ArticleScience translational medicine2013
Molecular mechanism for age-related memory loss: the histone-binding protein RbAp48.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Transcriptional signatures of brain aging and Alzheimer's disease: What are our rodent models telling us?Behavioural brain research · 2017Pooled it
- Genetic variants in a 'cAMP element binding protein' (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals.Neurobiology of aging · 2014Pooled it
- Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults.Nature neuroscience · 2014Trial
- Epigenetic Mechanisms in Perioperative Medicine: From Neuroinflammation and NETosis to Organ Dysfunction and Precision Therapeutics.Biomedicines · 2026Review
- The dual role of ATF4 in neurons: from stress adaptation to therapeutic intervention.Frontiers in molecular neuroscience · 2026Review
- Inhibition of histone lysine demethylase restores learning and memory in aged mice.bioRxiv : the preprint server for biology · 2025Article
- Chronic stress contributes to long-term isoflurane anesthesia-induced cognitive dysfunction via histone acetylation modulated by RbAp48-HDAC2 in male mice.Journal of anesthesia and translational medicine · 2025Article
- Age-Dependent Changes in Taurine, Serine, and Methionine Release in the Frontal Cortex of Awake Freely-Moving Rats: A Microdialysis Study.Life (Basel, Switzerland) · 2025Article
- Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review).International journal of molecular medicine · 2024Review
- Article
- Taurine deficiency as a driver of aging.Science (New York, N.Y.) · 2023Article
- The consequences of sleep deprivation on cognitive performance.Neurosciences (Riyadh, Saudi Arabia) · 2023Review
- Anatomical biology guides a search for nutrients for the aging brain.Molecular aspects of medicine · 2023Review
- DLX1 and the NuRD complex cooperate in enhancer decommissioning and transcriptional repression.Development (Cambridge, England) · 2022Article
- Neurobiological Highlights of Cognitive Impairment in Psychiatric Disorders.International journal of molecular sciences · 2022Review
- Deep learning of MRI contrast enhancement for mapping cerebral blood volume from single-modal non-contrast scans of aging and Alzheimer's disease brains.Frontiers in aging neuroscience · 2022Article
- Mitochondrial aconitase 1 regulates age-related memory impairment via autophagy/mitophagy-mediated neural plasticity in middle-aged flies.Aging cell · 2021Article
- Chromatin Remodeling in the Brain-aInternational journal of molecular sciences · 2021Review
- Neurochemical and Cognitive Beneficial Effects of Moderate Physical Activity and Catechin in Aged Rats.Antioxidants (Basel, Switzerland) · 2021Article
- Sericin modulates learning and memory behaviors by tuning of antioxidant, inflammatory, and apoptotic markers in the hippocampus of aged mice.Molecular biology reports · 2021Article
11 more citing papers are in PubMed but not listed here.
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Abstract
To distinguish age-related memory loss more explicitly from Alzheimer's disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD. Using expression in the EC for normalization, we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain. Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation. Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation. Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention.
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