ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2022
KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07216781 (Evaluating the Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans), which is not on this map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Evaluating the Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans: An Interventional, Non-Placebo-Controlled Pilot Phase Study
Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- 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
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- Klotho as a novel biomarker of attention-deficit hyperactivity disorder and related executive dysfunction.BJPsych open · 2026Article
- Anesthesia, perimortem conditions, and brain harvest method govern the measured metabolome: analysis of substandard samples generates flawed metabolite levels.Oxford open neuroscience · 2026Article
- The Anti-Inflammatory Actions of Soluble Klotho in Brain Aging and Its Main Associated Diseases.International journal of molecular sciences · 2025Review
- Correlation analysis between serum Klotho and cognitive function in diabetes individuals.Diabetology & metabolic syndrome · 2025Article
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- Article
- Amyloid-β positivity is less prevalent in cognitively unimpairedJournal of Alzheimer's disease : JAD · 2024Article
- Review
- A second X chromosome improves cognition in aging male and female mice.bioRxiv : the preprint server for biology · 2024Article
- Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.Nature metabolism · 2023Article
- 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
- Klotho, a longevity factor, improves cognitive function in aging nonhuman primates.Nature aging · 2023Article
- Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.Research square · 2023Article
- X Chromosome Factor Kdm6a Enhances Cognition Independent of Its Demethylase Function in the Aging XY Male Brain.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Differential toxicity profile of secreted and processed α-Klotho expression over mineral metabolism and bone microstructure.Scientific reports · 2023Article
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Frontiers in aging · 2023Article
- Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.Frontiers in aging · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Cognitive deficits are a major biomedical challenge-and engagement of the brain in stimulating tasks improves cognition in aged individuals (Wilson et al., 2002; Gates et al., 2011) and rodents (Aidil-Carvalho et al., 2017), through unknown mechanisms. Whether cognitive stimulation alters specific metabolic pathways in the brain is unknown. Understanding which metabolic processes are involved in cognitive stimulation is important because it could lead to pharmacologic intervention that promotes biological effects of a beneficial behavior, toward the goal of effective medical treatments for cognitive deficits. Here we show using male mice that cognitive stimulation induced metabolic remodeling of the mouse hippocampus, and that pharmacologic treatment with the longevity hormone α-klotho (KL), mediated by its KL1 domain, partially mimicked this alteration. The shared, metabolic signature shared between cognitive stimulation and treatment with KL or KL1 closely correlated with individual mouse cognitive performance, indicating a link between metabolite levels and learning and memory. Importantly, the treatment of mice with KL1, an endogenous circulating factor that more closely mimicked cognitive stimulation than KL, acutely increased synaptic plasticity, a substrate of cognition. KL1 also improved cognition, itself, in young mice and countered deficits in old mice. Our data show that treatments or interventions mimicking the hippocampal metabolome of cognitive stimulation can enhance brain functions. Further, we identify the specific domain by which klotho promotes brain functions, through KL1, a metabolic mimic of cognitive stimulation.
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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.