Variation in longevity gene KLOTHO is associated with greater cortical volumes

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.

[1]  Eleanor A. Maguire,et al.  CA3 size predicts the precision of memory recall , 2014, Proceedings of the National Academy of Sciences.

[2]  Á. Pascual-Leone,et al.  Causal evidence supporting functional dissociation of verbal and spatial working memory in the human dorsolateral prefrontal cortex , 2014, The European journal of neuroscience.

[3]  L. Mucke,et al.  Life Extension Factor Klotho Enhances Cognition , 2016 .

[4]  Annals of Clinical and Translational Neurology , 2014, Annals of clinical and translational neurology.

[5]  Shenmin Zhang,et al.  Changes in cerebral morphometry and amplitude of low-frequency fluctuations of BOLD signals during healthy aging: correlation with inhibitory control , 2014, Brain Structure and Function.

[6]  C. Abraham,et al.  Biochemical and Functional Characterization of the Klotho-VS Polymorphism Implicated in Aging and Disease Risk* , 2013, The Journal of Biological Chemistry.

[7]  Jeffrey D. Bernstein,et al.  Shared Vulnerability of Two Synaptically-Connected Medial Temporal Lobe Areas to Age and Cognitive Decline: A Seven Tesla Magnetic Resonance Imaging Study , 2013, The Journal of Neuroscience.

[8]  Benjamin Thyreau,et al.  A longitudinal study of age‐ and gender‐related annual rate of volume changes in regional gray matter in healthy adults , 2013, Human brain mapping.

[9]  David A. Bennett,et al.  Gray-matter macrostructure in cognitively healthy older persons: associations with age and cognition , 2013, Brain Structure and Function.

[10]  B. Miller,et al.  Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration , 2013, Proceedings of the National Academy of Sciences.

[11]  J. Grafman,et al.  Dorsolateral prefrontal contributions to human working memory , 2013, Cortex.

[12]  J. Luebke,et al.  The Antiaging Protein Klotho Enhances Oligodendrocyte Maturation and Myelination of the CNS , 2013, The Journal of Neuroscience.

[13]  Angela R. Laird,et al.  Is There “One” DLPFC in Cognitive Action Control? Evidence for Heterogeneity From Co-Activation-Based Parcellation , 2012, Cerebral cortex.

[14]  A. Pfefferbaum,et al.  Visual search and the aging brain: discerning the effects of age-related brain volume shrinkage on alertness, feature binding, and attentional control. , 2013, Neuropsychology.

[15]  A. Simmons,et al.  Is the subcallosal medial prefrontal cortex a common site of atrophy in Alzheimer's disease and frontotemporal lobar degeneration? , 2012, Front. Ag. Neurosci..

[16]  Kenny Q. Ye,et al.  An integrated map of genetic variation from 1,092 human genomes , 2012, Nature.

[17]  M. Kuro-o,et al.  The emerging role of Klotho in clinical nephrology. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[18]  J. Schneider,et al.  Overview and findings from the rush Memory and Aging Project. , 2012, Current Alzheimer research.

[19]  Ming-Chang Chiang,et al.  Enhanced Motor Learning in Older Adults Is Accompanied by Increased Bilateral Frontal and Fronto-Parietal Connectivity , 2012, Brain Connect..

[20]  James C Gee,et al.  Structural Variations in Prefrontal Cortex Mediate the Relationship between Early Childhood Stress and Spatial Working Memory , 2012, The Journal of Neuroscience.

[21]  D. Weinberger,et al.  Common and Differential Pathophysiological Features Accompany Comparable Cognitive Impairments in Medication-Free Patients with Schizophrenia and in Healthy Aging Subjects , 2012, Biological Psychiatry.

[22]  J. Morrison,et al.  The ageing cortical synapse: hallmarks and implications for cognitive decline , 2012, Nature Reviews Neuroscience.

[23]  Menno P. Witter,et al.  A pathophysiological framework of hippocampal dysfunction in ageing and disease , 2011, Nature Reviews Neuroscience.

[24]  Ann K. Shinn,et al.  Abnormal Medial Prefrontal Cortex Resting-State Connectivity in Bipolar Disorder and Schizophrenia , 2011, Neuropsychopharmacology.

[25]  Adam Gazzaley,et al.  In Brief , 2011, Nature Reviews Neuroscience.

[26]  Yong He,et al.  Discrete Neuroanatomical Networks Are Associated with Specific Cognitive Abilities in Old Age , 2011, The Journal of Neuroscience.

[27]  D. Nagaraja,et al.  Association of the functional KL-VS variant of Klotho gene with early-onset ischemic stroke. , 2010, Biochemical and biophysical research communications.

[28]  C. Jack,et al.  Comparing 3 T and 1.5 T MRI for tracking Alzheimer's disease progression with tensor‐based morphometry , 2010, Human brain mapping.

[29]  C. Kenyon.  The genetics of ageing , 2010, Nature.

[30]  Stephen F. Barnes.  The Aging Human Brain , 2010 .

[31]  C. Franceschi,et al.  The frequency of Klotho KL-VS polymorphism in a large Italian population, from young subjects to centenarians, suggests the presence of specific time windows for its effect , 2010, Biogerontology.

[32]  Jordan Grafman,et al.  The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex , 2009, Behavioural Brain Research.

[33]  A. Dale,et al.  Regional rates of neocortical atrophy from normal aging to early Alzheimer disease , 2009, Neurology.

[34]  C. Jack,et al.  Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease , 2009, Brain : a journal of neurology.

[35]  J. Gabrieli,et al.  Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia , 2009, Proceedings of the National Academy of Sciences.

[36]  J. Morris,et al.  The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals , 2008, Cerebral cortex.

[37]  B. Miller,et al.  The neural basis of surface dyslexia in semantic dementia. , 2009, Brain : a journal of neurology.

[38]  M. Kuro-o,et al.  The Klotho gene family and the endocrine fibroblast growth factors , 2008, Current opinion in nephrology and hypertension.

[39]  T. Gotow,et al.  Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice , 2008, Neuroscience.

[40]  B. Browning,et al.  Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. , 2007, American journal of human genetics.

[41]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[42]  C. Kuo,et al.  Augmented Wnt Signaling in a Mammalian Model of Accelerated Aging , 2007, Science.

[43]  Daniel Y. Kimberg,et al.  Power in Voxel-based Lesion-Symptom Mapping , 2007, Journal of Cognitive Neuroscience.

[44]  J. Hinman,et al.  What’s Behind the Decline? The Role of White Matter in Brain Aging , 2007, Neurochemical Research.

[45]  N. Raz,et al.  Differential Aging of the Brain: Patterns, Cognitive Correlates and Modifiers , 2022 .

[46]  Bart Rypma,et al.  Prefrontal modulation of working memory performance in brain injury and disease , 2006, Human brain mapping.

[47]  N. Schuff,et al.  Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease , 2006, Neuroscience Letters.

[48]  Robert H. Paul,et al.  The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan. , 2006, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[49]  J. Hoenderop,et al.  The ß-Glucuronidase Klotho Hydrolyzes and Activates the TRPV5 Channel , 2005, Science.

[50]  Animesh Nandi,et al.  Suppression of Aging in Mice by the Hormone Klotho , 2005, Science.

[51]  I. Deary,et al.  KLOTHO genotype and cognitive ability in childhood and old age in the same individuals , 2005, Neuroscience Letters.

[52]  D. Arking,et al.  Association Between a Functional Variant of the KLOTHO Gene and High-Density Lipoprotein Cholesterol, Blood Pressure, Stroke, and Longevity , 2005, Circulation research.

[53]  Joel H Kramer,et al.  Patterns of Cognitive and Emotional Empathy in Frontotemporal Lobar Degeneration , 2005, Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology.

[54]  Per Capita,et al.  About the authors , 1995, Machine Vision and Applications.

[55]  R. Buckner.  Memory and Executive Function in Aging and AD Multiple Factors that Cause Decline and Reserve Factors that Compensate , 2004, Neuron.

[56]  F. Dick,et al.  Voxel-based lesion–symptom mapping , 2003, Nature Neuroscience.

[57]  B. Mensour,et al.  Neural circuitry underlying voluntary suppression of sadness , 2003, Biological Psychiatry.

[58]  M. Shenton,et al.  Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma , 2002, Nature Neuroscience.

[59]  T. Robbins,et al.  Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET. , 2002, Brain : a journal of neurology.

[60]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[61]  I. Mian,et al.  Association of human aging with a functional variant of klotho , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Á. Pascual-Leone,et al.  The role of the dorsolateral prefrontal cortex during sequence learning is specific for spatial information. , 2001, Cerebral cortex.

[63]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[64]  Edward T. Bullmore,et al.  Prolonged Reaction Time to a Verbal Working Memory Task Predicts Increased Power of Posterior Parietal Cortical Activation , 2000, NeuroImage.

[65]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[66]  F. Chollet,et al.  Cortical motor reorganization in akinetic patients with Parkinson's disease: a functional MRI study. , 2000, Brain : a journal of neurology.

[67]  C. Jack,et al.  Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease , 1998, Neurology.

[68]  M. Kuro-o,et al.  Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein 1 , 1998, FEBS letters.

[69]  R. Nagai,et al.  Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. , 1998, Biochemical and biophysical research communications.

[70]  Tadashi Kaname,et al.  Mutation of the mouse klotho gene leads to a syndrome resembling ageing , 1997, Nature.

[71]  D. Head,et al.  Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. , 1997, Cerebral cortex.

[72]  D. A. Kenny,et al.  The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. , 1986, Journal of personality and social psychology.

[73]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.