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- Title
Variation in longevity gene KLOTHO is associated with greater cortical volumes.
- Authors
Yokoyama, Jennifer S.; Sturm, Virginia E.; Bonham, Luke W.; Klein, Eric; Arfanakis, Konstantinos; Yu, Lei; Coppola, Giovanni; Kramer, Joel H.; Bennett, David A.; Miller, Bruce L.; Dubal, Dena B.
- 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.
- Subjects
GENETICS of longevity; COGNITION; AGING; BRAIN research; HETEROZYGOSITY
- Publication
Annals of Clinical & Translational Neurology, 2015, Vol 2, Issue 3, p215
- ISSN
2328-9503
- Publication type
Article
- DOI
10.1002/acn3.161