Muralidharan, Chandramouli and Zakar-Polyák, Enikő and Adami, Anita and Abbas, Anna Anoir and Sharma, Yogita and Garza, Raquel and Johansson, Jenny G and Atacho, Diahann A M and Dobolyiné Renner, Éva and Palkovits, Miklós and Kerepesi, Csaba and Jakobsson, Johan and Pircs, Karolina Milena (2025) Human Brain Cell-Type-Specific Aging Clocks Based on Single-Nuclei Transcriptomics. ADVANCED SCIENCE, 12 (43). ISSN 2198-3844 10.1002/advs.202506109

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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.

Item Type:	Article
Uncontrolled Keywords:	Biological Clocks; Aging clocks; human brain aging; single nuclei sequencing; transcriptomic clocks;
Subjects:	Q Science > QA Mathematics and Computer Science > QA75 Electronic computers. Computer science / számítástechnika, számítógéptudomány
Divisions:	Artificial Intelligence Laboratory
SWORD Depositor:	MTMT Injector
Depositing User:	MTMT Injector
Date Deposited:	13 Jan 2026 16:16
Last Modified:	13 Jan 2026 16:16
URI:	https://eprints.sztaki.hu/id/eprint/11054

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