copies.<h4>Methods</h4>We performed unbiased whole-brain analysis in cognitively normal older adults from two independent cohor ...[more]

PMID: 25815349

Similar Datasets

Project description:BackgroundLongevity gene klotho (KL) is associated with age-related phenotypes including lifespan, cardiometabolic disorders, cognition, and brain morphology, in part, by conferring protection against inflammation. We hypothesized that the KL/inflammation association might be altered in the presence of psychiatric stress and operate via epigenetic pathways. We examined KL polymorphisms, and their interaction with posttraumatic stress disorder (PTSD) symptoms, in association with KL DNA methylation in blood. We further examined KL DNA methylation as a predictor of longitudinal changes in a peripheral biomarker of inflammation (C-reactive protein; CRP).MethodsThe sample comprised 309 white non-Hispanic military veterans (93.5 % male; mean age: 32 years, range: 19-65; 30 % PTSD per structured diagnostic interview); 111 were reassessed approximately two years later.ResultsAnalyses revealed a methylation quantitative trait locus at rs9527025 (C370S, previously implicated in numerous studies of aging) in association with a Cytosine-phosphate-Guanine site (cg00129557; B = -.65, p = 1.29 X 10-20), located within a DNase hypersensitivity site in the body of KL. There was also a rs9527025 x PTSD severity interaction (B = .004, p = .035) on methylation at this locus such that the minor allele was associated with reduced cg00129557 methylation in individuals with few or no PTSD symptoms while this effect was attenuated in those with elevated levels of PTSD. Path models revealed that methylation at cg00129557 was inversely associated with CRP over time (B = -.14, p = .005), controlling for baseline CRP. There was also an indirect effect of rs9527025 X PTSD on subsequent CRP via cg00129557 methylation (indirect B = -.002, p = .033).ConclusionsResults contribute to our understanding of the epigenetic correlates of inflammation in PTSD and suggest that KL methylation may be a mechanism by which KL genotype confers risk vs. resilience to accelerated aging in those experiencing traumatic stress.

Dataset Information

Variation in longevity gene KLOTHO is associated with greater cortical volumes.

Objective

Methods

Results

Interpretation

Publications

Variation in longevity gene KLOTHO is associated with greater cortical volumes.

Similar Datasets

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