Department of Neuroscience of Disease, Brain Research Institute, Niigata UniversityAbstractはじめに近年，核の障害などが原因で核DNA が細胞質に漏出した場合に，cGAS-STING経路がそれを認識し，炎症反応や細胞老化関連分泌形質（SASP）を惹起し，個体老化につながることが報告されている1, 2)．また申請者はミトコンドリアDNAの漏出がIFI16を介して様々な細胞応答と疾患病理を惹起することを報告した3)．このような言わば異所性の核DNAやミトコンドリアDNAはSASPを介して，周囲の細胞や組織あるいは遠隔にも老化・炎症・癌化を誘導する可能性が示唆されている．しかし個体におけるそれらの臓器連関に関してはほとんどわかっていない．本研究ではモデル動物において異所性の核DNA，異所性のミトコンドリアDNAが惹起する近隣や遠隔への臓器連関をin vivoで検証する．それらにより老化や加齢関連疾患の，個々の特徴的な局所の病理と臓器連関を明らかにする．並行して細胞外液に含まれるタンパク質やDNAの解析手法を樹立し，異所性の核DNAやミトコン新潟大学脳研究所脳病態解析分野― 85 ―In recent years, it has been reported that nuclear DNA leakage into the cytoplasm due to nuclear damage triggers the recognition of this DNA by the cGAS-STING pathway, resulting in inflammatory reactions and the induction of cellular senescence-related secretory phenotype (SASP), ultimately contributing to organismal aging. Additionally, the leakage of mitochondrial DNA has been implicated in various cellular responses and disease pathologies. This study aims to validate organ interactions, both local and distant, induced by ectopic nuclear and mitochondrial DNA in model animals in vivo. We seek to elucidate the distinctive local pathologies and organ interactions associated with aging and age-related diseases. Simultaneously, we will establish analytical techniques for proteins and DNA in the extracellular fluid to analyze extracellular responses induced by ectopic nuclear or mitochondrial DNA, including SASP, as well as extracellular responses induced in conditions of aging and age-related diseases, revealing their impacts on these diseases. 松井 秀彰Hideaki MatsuiOrgan…Network…of…Aging…and…Age-Related…Diseases老化と加齢関連疾患の臓器連関
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