ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
What it found
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Who cites it
91 citing papers in PubMed, 168 citations in OpenAlex.
- Low serum klotho concentration is associated with worse cognition, psychological components of frailty, dependence, and falls in nursing home residents.Scientific reports · 2021Trial
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- Klotho Function in Neurogenesis and Oligodendrogenesis: A Mini-Review Update.Journal of molecular neuroscience : MN · 2026Review
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Sex-specific association between serum α-klotho levels and sleep disturbances in the elderly: a cross-sectional study.European journal of medical research · 2025Article
- Non-linear relationship between serum α-Klotho and suicide attempt: evidence from a large never-smoking population.BMC psychiatry · 2025Article
- Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity.Molecular brain · 2025Article
- Uric acid mediates the association between testosterone and α-Klotho among males: results from the NHANES 2013-2016.International urology and nephrology · 2025Article
- Association between Klotho levels in cerebrospinal fluid and choroid plexus enlargement in neurodegeneration.Frontiers in aging neuroscience · 2025Article
- Demyelination and impaired oligodendrogenesis in the corpus callosum following lead exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Article
- Review
- 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
- Knockout of the longevity gene Klotho perturbs aging and Alzheimer's disease-linked brain microRNAs and tRNA fragments.Communications biology · 2024Article
- Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.International journal of molecular sciences · 2024Review
- Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease-a comprehensive review from the ERA CKD-MBD working group.Clinical kidney journal · 2024Article
- Oligodendrocyte progenitor cells in Alzheimer's disease: from physiology to pathology.Translational neurodegeneration · 2023Review
- Klotho increases antioxidant defenses in astrocytes and ubiquitin-proteasome activity in neurons.Scientific reports · 2023Article
- Evidence That DDR1 Promotes Oligodendrocyte Differentiation during Development and Myelin Repair after Injury.International journal of molecular sciences · 2023Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
We have previously shown that myelin abnormalities characterize the normal aging process of the brain and that an age-associated reduction in Klotho is conserved across species. Predominantly generated in brain and kidney, Klotho overexpression extends life span, whereas loss of Klotho accelerates the development of aging-like phenotypes. Although the function of Klotho in brain is unknown, loss of Klotho expression leads to cognitive deficits. We found significant effects of Klotho on oligodendrocyte functions, including induced maturation of rat primary oligodendrocytic progenitor cells (OPCs) in vitro and myelination. Phosphoprotein analysis indicated that Klotho's downstream effects involve Akt and ERK signal pathways. Klotho increased OPC maturation, and inhibition of Akt or ERK function blocked this effect on OPCs. In vivo studies of Klotho knock-out mice and control littermates revealed that knock-out mice have a significant reduction in major myelin protein and gene expression. By immunohistochemistry, the number of total and mature oligodendrocytes was significantly lower in Klotho knock-out mice. Strikingly, at the ultrastructural level, Klotho knock-out mice exhibited significantly impaired myelination of the optic nerve and corpus callosum. These mice also displayed severe abnormalities at the nodes of Ranvier. To decipher the mechanisms by which Klotho affects oligodendrocytes, we used luciferase pathway reporters to identify the transcription factors involved. Together, these studies provide novel evidence for Klotho as a key player in myelin biology, which may thus be a useful therapeutic target in efforts to protect brain myelin against age-dependent changes and promote repair in multiple sclerosis.
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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.