ArticleCommunications biology2024
Knockout of the longevity gene Klotho perturbs aging and Alzheimer's disease-linked brain microRNAs and tRNA fragments.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- 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
- Striatal small RNA remodeling in MPTP-induced Parkinson's disease highlights coordinated downregulation of mitochondrial tsRNAs.Frontiers in aging neuroscience · 2026Article
- Mechanisms of Transfer RNA Fragments Functionality Within and Between Cells and Organisms.Cells · 2025Review
- Targeting the Milieu in Neurodegenerative Disease: Time for "Imprecision Medicine"?Aging and disease · 2025Review
- Transcriptomic Response to Neuromuscular Electrical Stimulation in Muscle, Brain, and Plasma EVs in WT and Klotho-Deficient Mice.International journal of molecular sciences · 2025Article
- Emerging roles of transfer RNA fragments in the CNS.Brain : a journal of neurology · 2025Review
- Drivers and mechanisms of cognitive decline in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- SkeletAge: Transcriptomics-based Aging Clock Identifies 26 New Targets in Skeletal Muscle Aging.bioRxiv : the preprint server for biology · 2025Article
- Mapping Current Studies of tRNA Fragments onto Disease Landscape.Biomolecules · 2025Review
- The role of the intestinal microbiome in cognitive decline in patients with kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Aging and sex differences in salt sensitivity of blood pressure.Clinical science (London, England : 1979) · 2025Review
- Deciphering the role of tRNA-derived fragments in neurological and psychiatric disease pathogenesis.Frontiers in cellular neuroscience · 2025Review
- Klotho Protein: A Multifaceted Guardian of Healthy Aging and Its Therapeutic Potential.International journal of nanomedicine · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
Overexpression of the longevity gene Klotho prolongs lifespan, while its knockout shortens lifespan and impairs cognition via perturbation of myelination and synapse formation. However, comprehensive analysis of Klotho knockout effects on mammalian brain transcriptomics is lacking. Here, we report that Klotho knockout alters the levels of aging- and cognition related mRNAs, long non-coding RNAs, microRNAs and tRNA fragments. These include altered neuronal and glial regulators in murine models of aging and Alzheimer's disease and in human Alzheimer's disease post-mortem brains. We further demonstrate interaction of the knockout-elevated tRNA fragments with the spliceosome, possibly affecting RNA processing. Last, we present cell type-specific short RNA-seq datasets from FACS-sorted neurons and microglia of live human brain tissue demonstrating in-depth cell-type association of Klotho knockout-perturbed microRNAs. Together, our findings reveal multiple RNA transcripts in both neurons and glia from murine and human brain that are perturbed in Klotho deficiency and are aging- and neurodegeneration-related.
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