ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Human Brain Cell-Type-Specific Aging Clocks Based on Single-Nuclei Transcriptomics.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Novel cell markers with altered expression in brain aging and Alzheimer's disease: A review.IBRO neuroscience reports · 2026Article
- Hippocampal snRNA-seq in Collaborative Cross reveals molecular signatures of cognitive resilience independent of chronological aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The OmniAge compendium of aging omic biomarkers links mitotic clocks to clonal hematopoiesis and causality.Nature communications · 2026Article
- From aging to Alzheimer's disease: concordant brain DNA methylation changes in late life.Genome medicine · 2026Article
- Plasma proteomic signatures of cellular aging predict human disease.Nature medicine · 2026Article
- Investigating the Causal Links between the Aging Process and Alzheimer's Disease Pathogenesis.International journal of stem cells · 2026Review
- Cellular Aging Signatures in the Plasma Proteome Record Human Health and Disease.bioRxiv : the preprint server for biology · 2026Article
- The embedding of stress: mitophagy as a mechanism for the central nervous system (CNS) programming and lifelong disease vulnerability.Frontiers in cell and developmental biology · 2026Review
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- Human Brain Cell-Type-Specific Aging Clocks Based on Single-Nuclei Transcriptomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Aging is the primary risk factor for most neurodegenerative diseases, yet the cell-type-specific progression of brain aging remains poorly understood. Here, human cell-type-specific transcriptomic aging clocks are developed using high-quality single-nucleus RNA sequencing data from post mortem human prefrontal cortex tissue of 31 donors aged 18-94 years, encompassing 73,941 high-quality nuclei. Distinct transcriptomic changes are observed across major cell types, including upregulation of inflammatory response genes in microglia from older samples. Aging clocks trained on each major cell type accurately predict chronological age, capture biologically relevant pathways, and remain robust in independent single-nucleus RNA-sequencing datasets, underscoring their broad applicability. Notably, cell-type-specific age acceleration is identified in individuals with Alzheimer's disease and schizophrenia, suggesting altered aging trajectories in these conditions. These findings demonstrate the feasibility of cell-type-specific transcriptomic clocks to measure biological aging in the human brain and highlight potential mechanisms of selective vulnerability in neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.