ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2023
X Chromosome Factor Kdm6a Enhances Cognition Independent of Its Demethylase Function in the Aging XY Male Brain.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2023. 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, 25 citations in OpenAlex.
- Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms.Biochemical Society transactions · 2026Review
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Epigenetic and transcriptomic alterations precede amyloidosis in the Alzheimer's disease AppScientific reports · 2025Article
- Strategies for studying sex differences in brain aging.Trends in genetics : TIG · 2025Review
- Altered immune response is associated with sex difference in vulnerability to Alzheimer's disease in human prefrontal cortex.Brain pathology (Zurich, Switzerland) · 2025Article
- Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks.Open biology · 2024Review
- The neuron-specific IIS/FOXO transcriptome in aged animals reveals regulatory mechanisms of cognitive aging.eLife · 2024Article
- Male-specific behavioral and transcriptomic changes in agingiScience · 2024Article
- Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The impact of chromosomal sex on cardiometabolic health and disease.Trends in endocrinology and metabolism: TEM · 2023Review
- Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer's disease.Journal of neuroinflammation · 2023Article
- Neurobiology of Aging: New Insights From Across the Research Spectrum.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer's disease.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Males exhibit shorter life span and more cognitive deficits, in the absence of dementia, in aging human populations. In mammals, the X chromosome is enriched for neural genes and is a major source of biologic sex difference, in part, because males show decreased expression of select X factors (XY). While each sex (XX and XY) harbors one active X due to X chromosome inactivation in females, some genes, such as Kdm6a, transcriptionally escape silencing in females-resulting in lower transcript levels in males. Kdm6a is a known histone demethylase (H3K27me2/3) with multiple functional domains that is linked with synaptic plasticity and cognition. Whether elevating Kdm6a could benefit the aged male brain and whether this requires its demethylase function remains unknown. We used lentiviral-mediated overexpression of the X factor in the hippocampus of aging male mice and tested their cognition and behavior in the Morris water-maze. We found that acutely increasing Kdm6a-in a form without demethylase function-selectively improved learning and memory, in the aging XY brain, without altering total activity or anxiety-like measures. Further understanding the demethylase-independent downstream mechanisms of Kdm6a may lead to novel therapies for treating age-induced cognitive deficits in both sexes.
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Registered trials
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