Ischemic stroke is a well-recognized disease of aging, yet it is unclear how the age-dependent vulnerability occurs and what are the underlying mechanisms. To address these issues, we perform a comprehensive RNA-seq analysis of aging, ischemic stroke, and their interaction in 3- and 18-month-old mice. We assess differential gene expression across injury status and age, estimate cell type proportion changes, assay the results against a range of transcriptional signatures from the literature, and perform unsupervised co-expression analysis, identifying modules of genes with varying response to injury. We uncover downregulation of axonal and synaptic maintenance genetic program, and increased activation of type I interferon (IFN-I) signaling following stroke in aged mice. Together, these results paint a picture of ischemic stroke as a complex age-related disease and provide insights into interaction of aging and stroke on cellular and molecular level.

2nd Medical Faculty Charles University Prague Czech Republic

Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Vestec Czech Republic

Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Growth Regulators Faculty of Science Palacky University Olomouc Czech Republic

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$a Androvic, Peter $u Institute of Biotechnology of the Czech Academy of Sciences-BIOCEV, Vestec, Czech Republic; Laboratory of Growth Regulators, Faculty of Science, Palacky University, Olomouc, Czech Republic. Electronic address: peter.androvic@ibt.cas.cz

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$a Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain / $c P. Androvic, D. Kirdajova, J. Tureckova, D. Zucha, E. Rohlova, P. Abaffy, J. Kriska, M. Valny, M. Anderova, M. Kubista, L. Valihrach

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$a Ischemic stroke is a well-recognized disease of aging, yet it is unclear how the age-dependent vulnerability occurs and what are the underlying mechanisms. To address these issues, we perform a comprehensive RNA-seq analysis of aging, ischemic stroke, and their interaction in 3- and 18-month-old mice. We assess differential gene expression across injury status and age, estimate cell type proportion changes, assay the results against a range of transcriptional signatures from the literature, and perform unsupervised co-expression analysis, identifying modules of genes with varying response to injury. We uncover downregulation of axonal and synaptic maintenance genetic program, and increased activation of type I interferon (IFN-I) signaling following stroke in aged mice. Together, these results paint a picture of ischemic stroke as a complex age-related disease and provide insights into interaction of aging and stroke on cellular and molecular level.

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$a Kirdajova, Denisa $u Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Second Medical Faculty, Charles University, Prague, Czech Republic

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$a Tureckova, Jana $u Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic

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$a Zucha, Daniel $u Institute of Biotechnology of the Czech Academy of Sciences-BIOCEV, Vestec, Czech Republic

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$a Rohlova, Eva $u Institute of Biotechnology of the Czech Academy of Sciences-BIOCEV, Vestec, Czech Republic

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$a Abaffy, Pavel $u Institute of Biotechnology of the Czech Academy of Sciences-BIOCEV, Vestec, Czech Republic

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$a Kriska, Jan $u Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Second Medical Faculty, Charles University, Prague, Czech Republic

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$a Valny, Martin $u Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic

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$a Anderova, Miroslava $u Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic

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$a Kubista, Mikael $u Institute of Biotechnology of the Czech Academy of Sciences-BIOCEV, Vestec, Czech Republic

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$a Valihrach, Lukas $u Institute of Biotechnology of the Czech Academy of Sciences-BIOCEV, Vestec, Czech Republic. Electronic address: lukas.valihrach@ibt.cas.cz

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