A physiologfical role of aging-associated suppression of mechanical sensor in sarcopenia

• Project/Area Number: 17K01762
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Sports science
• Research Institution: Hirosaki Gakuin University
• Principal Investigator: YOSHIOKA Toshitada 弘前学院大学, 看護学部, 学長 (50056933)
• Co-Investigator(Kenkyū-buntansha): 後藤 勝正 (山下勝正) 豊橋創造大学, 保健医療学部, 教授 (70239961)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 骨格筋 / 加齢性骨格筋萎縮 / 運動刺激 / 機械的刺激 / 遺伝子多様性 / 選択的スプライシング / MBNL1 / ミトコンドリア / アポトーシス / 加齢性筋萎縮 / 選択的スプライシング因子 / 加齢 / filamin C / 骨格筋萎縮

Outline of Final Research Achievements

The purpose of this study was to investigate a physiological role of mechanical sensor protein filamin C and a splicing factor muscleblind-like 1(MBNL1) in aging-associated skeletal muscle atrophy, so-called sarcopenia for development of skeletal muscle mass and function. Aging-associated skeletal muscle atrophy may be attributed to the depression of mechanical sensor filamin C of skeletal muscle cells. Further aging-associated down-regulation of MBNL1 may be a cause of sarcopenia via MBNL1-mitochondria-apoptosis axis. Therefore, aging may suppress the sensitivity of skeletal muscle cells for exercise-associated stimuli.

Academic Significance and Societal Importance of the Research Achievements

骨格筋機能の低下は、高齢者の転倒リスクを増加させることは疑いの余地はない。超高齢社会に突入した我が国では、加齢性骨格筋萎縮（サルコペニア）による運動機能低下の予防策および治療法の確立は喫緊の課題である。加齢による骨格筋の萎縮は運動刺激に対する感受性の低下を伴っていることから、運動刺激の強度や刺激入力頻度あるいは刺激の種類を工夫することで、加齢性の骨格筋委縮は抑制できるかもしれない。高齢者に対する運動強度や頻度増加は困難である場合が多いことから、運動刺激の種類を工夫することが重要と考えられる。一方で、運動刺激に対する感受性の維持・向上策の開発も望まれる。

Research Products

• [Int'l Joint Research] King's College London(英国)
• [Journal Article] 筋トレの生化学：筋肥大のメカニズム (2020)
  • Author(s): 後藤勝正
  • Journal Title: 臨床リハビリテーション Volume: 29 Pages: 116-122
• [Journal Article] Lactate stimulates a potential for hypertrophy and regeneration of mouse skeletal muscle (2019)
  • Author(s): Ohno Y, Ando K, Ito T, Suda Y, Matsui Y, Oyama A, Kaneko H, Yokoyama S, Egawa T, Goto K.
  • Journal Title: Nutrients Volume: 11 Issue: 4 Pages: 869-869
  • DOI: 10.3390/nu11040869
  • Peer Reviewed / Open Access
• [Journal Article] MENS-associated increase of muscular protein content via modulation of caveolin-3 and TRIM72 (2019)
  • Author(s): Ohno Y, Egawa T, Yokoyama S, Fujiya H, Sugiura T, Ohira Y, Yoshioka T, Goto K.
  • Journal Title: Physiological Research Volume: 68 Pages: 265-273
  • DOI: 10.33549/physiolres.933992
  • Peer Reviewed / Open Access
• [Journal Article] Impact of different temperature stimuli on the expression of myosin heavy chain isoforms during recovery from bupivacaine-induced muscle injury in rats (2019)
  • Author(s): Shibaguchi, T., Hoshi, M., Yoshihara, T., Naito, H., Goto, K., Yoshioka, T., Sugiura, T.
  • Journal Title: Journal of Applied Physiology Volume: 127 Issue: 1 Pages: 178-189
  • DOI: 10.1152/japplphysiol.00930.2018
  • Peer Reviewed
• [Journal Article] The Protective Effect of Brazilian Propolis against Glycation Stress in Mouse Skeletal Muscle (2019)
  • Author(s): Egawa T, Ohno Y, Yokoyama S, Yokokawa T, Tsuda S, Goto K, Hayashi T.
  • Journal Title: Foods Volume: 8 Issue: 10 Pages: 439-439
  • DOI: 10.3390/foods8100439
  • NAID: 120006766120
  • Peer Reviewed / Open Access
• [Journal Article] 宇宙医学研究からロコモティブシンドロームを解明する (2019)
  • Author(s): 後藤勝正
  • Journal Title: 整形災害外科 Volume: 62 Pages: 763-770
• [Journal Article] Age-related changes in myostatin expression in rat skeletal muscles (2018)
  • Author(s): Shibaguchi Tsubasa、Maeoka Takeshi、Yoshihara Toshinori、Naito Hisashi、Goto Katsumasa、Yoshioka Toshitada、Sugiura Takao
  • Journal Title: The Journal of Physical Fitness and Sports Medicine Volume: 7 Issue: 4 Pages: 221-227
  • DOI: 10.7600/jpfsm.7.221
  • NAID: 130007406080
  • ISSN: 2186-8123, 2186-8131
  • Year and Date: 2018-07-25
  • Peer Reviewed / Open Access
• [Journal Article] The effect of advanced glycation end products on cellular signaling molecules in skeletal muscle (2018)
  • Author(s): Egawa Tatsuro、Ohno Yoshitaka、Yokoyama Shingo、Goto Ayumi、Ito Rika、Hayashi Tatsuya、Goto Katsumasa
  • Journal Title: The Journal of Physical Fitness and Sports Medicine Volume: 7 Issue: 4 Pages: 229-238
  • DOI: 10.7600/jpfsm.7.229
  • NAID: 130007406072
  • ISSN: 2186-8123, 2186-8131
  • Year and Date: 2018-07-25
  • Peer Reviewed / Open Access
• [Journal Article] Lactate increases myotube diameter via activation of MEK/ERK pathway in C2C12 cells (2018)
  • Author(s): Ohno Y.、Oyama A.、Kaneko H.、Egawa T.、Yokoyama S.、Sugiura T.、Ohira Y.、Yoshioka T.、Goto K.
  • Journal Title: Acta Physiologica Volume: 223 Issue: 2
  • DOI: 10.1111/apha.13042
  • Peer Reviewed
• [Journal Article] AMPK Mediates Muscle Mass Change But Not the Transition of Myosin Heavy Chain Isoforms during Unloading and Reloading of Skeletal Muscles in Mice (2018)
  • Author(s): Egawa Tatsuro、Ohno Yoshitaka、Goto Ayumi、Yokoyama Shingo、Hayashi Tatsuya、Goto Katsumasa
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 10 Pages: 2954-2954
  • DOI: 10.3390/ijms19102954
  • NAID: 120006534581
  • Peer Reviewed / Open Access
• [Journal Article] Activation of adiponectin receptors has negative impact on muscle mass in C2C12 myotubes and fast-type mouse skeletal muscle (2018)
  • Author(s): Ito Rika、Higa Masaki、Goto Ayumi、Aoshima Megumi、Ikuta Akihiro、Ohashi Kazuya、Yokoyama Shingo、Ohno Yoshitaka、Egawa Tatsuro、Miyata Hirofumi、Goto Katsumasa
  • Journal Title: PLOS ONE Volume: 13 Issue: 10 Pages: 0205645-0205645
  • DOI: 10.1371/journal.pone.0205645
  • NAID: 120006559414
  • Peer Reviewed / Open Access
• [Journal Article] Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy (2018)
  • Author(s): Toshinori Yoshihara, Takao Sugiura, Nobuyuki Miyaji, Yuki Yamamoto, Tsubasa Shibaguchi, Ryo Kakigi, Hisashi Naito, Katsumasa Goto, Daijiro Ohmori, Toshitada Yoshioka
  • Journal Title: Journal of Zhejiang University SCIENCE B Volume: N/A Issue: 11 Pages: 844-852
  • DOI: 10.1631/jzus.b1800076
  • Peer Reviewed / Open Access
• [Journal Article] Nuclear Accumulation of HSP70 in Mouse Skeletal Muscles in Response to Heat Stress, Aging, and Unloading With or Without Reloading (2018)
  • Author(s): Apostolopoulos Antonios、Nakamura Ayane、Yokoyama Shingo、Aoshima Megumi、Fujimoto Risa、Nakamura Kodai、Ito Rika、Goto Katsumasa
  • Journal Title: Frontiers in Genetics Volume: 9 Pages: 617-617
  • DOI: 10.3389/fgene.2018.00617
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 筋力および筋力低下の生理学 (2018)
  • Author(s): 後藤勝正，吉岡利忠
  • Journal Title: 理学療法ジャーナル Volume: 52 Pages: 5-14
• [Presentation] A possible of gastric inhibitory polypeptide in the regulation of skeletal muscle mass (2020)
  • Author(s): Goto, K., Aoshima, M., Hagiwara, A., Yamashita, T., Ortuste Quiroga, H.P., Yokoyama, S.
  • Organizer: 第97回日本生理学会大会
• [Presentation] A physiological role of inter-organ network between gastrointestine and skeletal muscle on the regulation of skeletal muscle volume (2019)
  • Author(s): Goto, K., Aoshima, M., Suzuki, T., Kanda, Y., Inagaki, R., Akiyama, K., Yokoyama, S.
  • Organizer: Experimental Biology 2019 (EB2019)
  • Int'l Joint Research
• [Presentation] 持続的なTRPV4チャネルの活性化と不活性化による筋管細胞の適応 (2019)
  • Author(s): 萩原ありさ，山下智大，Ortuste Quiroga, H.P.，伊藤理香，大野善隆，横山真吾，後藤勝正
  • Organizer: 第74回日本体力医学会大会
• [Presentation] 筋細胞の分化におけるHSP70特異的核輸送体Hikeshiの役割 (2019)
  • Author(s): 山下智大，Ortuste Quiroga, H.P.，萩原ありさ，横山真吾，大野善隆，杉浦崇夫，大平充宣，吉岡利忠，後藤勝正
  • Organizer: 第74回日本体力医学会大会
• [Presentation] Some aspects of mechanosensitive ion channels in myogenesis (2019)
  • Author(s): Ortuste Quiroga, H.P., Yamashita, Y., Hagiwara, A., Yokoyama, S., Suzuki, Y., Tominaga, M., Goto, K.
  • Organizer: 第74回日本体力医学会大会
• [Presentation] 長期間の機能的過負荷による筋サテライト細胞と筋タンパク合成シグナルの変化 (2019)
  • Author(s): 杉浦崇夫，森廣壮馬，芝口翼，内藤久士，後藤勝正，吉岡利忠
  • Organizer: 第74回日本体力医学会大会
• [Presentation] Functional properties of a novel mechanosensitive Ca2+-permeable channel in mouse muscle satellite cells (2019)
  • Author(s): Ortuste Quiroga, H.P., Yamashita, T., Hagiwara, A., Yokoyama, S., Suzuki, Y., Tominaga, M., Goto, K.
  • Organizer: Frontiers in Myogenesis, Skeletal Muscle: Development, Regeneration and Disease
  • Int'l Joint Research
• [Presentation] HSP70-specific nuclear transporter Hikeshi in myogenic differentiation (2019)
  • Author(s): Yamashita, T., Ortuste Quiroga, H.P., Hagiwara, A., Yokoyama, S., Ohno, Y., Sugiura, T., Ohira, Y., Yoshioka, T., Goto, K.
  • Organizer: Frontiers in Myogenesis, Skeletal Muscle: Development, Regeneration and Disease
  • Int'l Joint Research
• [Presentation] 骨格筋細胞可塑性発現におけるTRPV4と機械的刺激の受容 (2019)
  • Author(s): 萩原ありさ，大野善隆，横山真吾，後藤勝正
  • Organizer: 第65回日本宇宙航空環境医学会大会
• [Presentation] Adiponectin and skeletal muscle - new insights and potential implications (2019)
  • Author(s): Goto, K.
  • Organizer: The 9th FAOPS (Federation of the Asian and Oceanian Physiological Societies) Congress, The 96th Annual Meeting of the Physiological Society of Japan
  • Int'l Joint Research / Invited
• [Presentation] A possible role in linear ubiquitin assembly complex in skeletal muscle cells (2018)
  • Author(s): Goto, K., Nakamura, K., Yokoyama, S.
  • Organizer: Muscle development, regeneration and disease 2018
  • Int'l Joint Research
• [Presentation] Nuclear accumulation of HSP70 protein in mouse skeletal muscles in response to reloading following unloading (2018)
  • Author(s): Goto, K., Apostolopoulus, A., Nakamura, A., Ohira, Y.
  • Organizer: The Life Sciences Meeting 2018, The Symposium combines the 39th Annual International Gravitational Physiology (ISGP) Meeting and the ESA Space meets Health initiative
  • Int'l Joint Research
• [Presentation] A physiological role of gastric inhibitory polypeptide receptor in myogenic differentiation of C2C12 myoblasts (2018)
  • Author(s): Goto, K., Aoshima, M., Suzuki, T., Kanda, Y., Inagaki, R., Akiyama, K., Yokoyama, S.
  • Organizer: 2018 FASEB SRC (Federation of American Societies for Experimental Biology, Science Research Conferences) “Skeletal Muscle Satellite Cells and Regeneration”
  • Int'l Joint Research
• [Presentation] 長期間の抗酸化食摂取と機能的過負荷が筋肥大に及ぼす影響 (2018)
  • Author(s): 杉浦崇夫，芝口翼，宮司進之，内藤久士，後藤勝正，吉岡利忠
  • Organizer: 第73回日本体力医学会大会
• [Presentation] 哺乳類骨格筋細胞におけるHikeshiタンパク質の発現 (2018)
  • Author(s): 山下智大，Huascar Pedro Ortuste Quiroga ，中村晃大，藤本理沙，伊藤理香，横山真吾，大野善隆，大橋和也，杉浦崇夫，大平充宣，吉 岡利忠，後藤勝正
  • Organizer: 第73回日本体力医学会大会
• [Presentation] 哺乳類骨格筋細胞の分化におけるHSF2およびHSF4の役割 (2018)
  • Author(s): 藤本理沙，中村晃大，山下智大，Huascar Pedro Ortuste Quiroga，伊藤理香，横山真吾，大野善隆，大橋和也，杉浦崇夫，大平充宣，吉 岡利忠，後藤勝正
  • Organizer: 第73回日本体力医学会大会
• [Presentation] 培養骨格筋細胞の増殖と分化における直鎖状ユビキチン鎖リガーゼ複合体LUBACの機能 (2018)
  • Author(s): 中村晃大，藤本理沙，Huascar Pedro Ortuste Quiroga，山下智大，伊藤理香，横山真吾，大野善隆，大橋和也，杉浦崇夫，大平充宣，吉 岡利忠，後藤勝正
  • Organizer: 第73回日本体力医学会大会
• [Presentation] Knockdown of HOIL-1L suppresses proliferation and differentiation of C2C12 myoblasts (2018)
  • Author(s): Nakamura, K., Fujimoto, R., Huascar Pedro Ortuste Quiroga1, Yamashita, T , Ito, R., Yokoyama, S., Ohno, Y., Sugiura, T., Ohira, Y., Yoshioka, T. Goto, K.
  • Organizer: The 34th Annual Meeting of the American Society for Gravitational and Space Research (ASGSR)
  • Int'l Joint Research
• [Presentation] Possible role of heat shock transcription factor 4 in differentiation of skeletal muscle cells (2018)
  • Author(s): Fujimoto, R., Nakamura, K., Yamashita, T., Huascar Pedro Ortuste Quiroga1, Ito, R., Yokoyama, S., Ohno, Y., Ohashi, K., Sugiura, T., Ohira, Y., Yoshioka, T. Goto, K.
  • Organizer: The 34th Annual Meeting of the American Society for Gravitational and Space Research (ASGSR)
  • Int'l Joint Research
• [Presentation] 温熱刺激に対する骨格筋の応答とその生理学的意義 (2018)
  • Author(s): 後藤勝正
  • Organizer: 第64回日本宇宙航空環境医学会大会，シンポジウム「抗重力筋活動レベルが筋の発育・発達、萎縮、肥大に及ぼす影響」
  • Invited
• [Presentation] 宇宙医学研究のスピンオフ－健康長寿社会を支える宇宙医学研究の視点－ (2018)
  • Author(s): 後藤勝正
  • Organizer: 第8回日本航空宇宙精神神経学会
  • Invited
• [Presentation] 非荷重空間における筋肉の減少 (2018)
  • Author(s): 後藤勝正
  • Organizer: 第3回日本抗加齢協会フォーラム，テーマ：春・夏・秋・冬のアンチエイジング
  • Invited
• [Presentation] MBNL1-associated mitochondrial dysfunction and apoptosis in C2C12 myotubes and mouse skeletal muscle (2018)
  • Author(s): Yokoyama, S., Ohno, Y., Egawa, T., Nakamura, A., Goto, K.
  • Organizer: International Conference on Frailty & Sarcopenia Research 2019 (ICFSR 2019)
  • Int'l Joint Research
• [Presentation] 哺乳類骨格筋細胞における機械的刺激受容Ca2+チャネルについての一考察 (2018)
  • Author(s): 後藤勝正
  • Organizer: 第6回骨格筋生物学研究会
• [Presentation] A possible role of skeletal muscle-derived adiponectin in the regulation of skeletal muscle mass (2017)
  • Author(s): Goto, K., Ito, R., Higa, M., Yokoyama, S., Sugiura, T., Miyata, H., Ohira, Y., Yoshioka, T
  • Organizer: Experimental Biology 2017
  • Int'l Joint Research
• [Presentation] 加齢による骨格筋組織内蓄積脂肪の増加－マウスヒラメ筋を用いた検討－ (2017)
  • Author(s): 横山真吾，大野善隆，池谷直美，中村文音，比嘉正輝，青島恵，後藤勝正
  • Organizer: 第52回日本理学療法学術大会
• [Presentation] カフェ酸およびクロロゲン酸が骨格筋細胞の分化に与える影響 (2017)
  • Author(s): 横山真吾，江川達郎，大野善隆，後藤勝正
  • Organizer: 第71回日本栄養・食量学会大会
• [Presentation] 骨格筋細胞における直鎖状ユビキチン鎖リガーゼ複合体LUBACの発現 (2017)
  • Author(s): 中村晃大，藤本理沙，青島恵，伊藤理香，横山真吾，大野善隆，大橋和也，杉浦崇夫，大平充宣，吉岡利忠，後藤勝正
  • Organizer: 第72回日本体力医学会大会
• [Presentation] 骨格筋細胞の分化に伴う熱ショック転写因子の発現応答 (2017)
  • Author(s): 藤本理沙，中村晃大，青島恵，伊藤理香，横山真吾，大野善隆，大橋和也，杉浦崇夫，大平充宣，吉岡利忠，後藤勝正
  • Organizer: 第72回日本体力医学会大会
• [Presentation] グルコース依存性インスリン分泌刺激ポリペプチド受容体のノックダウンが骨格筋細胞の分化に及ぼす影響 (2017)
  • Author(s): 青島恵，伊藤理香，藤本理沙，中村晃大，大橋和也，横山真吾，大野善隆，杉浦崇夫，大平充宣，吉岡利忠，朝倉淳，後藤勝正
  • Organizer: 第72回日本体力医学会大会
• [Presentation] 骨格筋萎縮に伴う選択的スプライシング因子の挙動 (2017)
  • Author(s): 中村文音，大野善隆，横山真吾，伊藤理香，比嘉正輝，青島恵，杉浦崇夫，大平充宣，吉岡利忠，後藤勝正
  • Organizer: 第72回日本体力医学会大会
• [Presentation] マウス骨格筋におけるPGC-1a発現の加齢性低下とMBNL1の関与 (2017)
  • Author(s): 横山真吾，大野善隆，江川達郎，中村文音，後藤勝正
  • Organizer: 第72回日本体力医学会大会
• [Presentation] Some aspects of HSF2 and HSF4 in differentiation of skeletal muscle cells (2017)
  • Author(s): Fujimoto, R, Nakamura, K., Aoshima, M., Ito, R., Yokoyama, S., Sugiura, T., Ohira, Y., Yoshioka, T., Goto, K.
  • Organizer: 2017 Annual Meeting of American Society for Gravitational and Space Research (ASGSR)
  • Int'l Joint Research
• [Presentation] Profiles of linear ubiquitin assembly complex in skeletal muscle (2017)
  • Author(s): Nakamura, K., Fujimoto, R, Aoshima, M., Ito, R., Yokoyama, S., Ohno, Y., Ohashi, K., Sugiura, T., Ohira, Y., Yoshioka, T., Goto, K.
  • Organizer: 2017 Annual Meeting of American Society for Gravitational and Space Research (ASGSR)
  • Int'l Joint Research
• [Presentation] Ageing-associated nuclear accumulation HSP70 of mouse skeletal muscles (2017)
  • Author(s): Apostolopoulos, A., Nakamura, A., Russomano, T., Green, D.A., Goto, K.
  • Organizer: Biology of Ageing II “Impactful Intervenstions” Systems - Models - Pathways - Diseases
  • Int'l Joint Research
• [Presentation] 荷重除去による骨格筋萎縮とその後の再成長に伴う筋核内ストレスタンパク質の変化 (2017)
  • Author(s): 後藤勝正
  • Organizer: 第63回日本宇宙航空環境医学会大会