Constructing the denatured protein atlas map aimed at understanding individual aging and age-related diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19398
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Johmura Yoshikazu 金沢大学, がん進展制御研究所, 教授 (40616322)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 細胞老化 / 個体老化 / プロテオスタシス / 神経変性疾患

Outline of Final Research Achievements

Accumulation of denatured abnormal proteins due to proteostasis collapse is　undoubtedly one of the keys to individual aging and age-related disease onset. However, there are many uncertainties as to why proteostasis function declines with aging. Moreover, critically, comprehensive and integrated analyses regarding which proteins become denatured and abnormally accumulate during individual aging and age-related disease onset have not been conducted, except for　neurodegenerative diseases associated with certain genetic mutations.
In this study, by utilizing the unique protein characteristics that recognize a variety of denatured proteins of LONRF2 discovered by the applicants, we succeeded in identifying a group of denatured abnormal proteins that accumulate in individual aging and age-related diseases.

Free Research Field

老化生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、変性タンパク質を網羅的に同定するためのプラットフォームを構築することができたことにより、神経変性疾患を含めた加齢性関連疾患に関与する新しい原因遺伝子の同定につながる可能性も考えられる。また、将来的には構築したプラットフォームを基に作製する変性タンパク質アトラスマップと一細胞マウスアトラスなどの網羅的遺伝子発現データを組み合わせた機械学習などの生物計算学的解析により、各臓器・細胞種ごとの加齢に伴うプロテオスタシス破綻の遷移状態を描写することも可能となり、これまでにないプロテオスタシスを標的とした老化制御法の考案につながる。