ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 125 papers.
What it found
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Who cites it
125 citing papers in PubMed, 200 citations in OpenAlex.
- Effects of Aerobic Exercise Training on Systemic Biomarkers and Cognition in Late Middle-Aged Adults at Risk for Alzheimer's Disease.Frontiers in endocrinology · 2021Trial
- Hyperbranched poly(β-amino ester)s-mediated delivery of engineered Klotho mRNA rescues senescence and restores cellular homeostasis in aged and Klotho deficient iMSCs.Drug delivery and translational research · 2026Article
- Distinct effects of aging and klotho deletion on the choroid plexus.GeroScience · 2026Article
- Gene deletion of Klotho in the dentate gyrus does not affect the number of adult-born granule cells.Scientific reports · 2026Article
- 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
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- Reduced serum Klotho in chronic schizophrenia: diagnostic value and association with cognitive impairment.Frontiers in psychiatry · 2026Article
- Serum klotho levels modify the positive relationship of depression and all-cause mortality risk.Scientific reports · 2025Article
- The first 25 years of the Northwestern University SuperAging Program.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- 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
- Serum Klotho levels and epilepsy among U.S. adults in the NHANES 2013-2016: a cross-sectional study.Scientific reports · 2025Article
- Aging activates escape of the silent X chromosome in the female mouse hippocampus.Science advances · 2025Article
- Review
- Article
- Relationship between klotho, neurotrophic factors (BDNF, NGF, GDNF) and cognitive functions in patients with bipolar disorder.BMC psychiatry · 2025Article
- Association between Klotho levels in cerebrospinal fluid and choroid plexus enlargement in neurodegeneration.Frontiers in aging neuroscience · 2025Article
- Lack of association between common polymorphisms associated with successful aging and longevity in the population of Sardinian Blue Zone.Scientific reports · 2024Article
- Enhanced Therapeutic Effects of Human Mesenchymal stem Cells Transduced with Secreted Klotho in a Murine Experimental Autoimmune Encephalomyelitis Model.Molecular neurobiology · 2024Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Aging is the principal demographic risk factor for Alzheimer disease (AD), the most common neurodegenerative disorder. Klotho is a key modulator of the aging process and, when overexpressed, extends mammalian lifespan, increases synaptic plasticity, and enhances cognition. Whether klotho can counteract deficits related to neurodegenerative diseases, such as AD, is unknown. Here we show that elevating klotho expression decreases premature mortality and network dysfunction in human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD. Increasing klotho levels prevented depletion of NMDA receptor (NMDAR) subunits in the hippocampus and enhanced spatial learning and memory in hAPP mice. Klotho elevation in hAPP mice increased the abundance of the GluN2B subunit of NMDAR in postsynaptic densities and NMDAR-dependent long-term potentiation, which is critical for learning and memory. Thus, increasing wild-type klotho levels or activities improves synaptic and cognitive functions, and may be of therapeutic benefit in AD and other cognitive disorders.
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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.