ArticleNPJ aging and mechanisms of disease2021
Klotho inhibits neuronal senescence in human brain organoids.
Article in NPJ aging and mechanisms of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Culture-specific transcriptional drifts limit the fidelity of organoid infection models.PLoS pathogens · 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
- Investigating the protective and therapeutic potential of new generation antioxidant combinations in the brain: an experimental aging model.Biogerontology · 2026Article
- Klotho in aging and diseases: molecular features, expressions, and functional implications.Molecular and cellular biochemistry · 2026Review
- Mitochondrial dysfunction in cellular senescence: a bridge to neurodegenerative disease.npj aging · 2025Review
- Enhanced U-Net-Based Deep Learning Model for Automated Segmentation of Organoid Images.Bioengineering (Basel, Switzerland) · 2025Article
- Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025Review
- Immunosenescence and organoids: pathophysiology and therapeutic opportunities.Immunity & ageing : I & A · 2025Review
- Drivers and mechanisms of cognitive decline in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- p300 inhibition delays premature cellular senescence.npj aging · 2025Article
- Review
- Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity.Molecular brain · 2025Article
- Choroid Plexus Pathophysiology.Annual review of pathology · 2025Review
- A Roadmap for Selecting and Utilizing Optimal Features in scRNA Sequencing Data Analysis for Stem Cell Research: A Comprehensive Review.International journal of stem cells · 2024Review
- Review
- Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2.Science advances · 2024Article
- Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration.Nature aging · 2024Review
- Protocol for generating embedding-free brain organoids enriched with oligodendrocytes.STAR protocols · 2023Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is a major risk factor for many neurodegenerative diseases. Klotho (KL) is a glycosylated transmembrane protein that is expressed in the choroid plexus and neurons of the brain. KL exerts potent anti-aging effects on multiple cell types in the body but its role in human brain cells remains largely unclear. Here we show that human cortical neurons, derived from human pluripotent stem cells in 2D cultures or in cortical organoids, develop the typical hallmarks of senescent cells when maintained in vitro for prolonged periods of time, and that moderate upregulation or repression of endogenous KL expression in cortical organoids inhibits and accelerates senescence, respectively. We further demonstrate that KL expression alters the expression of senescence-associated genes including, extracellular matrix genes, and proteoglycans, and can act in a paracrine fashion to inhibit neuronal senescence. In summary, our results establish an important role for KL in the regulation of human neuronal senescence and offer new mechanistic insight into its role in human brain aging.
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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.