همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Age-Related Gene Expression Changes in Microglia: Insights from the Nygen platform and Brain-Aging Atlas

نویسندگان :

Anahita Esmaeili-Mehr¹ َAygin Zabtkar² Seyed abolhassan Shahzade Fazeli³ Amir Amiri-Yekta⁴ Yaser Tahmtani⁵

1- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran Department of Molecular Cell Biology-Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran 2- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research, Tehran, Iran Department of Molecular Cell Biology-Genetics, Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran 3- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Ira 4- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Ira 5- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

کلمات کلیدی :

Brain Aging،Neurodegeneration،Klhdc4،Adamtsl1،Kcna1

چکیده :

Aging is characterized by the accumulation of molecular and cellular damage over an organism’s lifespan, leading to physical deterioration and an increased risk of diseases (Filipa Gaspar-Silva et al., 2023). Brain aging involves physiological, structural, and functional changes that contribute to cognitive decline and the risk of neurodegenerative diseases (Ana Cordeiro et al., 2024). Microglia, as key non-neuronal cells, perform immune surveillance, synaptic pruning, and debris clearance, playing an essential role in maintaining neural health (William E. Allen et al., 2023). In this study, we used data from the Brain-aging-atlas on the Nygen platform, a comprehensive resource of single-cell transcriptomic data, to investigate aging-associated changes in the brain. This dataset includes gene expression profiles, spatial distributions, and pathway-level insights across various brain cell types, including neurons, astrocytes, and microglia, sampled from the frontal cortex and striatum of young (4 weeks) and aged (90 weeks) mice. Differential expression analysis revealed three key differentially expressed genes (DEGs) in aged microglia: Adamtsl1 (fold change: 74.47, score: 0.965), Kcna1 (fold change: 56.52, score: 0.964), and Klhdc4 (fold change: 53.05, score: 0.965), highlighting significant molecular changes with aging. ADAMTSL1 is a secreted glycoprotein in the ADAMTS family, playing a key role in extracellular matrix (ECM) organization, synaptic maintenance, and cellular adhesion. A GWAS study identified it as a significant genetic variant linked to Alzheimer’s and Parkinson’s diseases (Gabel et al., 2018). KCNA1, a voltage-gated potassium channel, is essential for neuronal excitability and synaptic transmission. RNA editing of KCNA1 by ADAR2 has been associated with Alzheimer’s disease and neuronal signaling dysregulation during aging (Tassinari et al., 2023). KLHDC4 was significantly upregulated in aged microglia, indicating involvement in ubiquitin signaling, innate immunity regulation, and lysosomal and autophagy pathways, all linked to neurodegenerative processes (Aguilan et al., 2023). Its CpG methylation site (cg08734237) strongly correlated with cognitive aging, suggesting an epigenetic regulatory role in neurological signaling and neurodegeneration (Mohammadnejad et al., 2021). These findings provide valuable insights into the molecular mechanisms of brain aging, highlighting the significant roles of ADAMTSL1, KCNA1, and KLHDC4 in microglial function and their associations with neurodegenerative processes. The identification of these genes underscores the importance of extracellular matrix remodeling, neuronal excitability regulation, and epigenetic modulation in aging and age-related diseases such as Alzheimer’s and Parkinson’s disease. Future research should validate these pathways in animal models and human studies, paving the way for targeted interventions to address cognitive decline and neurodegeneration in aging populations.