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2023 Fiscal Year Final Research Report

Understanding of age-related muscle atrophy with impaired regeneration and its nutritional control

Research Project

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Project/Area Number 21H02347
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42010:Animal production science-related
Research InstitutionKyushu University

Principal Investigator

TATSUMI Ryuichi  九州大学, 農学研究院, 教授 (40250493)

Co-Investigator(Kenkyū-buntansha) 中島 崇  九州大学, 農学研究院, 助教 (20380553)
鈴木 貴弘  九州大学, 農学研究院, 准教授 (80750877)
前原 一満  九州大学, 生体防御医学研究所, 助教 (90726431)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywords骨格筋 / 筋幹細胞 / 活性化因子HGF / ニトロ化 / 加齢性筋萎縮・再生不全 / 健康かがく / 健康寿命 / 健康科学
Outline of Final Research Achievements

Myogenic stem satellite cell activator HGF (hepatocyte growth factor) contributes to postnatal muscle growth and regeneration after injury. We found that HGF is nitrated by incubation with peroxynitrite (ONOO-: a highly reactive biomolecule) to lose the biological activity in vitro. Here we show that with aging, extracellular HGF undergoes tyrosine-residue (Y) nitration and loses recepter c-met binding. Nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c-met-binding domains. Direct-immunofluorescence microscopy of rat lower hindlimb muscles, provided direct in vivo evidence for age-related increases in nitration of ECM-bound HGF in fast IIa, IIx myofibers. Overall, findings highlight inhibitory impacts of HGF nitration on myogenic stem cell dynamics, pioneering a cogent discussion for better understanding age-related muscle atrophy and impaired regeneration (including sarcopenia and frailty).

Free Research Field

筋細胞分子生理学、食肉科学、獣医学・畜産学

Academic Significance and Societal Importance of the Research Achievements

筋幹細胞が物理刺激を受容すると、HGFがECMから遊離し受容体c-metに結合することが活性化カスケードの重要な要素である。HGFがニトロ化しc-metに結合できなくなることは衛星細胞が活性化し増殖できないことを意味しており、その影響が加齢性筋萎縮や再生不全、筋幹細胞数の減少として徐々に進行・蓄積すると考えられる「細胞老化説」などに加えて新奇主要因と理解される一方、HGFのニトロ化・不活化だけで多くの加齢変化を明確に説明できることに本研究成果のインパクトがある。ニトロ化抑制活性を有する生体内分子や機能性食品成分を見出すことができれば、超高齢社会における「健康寿命」の延伸に貢献すると期待される。

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Published: 2025-01-30  

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