中外創薬 助成研究報告書2023
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大阪公立大学大学院医学研究科病態生理学Department of Pathophysiology, Osaka Metropolitan University Graduate School of Medicine― 127 ―Although regulatory mechanisms of proteostasis have been implicated in aging, it is still unclear to what extent and how post-transcriptional dysregulation affects aging proteome. Thus, we performed quantitative proteomic analysis of whole-tissue lysates and low-solubility protein-enriched fractions (LSF) of major tissues collected from 6, 15, 24, and 30 months old mice, and analyzed these data in combination with transcriptomic data collected from the same mouse tissue samples. We found in all investigated tissues that extracellular matrix (ECM) proteins were overrepresented in proteins that were increased during aging. Age-related changes in ECM proteins tended not to be accompanied by significant changes in mRNA levels, suggesting the role of post-transcriptional regulation. ECM proteins that increased during aging were highly tissue-dependent, but a fraction of proteins that may promote extracellular protein deposition, such as ApoE, HTRA1, and THBS1, were increased in the majority of tissues. Abstractはじめに高齢化は⽇本を含む世界の先進国における主要な社会問題の一つである.この問題を解決する重要なアプローチの一つとして,大部分の加齢性疾患において根本的な発症要因の一つとなっている老化そのもののメカニズムを解明し,それに干渉する事で寿命と健康寿命のギャップを埋めていく事が目指されている.その実現に向けて,まずは加齢に伴う分子レベルの変化を包括的かつ定量的に記述し,老化の理解を立脚させるための情報基盤を築く事が重要となってくる.この点に関して,これまでマAging proteomic atlasを構築し老化のメカニズムをConstruction of mouse aging proteomic atlas and clarification of the features of age-related post-transcriptional タンパクレベルから明らかにするdysregulation高杉 征樹Masaki Takasugi

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