ArticleAnnals of clinical and translational neurology2015
Variation in longevity gene KLOTHO is associated with greater cortical volumes.
Article in Annals of clinical and translational neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- KL∗VS heterozygosity reduces brain amyloid in asymptomatic at-risk APOE∗4 carriers.Neurobiology of aging · 2021Pooled it
- Understanding brain resilience in superagers: a systematic review.Neuroradiology · 2021Pooled it
- Longevity Factor Klotho and Resistance to Cognitive Deficits in Individuals with Parkinson's Disease and in an α-Synuclein Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Humanized Klotho haplotypes cause widespread transcriptomic changes in mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Elevated plasma klotho levels attenuate Alzheimer's disease pathologies and cognitive decline in APOE ε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Klotho as a novel biomarker of attention-deficit hyperactivity disorder and related executive dysfunction.BJPsych open · 2026Article
- Grip strength as a systems biomarker of aging: neuromuscular junction constraints and biomarker decoupling in gene therapy.Frontiers in aging · 2026Article
- KLOTHO-VS heterozygosity, α-klotho protein levels and cognitive performance in Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Aerobic exercise-induced changes in fluid biomarkers in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Impact ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Amyloid-β positivity is less prevalent in cognitively unimpairedJournal of Alzheimer's disease : JAD · 2024Article
- KLOTHO KL-VS heterozygosity is associated with diminished age-related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Importance of α-Klotho in Depression and Cognitive Impairment and Its Connection to Glutamate Neurotransmission-An Up-to-Date Review.International journal of molecular sciences · 2023Review
- Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice.Nature aging · 2023Article
- Longevity factor klotho enhances cognition in aged nonhuman primates.Nature aging · 2023Article
- Targeting neuroendocrine abnormalities in Parkinson's disease with exercise.Frontiers in neuroscience · 2023Article
- Relationships between serum Klotho concentrations and cognitive performance among older chronic kidney disease patients with albuminuria in NHANES 2011-2014.Frontiers in endocrinology · 2023Article
- The Interrelated Multifactorial Actions of Cortisol and Klotho: Potential Implications in the Pathogenesis of Parkinson's Disease.Brain sciences · 2022Review
- Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden.JAMA network open · 2022Article
- KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveIdentifying 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.
methodsWe 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.
resultsWe 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.
interpretationThese results suggest that variation in KL is associated with bigger brain volume and better function.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.