Academic Journal
Epigenetic and 3D genome reprogramming during the aging of the human hippocampus.
| Τίτλος: | Epigenetic and 3D genome reprogramming during the aging of the human hippocampus. |
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| Συγγραφείς: | Zemke NR; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Lee S; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Mamde S; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Yang B; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Berchtold N; Department of Anatomy and Neurobiology, University of California, Irvine School of Medicine, Irvine, CA, USA.; Immunis Inc., Irvine, CA, USA., Garduño BM; Department of Anatomy and Neurobiology, University of California, Irvine School of Medicine, Irvine, CA, USA., Indralingam HS; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Bartosik WM; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Lau PK; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Dong K; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA., Hsu E; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Department of Biochemistry and Molecular Medicine and the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Yang A; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Tani Y; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Chen C; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Zeng Q; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Ajith V; Department of Anatomy and Neurobiology, University of California, Irvine School of Medicine, Irvine, CA, USA., Tong L; Department of Anatomy and Neurobiology, University of California, Irvine School of Medicine, Irvine, CA, USA., Seng C; Department of Genetics, The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Li D; Department of Genetics, The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA., Wang T; Department of Genetics, The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA., Zhou J; Arc Institute, Palo Alto, CA, USA.; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA., Ecker JR; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA, USA., Glass CK; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Department of Medicine, University of California, School of Medicine, La Jolla, CA, USA., Cotman CW; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.; Department of Neurology, University of California, Irvine School of Medicine, Irvine, CA, USA., Xu X; Department of Anatomy and Neurobiology, University of California, Irvine School of Medicine, Irvine, CA, USA.; The Center for Neural Circuit Mapping, University of California, Irvine, CA, USA., Ren B; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; New York Genome Center, New York, NY, USA.; Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. |
| Πηγή: | Science (New York, N.Y.) [Science] 2026 Jul 23; Vol. 393 (6809), pp. eadt8307. Date of Electronic Publication: 2026 Jul 23. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| Imprint Name(s): | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
| Ιατρικοί όροι (MeSH): | Aging*/genetics , Cellular Reprogramming*/genetics , Hippocampus*/metabolism , Hippocampus*/cytology , Hippocampus*/physiology , Epigenesis, Genetic* , Genome, Human*, Astrocytes/metabolism ; Astrocytes/physiology ; Chromatin/ultrastructure ; Microglia/metabolism ; Microglia/physiology ; Aged ; Humans ; Middle Aged ; DNA Methylation ; Gene Expression Regulation |
| Περίληψη: | Changes in gene expression have been observed in the aging human brain, but our understanding of the underlying regulatory mechanisms remains limited. To unravel these complexities, we analyzed single-nucleus gene expression, chromatin accessibility, DNA methylation, and three-dimensional (3D) chromatin architecture from human hippocampal tissues spanning the adult lifespan. We identified both linear and nonlinear dynamic gene regulatory programs during aging. Between the ages of 50 to 75, embryonic yolk sac-derived microglia were depleted and replaced by cells resembling peripheral blood monocyte-derived microglia. Hippocampal astrocytes decreased substantially with age, including those regulating synaptic transmission. Across cell types, 3D genome architecture underwent global erosion. Our analysis provides insights for how altered gene regulatory programs promote cell type-specific aging phenotypes in the human brain. |
| Σχόλια: | Update of: bioRxiv. 2024 Oct 17:2024.10.14.618338. doi: 10.1101/2024.10.14.618338.. (PMID: 39463924) |
| Substance Nomenclature: | 0 (Chromatin) |
| Entry Date(s): | Date Created: 20260723 Date Completed: 20260723 Latest Revision: 20260728 |
| Update Code: | 20260728 |
| DOI: | 10.1126/science.adt8307 |
| PMID: | 42490474 |
| Βάση Δεδομένων: | MEDLINE |
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