Aging-related Transcriptomic Changes with Spatial Resolution in the Human Prefrontal Cortex.
| Title: | Aging-related Transcriptomic Changes with Spatial Resolution in the Human Prefrontal Cortex. |
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| Authors: | Rai A; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Iatrou A; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Arzeta IV; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Bartlett AL; Harvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA.; Banahan J; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Desai V; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Pantano L; Harvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA.; Castanho I; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Yeganeh PN; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Ploumakis A; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Wang S; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; de Amaral AA; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Kalavros N; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Nagalakshmi SU; Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Tsvetkov P; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Berretta S; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.; Solomon IH; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.; Hide W; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02215, USA.; Vlachos IS; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02215, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Slack FJ; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02215, USA.; Ozdemir R; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Sui SH; Harvard Chan Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02215, USA.; Daskalakis NP; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Mavrikaki M; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.; Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02215, USA. |
| Source: | BioRxiv : the preprint server for biology [bioRxiv] 2026 Jan 12. Date of Electronic Publication: 2026 Jan 12. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| Abstract: | The human prefrontal cortex (PFC), whose laminar organization is essential for cognitive function, is among the first regions to show age-related functional decline1,2. Single-cell sequencing studies revealed cell type-dependent aging effects but lacked spatial specificity3-6. Spatial transcriptomics (ST) advanced our molecular understanding of the human PFC7, yet whether aging-driven changes differ across PFC layers remains unclear. Here, we performed whole-transcriptome ST on postmortem PFC from 37 individuals across the adult lifespan. We mapped cortical layers and revealed aging mechanisms across layers. This represents one of the largest and most comprehensive lifespan ST analysis of the human PFC brain, offering crucial insight into how the brain ages and identifying potential molecular targets to mitigate cognitive aging and extend healthspan. |
| Competing Interests: | All other authors declare no conflicts of interest. |
| Grant Information: | P30 CA006516 United States CA NCI NIH HHS; R01 AG079799 United States AG NIA NIH HHS; R01 AG082093 United States AG NIA NIH HHS; R01 MH133268 United States MH NIMH NIH HHS |
| Entry Date(s): | Date Created: 20260206 Date Completed: 20260209 Latest Revision: 20260209 |
| Update Code: | 20260209 |
| PubMed Central ID: | PMC12871360 |
| DOI: | 10.64898/2026.01.12.698703 |
| PMID: | 41648412 |
| Database: | MEDLINE |
Journal Article; Preprint