Cognition Aging
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB90935 | ENA |
REPOSITORIES: ENA
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Project description:Multi-omics analysis highlights the link of aging-related cognitive decline with systemic inflammation and alterations of tissue-maintenance
| PRJNA1289162 | ENA
Project description:Multi-omics analysis highlights the link of aging-related cognitive decline with systemic inflammation and alterations of tissue-maintenance [RRBS]
| PRJNA1302457 | ENA
Project description:Aging-related cognitive decline is associated with changes across different tissues and the gut microbiome, including dysfunction of the gut-brain axis. However, only few studies have linked multi-organ alterations to cognitive decline during aging. Here we report a multi-omics analysis integrating metabolomics, transcriptomics, DNA methylation, and metagenomics data from hippocampus, liver, colon, and fecal samples of mice, correlated with cognitive performance in the Barnes Maze spatial learning task across different age groups. We identified 734 molecular features associated with cognitive rank within individual data layers, of which 227 features remain when integrating all data layers with each other. Among the single-layer predictors, several host and microbial features were highlighted, with host-associated markers being predominant. Host features associated with cognitive function mainly belong to innate and adaptive inflammatory activity (inflammaging) and developmental processes. Our findings suggest that cognitive decline in aging is tightly coupled to systemic, age-associated inflammation, potentially initiated by microbiome-driven gastrointestinal inflammatory activity, emphasizing a link between peripheral tissue alterations and brain function.
2025-12-31 | GSE302188 | GEO
Project description:Aging-related cognitive decline is associated with changes across different tissues and the gut microbiome, including dysfunction of the gut-brain axis. However, only few studies have linked multi-organ alterations to cognitive decline during aging. Here we report a multi-omics analysis integrating metabolomics, transcriptomics, DNA methylation, and metagenomics data from hippocampus, liver, colon, and fecal samples of mice, correlated with cognitive performance in the Barnes Maze spatial learning task across different age groups. We identified 734 molecular features associated with cognitive rank within individual data layers, of which 227 features remain when integrating all data layers with each other. Among the single-layer predictors, several host and microbial features were highlighted, with host-associated markers being predominant. Host features associated with cognitive function mainly belong to innate and adaptive inflammatory activity (inflammaging) and developmental processes. Our findings suggest that cognitive decline in aging is tightly coupled to systemic, age-associated inflammation, potentially initiated by microbiome-driven gastrointestinal inflammatory activity, emphasizing a link between peripheral tissue alterations and brain function.
2025-08-31 | GSE304754 | GEO
Project description:Aging leads to a progressive deterioration in brain function, which will eventually result in cognitive decline and can develop into a dementia. The mechanisms underlying pathological cognitive decline in aging are still poorly understood. The peripheral immune system, as well as the meningeal lymphatic vasculature and the immune cells residing in the brain and meninges, are all affected by aging. Moreover, recent studies have linked the dysfunction of the meningeal lymphatic system and peripheral immunity to accelerated brain aging. We hypothesized that an age-related reduction in CCR7-dependent immune cell egress through the lymphatic vasculature mediates some aspects of aging-associated brain dysfunction, leading to cognitive decline and potentially exacerbating neurodegenerative diseases. Here, we report a reduction in CCR7 expression by meningeal T cells in aged mice and its associated increase in meningeal T-regulatory cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to cognitive impairment. Interestingly, CCR7-deficient mice also presented impaired brain glymphatic function and showed increased amyloid beta (A) deposition when crossed with the 5xFAD transgenic mouse model of Alzheimer’s disease (AD). These results show that the aging-associated decrease in CCR7 expression impacts meningeal immunity, affects different aspects of brain function and exacerbates brain A pathology, highlighting its potential as a pathogenic mechanism for cognitive decline in aging and AD.
2021-03-22 | GSE163725 | GEO
Project description:Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as brain ages is the aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we established a mechanistic link between chronic inflammation and aging microglia, and demonstrated a causal role of aging microglia in neurodegenerative cognitive deficits. Expression of microglial SIRT1 reduces with the aging of microglia. Genetic reduction of microglial SIRT1 elevates IL-1β selectively, and exacerbates cognitive deficits in aging and in transgenic mouse models of frontotemporal dementia (FTD). Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the proximal promoter of IL-1β. Consistent with our findings in mice, selective hypomethylation of IL-1β at two CpG sites are found in normal aging humans and demented patients with tauopathy. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in neurodegenerative diseases. Study of changes related to alterations of SIRT1 levels in microglia of young and aged animals and in models of neurodegenerative dementia
2014-10-01 | E-GEOD-56452 | biostudies-arrayexpress
Project description:The present study combines high resolution imaging, quantitative tissue proteomics, novel goal directed behaviors, and genetic inductions of microglial depletion and accelerated aging to link microglia, synapse, and ECM status across the mesolimbic dopamine system with cognitive aging outcomes.
2024-11-22 | MSV000096508 | MassIVE
Project description:Young blood or plasma and young bone marrow improves cognitive function in aged animals, though the cell type responsible for these regenerative effects remains unknown. This study evaluated the potential of induced pluripotent stem cell-derived mononuclear phagocytes (iMPs) as a therapeutic for age-associated cognitive and neural decline. Aging mice receiving intravenous delivery of iMPs for 3 weeks showed significant improvements in hippocampus dependent cognitive tasks and neural health markers, including increased levels of the synaptic transporter VGLUT1 and decreases in both astrogliosis and activated microglia. Proteomics on plasma and single nuclei RNA sequencing of the hippocampus identified several key aging specific pathways. iMP treatment of aging mice was able to reverse the increases in complement and amyloid pathway proteins, restore a lost subpopulation of hippocampal mossycells, and nearly eliminate a population of activated microglia. These findings suggest that iMPs provide a novel individualized therapeutic strategy to target age-related neural decline.
2025-11-10 | PXD052723 | Pride
Project description:Aging-related cognitive decline, including impairments in spatial orientation and memory, has been linked to dysfunction within the hippocampus and medial entorhinal cortex (MEC). However, the cellular and molecular alterations underlying MEC aging remain poorly understood. Here we show that old mice exhibit a reduced proportion of grid cells and decreased spatial stability. Transcriptomic profiling of the MEC using 10x Genomics Visium technology reveals 1664 differentially expressed genes between young and old mice. Among these, Bglap3 is identified as a marker gene for a subpopulation of Layer III neurons that showed an age-associated reduction in cell number. Chemogenetic silencing of Bglap3+ neurons in young mice impairs spatial tuning of MEC neurons. Together, these findings elucidate cellular and molecular mechanisms contributing to age-related MEC dysfunction and suggest that the loss of Bglap3+ neurons may underlie spatial coding deficits in aging.
2026-09-17 | GSE347650 | GEO
Project description:Epigenetic mechanisms, including histone acetylation, play a key role in learning and memory, with recent evidence of a role in neuronal function in Alzheimer’s disease and Related Dementia (ADRD). Acetyl-CoA sythetase 2 (ACSS2) is central to epigenetics and gene regulation, particularly in neurons, due to their unique metabolic demands and their postmitotic state. ACSS2 can be directly recruited to the nucleus to locally supply acetyl-CoA, and to directly fuel histone acetyltransferases. This gene regulatory mechanism presents a promising avenue for targeted therapeutic interventions in neurodegenerative diseases. Building upon our prior discovery that systemic ACSS2 deletion in mouse impairs memory and reduces immediate early gene expression, we explored whether increasing levels of ACSS2 to boost chromatin processes could protect neurons against disease and age-associated cognitive decline. Given the role of tau in ADRD, we used primary hippocampal neurons that mimic the sporadic development of tau pathology, and the PS19 transgenic mouse model for tau-induced memory decline. We show that ACSS2 upregulation mitigates tau-induced transcriptional alterations, enhances neuronal resilience against tau pathology, improves long-term potentiation, and ameliorates memory deficits. Expanding upon our findings, we investigated ACSS2-dependent epigenetic modifications in aged mice. Our results reveal that increasing histone acetylation through ACSS2 upregulation also improves age-associated memory decline. These findings show that increasing the level of ACSS2 is highly effective in countering age and tau-induced transcriptomic changes, preserving elevated levels of synaptic genes, and thereby safeguards synaptic integrity over time. Our results highlight ACSS2 as a key player in the epigenetic regulation of cognitive aging and ADRD, thus opening exciting prospects for targeted therapeutic strategies aimed at enhancing brain resilience and function.
2026-09-07 | PXD048769 | Pride