Human Brain Cell‐Type‐Specific Aging Clocks Based on Single‐Nuclei Transcriptomics
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.
Authors
- Enikő Zakar‐Polyák (ORCID: https://orcid.org/0000-0001-5655-4940)
- Johan Jakobsson (ORCID: https://orcid.org/0000-0003-0669-7673)
- Éva Renner (ORCID: https://orcid.org/0000-0001-6957-8562)
- Diahann A. M. Atacho (ORCID: https://orcid.org/0000-0002-6158-0235)
- Csaba Kerepesi (ORCID: https://orcid.org/0000-0001-9541-246X)
- Raquel Garza (ORCID: https://orcid.org/0000-0002-2524-3055)
- Chandramouli Muralidharan (ORCID: https://orcid.org/0000-0003-2271-9609)
- Yogita Sharma (ORCID: https://orcid.org/0000-0001-9702-1809)
- A Abbas (ORCID: https://orcid.org/0000-0002-6450-2208)
- Karolina Pircs (ORCID: https://orcid.org/0000-0001-8281-4785)
- Anita Adami (ORCID: https://orcid.org/0000-0002-9421-7942)
- Miklós Palkovits (ORCID: https://orcid.org/0000-0003-0578-0387)
- Jonas Johansson
Institutions
- Semmelweis University (HU)
- Eötvös Loránd University (HU)
- Lund University (SE)
- HUN-REN Institute for Computer Science and Control (HU)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1002/advs.202506109
- Citations
- 1
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- International Center for Genetic Engineering and Biotechnology
- European Commission
- Semmelweis Egyetem
- Magyar Tudományos Akadémia
- Vetenskapsrådet
- Horizon 2020 Framework Programme
- National Research, Development and Innovation Office