Region-Specific Transcriptional Signatures of Brain Aging in the Absence of Neuropathology at the Single-cell Level
Rattachement africain : us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Given that age is a significant risk factor for multiple neurodegenerative diseases, investigating normal brain aging may help identify molecular events that may contribute to increased disease risk over time. Single-nucleus RNA sequencing (snRNA-seq) enables analysis of gene expression changes within specific cell-types, potentially offering insights into the molecular mechanisms underlying aging. However, most brain snRNA-Seq datasets used age-matched controls from studies focused on pathological processes and have largely been limited to cortical regions. Therefore, there is a need to investigate the non-pathological aging process in brain regions that are vulnerable to age-related diseases. Here, we report a snRNA-seq study of 6 young (20-30 years) and 7 aged (60-85 years) encompassing four different brain regions: the entorhinal cortex, middle temporal gyrus, subventricular zone, and putamen. We captured over 150,000 nuclei that represented 10 broad cell-types. While we did not find statistically significant differences in cell-type proportions with age, region- and cell-type-specific differential expression analyses identified over 8,000 age-associated genes. Notably, within a given cell-type, most of these associations were region-specific. Functional enrichment analyses of the gene sets for each cell-type-region combination revealed diverse biological processes, including multiple hallmarks of aging, such as proteostasis, interactions with cytokines, vesicular trafficking, metabolism, inflammation, and metal ion homeostasis. Overall, our findings suggest that unique cell-types exhibit distinct transcriptional aging profiles both at the cell-type level and across different brain regions.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Region-Specific Transcriptional Signatures of Brain Aging in the Absence of Neuropathology at the Single-cell Level
- Date Crossref
- 01/08/2023
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
National Institutes of Health Center for Alzheimer's and Related Dementias pays non établi dans la noticeOrganisme public
-
National Institute on Aging pays non établi dans la noticeStructure de recherche
-
Johns Hopkins University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
-
University Medical Center pays non établi dans la noticeÉtablissement de santé
-
Data Tecnica International (United States) pays non établi dans la noticeEntreprise
-
National Institute of Neurological Disorders and Stroke Neurodegenerative Diseases Research Section pays non établi dans la noticeStructure de recherche
-
National Institute of Mental Health Division of Intramural Research pays non établi dans la noticeStructure de recherche
-
Laboratory of Neurogenetics Cell Biology and Gene Expression Section pays non établi dans la noticeStructure de recherche
-
Data Tecnica International LLC pays non établi dans la noticeInstitution
-
DataTecnica LLC pays non établi dans la noticeInstitution
-
Neurodegenerative Diseases Research Unit pays non établi dans la noticeStructure de recherche
Center for Alzheimer's and Related Dementias — National Institutes of Health, National Institute on Aging et Department of Neurology — Johns Hopkins University, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.