Sex differences in skeletal muscle stem cells

• Project/Area Number: 16H03205
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Juntendo University
• Principal Investigator: Machida Shuichi 順天堂大学, スポーツ健康科学研究科, 教授 (40421226)
• Co-Investigator(Kenkyū-buntansha): 岡本 武志 東海大学, 健康学部, 講師 (80638320)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
• Keywords: 筋サテライト細胞 / 筋分化 / 性差 / エピジェネティクス / 筋分化能 / サルコペニア / 骨格筋幹細胞 / エピジェネティック / 精査

Outline of Final Research Achievements

Aging is associated with sarcopenia, which is defined by reductions in skeletal muscle mass, strength, and physical function. Sarcopenia decreases the ability to perform activities of daily living, reduces quality of life, and increases fall-risk and associated injuries. Older women exhibit greater frailty and skeletal muscle mass and strength losses compared to that in older men. It is likely that the underlying causes of sarcopenia are different in women and men, which will require the identification of sex-specific therapeutic targets.
Skeletal muscles are generally considered to have high regenerative capacity. However, muscle regeneration capacity progressively declines with aging. Satellite cells are a group of adult muscle stem cells that play a key role in mediating muscle regeneration. Recent studies have shown that satellite cells progressively undergo sex-specific changes in cell-intrinsic characteristics and functions.

Academic Significance and Societal Importance of the Research Achievements

サルコペニア発症の要因のひとつとして、怪我等による筋損傷からの再生が補いきれないために顕在化するという考えがある。特に、女性においては、性ホルモンのエストロゲン分泌が低下した閉経以降では顕著に筋再生能が失われる。本研究では、骨格筋幹細胞である筋サテライト細胞の筋分化能には性差が認められ、エストロゲンの影響を受けることを示唆した。骨格筋の幹細胞に関するこれまでの知見は、株化された筋芽細胞から得られた結果より推察されたことが多く見受けられた。しかし、本研究のように、性差の影響を細胞レベルで明らかにすることで、性別に応じたサルコペニア予防の介入方法を開発する上での有益な基礎資料になると思われる。

Research Products

• [Int'l Joint Research] University of Physical Education(Hungary)
• [Journal Article] Differential protective effects of <i>Radix astragali</i>, herbal medicine, on immobilization-induced atrophy of slow-twitch and fast-twitch muscles (2020)
  • Author(s): Nozaki R, Hung Y-L, Takagi K, Nakano D, Fujii T, Kawanishi N, Okamoto T, Machida S.
  • Journal Title: Biomedical Research Volume: 41 Issue: 3 Pages: 139-148
  • DOI: 10.2220/biomedres.41.139
  • NAID: 130007853776
  • ISSN: 0388-6107, 1880-313X
  • Year and Date: 2020-06-01
  • Peer Reviewed / Open Access
• [Journal Article] Can Blood Parameters Predict the Risk of Locomotive Syndrome in MiddleAged and Older Individuals? A Literature Review (2020)
  • Author(s): Toshinori Yoshihara, Shuichi Machida, Hisashi Naito
  • Journal Title: International Journal of Physical Medicine and Rehabilitation Volume: 8 Pages: 546-546
  • Peer Reviewed
• [Journal Article] Age-related changes in histone modification in rat gastrocnemius muscle. (2019)
  • Author(s): Yoshihara T, Machida S, Tsuzuki T, Kakigi R, Chang SW, Sugiura T, Naito H.
  • Journal Title: Exp Gerontol. Volume: 125 Pages: 110658-110658
  • DOI: 10.1016/j.exger.2019.110658
  • Peer Reviewed
• [Journal Article] Vitamin C deficiency causes muscle atrophy and a deterioration in physical performance. (2019)
  • Author(s): Takizawa, S., Funakoshi, T., Yatsu, T., Nagata, K., Aigaki, T., Machida, S., and Ishigami. A
  • Journal Title: Sci. Rep. Volume: 9 Issue: 1 Pages: 4702-4702
  • DOI: 10.1038/s41598-019-41229-7
  • NAID: 130007919173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association between Locomotive Syndrome and blood parameters in Japanese middle-aged and elderly individuals: A cross-sectional study. (2019)
  • Author(s): Yoshihara T, Ozaki H, Nakagata T, Natsume T, Kitada T, Ishihara Y, Sawada S, Ishibashi M, Kobayashi H, Machida S, Naito H.
  • Journal Title: BMC Musculoskelet Disord. Volume: 20 Issue: 1 Pages: 104-104
  • DOI: 10.1186/s12891-019-2480-9
  • Peer Reviewed / Open Access
• [Journal Article] Effects of Progressive Walking and Stair-Climbing Training Program on Muscle Size and Strength of the Lower Body in Untrained Older Adults. (2019)
  • Author(s): Ozaki H, Nakagata T, Yoshihara T, Kitada T, Natsume T, Ishihara Y, Deng PY, Kobayashi H, Machida S, Naito H.
  • Journal Title: J Sports Sci Med. Volume: 18 Pages: 722-728
  • Peer Reviewed
• [Journal Article] A nationwide observational study of locomotive syndrome in Japan using the ResearchKit: The Locomonitor study (2019)
  • Author(s): Yoshimura Yusuke、Ishijima Muneaki、Ishibashi Masayoshi、Liu Liz、Arikawa-Hirasawa Eri、Machida Shuichi、Naito Hisashi、Hamada Chieko、Kominami Eiki
  • Journal Title: Journal of Orthopaedic Science Volume: 24 Issue: 6 Pages: 1094-1104
  • DOI: 10.1016/j.jos.2019.08.009
  • Peer Reviewed / Open Access
• [Journal Article] Endurance exercise training and high-fat diet differentially affect composition of diacylglycerol molecular species in rat skeletal muscle (2018)
  • Author(s): Kawanishi Noriaki、Takagi Kana、Lee Hyeon-Cheol、Nakano Daiki、Okuno Toshiaki、Yokomizo Takehiko、Machida Shuichi
  • Journal Title: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Volume: 印刷中 Issue: 6 Pages: R892-R901
  • DOI: 10.1152/ajpregu.00371.2017
  • Peer Reviewed / Open Access
• [Journal Article] Time-course study of macrophage infiltration and inflammation in cast immobilization?induced atrophied muscle of mice (2018)
  • Author(s): Kawanishi N、Funakoshi T、Machida S.
  • Journal Title: Muscle & Nerve Volume: 57 Issue: 6 Pages: 1006-1013
  • DOI: 10.1002/mus.26061
  • Peer Reviewed
• [Journal Article] Quercetin inhibits adipogenesis of muscle progenitor cells in vitro (2018)
  • Author(s): Funakoshi T、Kanzaki N、Otsuka Y、Izumo Ti、Shibata H、Machida S.
  • Journal Title: Biochemistry and Biophysics Reports Volume: 13 Pages: 39-44
  • DOI: 10.1016/j.bbrep.2017.12.003
  • Peer Reviewed / Open Access
• [Journal Article] Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration (2018)
  • Author(s): Hatazawa Yukino、Ono Yusuke、Hirose Yuma、Kanai Sayaka、Fujii Nobuharu L.、Machida Shuichi、Nishino Ichizo、Shimizu Takahiko、Okano Masaki、Kamei Yasutomi、Ogawa Yoshihiro
  • Journal Title: The FASEB Journal Volume: 32 Issue: 3 Pages: 1452-1467
  • DOI: 10.1096/fj.201700573r
  • Peer Reviewed / Open Access
• [Journal Article] <b>Changes in FOXO and proinflammatory cytokines in the late stage of immobilized fast and slow muscle atr</b><b>ophy </b> (2017)
  • Author(s): Okamoto T, Machida S
  • Journal Title: Biomedical Research Volume: 38 Issue: 6 Pages: 331-342
  • DOI: 10.2220/biomedres.38.331
  • NAID: 130006248348
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed
• [Journal Article] TLR4 defective (C3H/HeJ) mice are not protected from cast immobilization induced muscle atrophy (2017)
  • Author(s): Kawanishi N, Nozaki R, Naito H, Machida S
  • Journal Title: Physiological Reports Volume: 5 Issue: 8 Pages: e13255-e13255
  • DOI: 10.14814/phy2.13255
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SIRT1 may play a crucial role in overload induced hypertrophy of skeletal muscle (2017)
  • Author(s): Koltai E, Bori Z, Chabert C, Dubouchaud H, Naito H, Machida S, Davies KJ, Murlasits Z, Fry AC, Boldogh I, Radak Z
  • Journal Title: The Journal of physiology Volume: 印刷中 Issue: 11 Pages: 3361-3376
  • DOI: 10.1113/jp273774
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circadian rhythm of intracellular protein synthesis signaling in rat cardiac and skeletal muscles (2017)
  • Author(s): Chang SW, Yoshihara T, Machida S, Naito H
  • Journal Title: Biochemistry and Biophysics Reports Volume: 9 Pages: 153-158
  • Peer Reviewed / Open Access
• [Journal Article] The G allele of the IGF2 ApaI polymorphism is associated with judo status (2016)
  • Author(s): Itaka T, Agemizu K, Aruga S, Machida S
  • Journal Title: J Strength Cond Res Volume: 30 Issue: 7 Pages: 2043-2048
  • DOI: 10.1519/jsc.0000000000001300
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] The effect of Loquat Leaves Extract administration and electromyostimulated exercise on muscle protein synthesis signaling. (2020)
  • Author(s): Riki Kosugi, Yung-Li Hung, Toshiharu Natsume, Shuichi Machida.
  • Organizer: International Conference on Frailty and Sarcopenia Research 2020
  • Int'l Joint Research
• [Presentation] Low pre-training serum albumin level might restrict the effect of low-load resistance training on muscle thickness. (2020)
  • Author(s): Shuji Sawada, Hayao Ozaki, Toshiharu Natsume, Daiki Nakano, Pengyu Deng, Toshinori Yoshihara, Takuya Osawa, Shuichi Machida, Hisashi Naito
  • Organizer: Conference on Frailty and Sarcopenia Research 2020
  • Int'l Joint Research
• [Presentation] Sex difference in sarcopenia: mechanisms and interventions. (2019)
  • Author(s): Shuichi Machida
  • Organizer: 9th Federation of the Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research / Invited
• [Presentation] Estrogen deficiency leads to decreased water channel aquaporin 4 expression in skeletal muscle. (2019)
  • Author(s): Hung YL, Ota K, Ishido M, Machida S
  • Organizer: 9th Federation of the Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research
• [Presentation] サルコペニアにおける性差： メカニズムと運動介入の効果 (2019)
  • Author(s): 町田修一
  • Organizer: 第38回日本臨床運動療法学会
  • Invited
• [Presentation] サルコペニアに伴う骨格筋内脂肪蓄積のメカニズム (2019)
  • Author(s): 町田修一
  • Organizer: 第6回日本サルコペニア・フレイル学会大会
  • Invited
• [Presentation] 筋力アップで延ばす健康寿命 ～持続可能な活力ある社会構築を目指して～ (2019)
  • Author(s): 町田修一
  • Organizer: 第53回日本成人病（生活習慣病）学会学術集会
  • Invited
• [Presentation] サルコペニア予防のための運動プログラムに骨格筋の性差は考慮されるべきか？ (2017)
  • Author(s): 町田修一
  • Organizer: 第72回日本体力医学会大会シンポジウム
  • Invited
• [Presentation] サルコペニアを細胞生物学的に理解するヒント －筋線維と筋サテライト細胞に着目して－ (2017)
  • Author(s): 町田修一
  • Organizer: 第4回サルコペニア・フレイル学会大会シンポジウム
  • Invited
• [Presentation] Estradiol changes mitochondrial morphology into complexity in response to exercise (2017)
  • Author(s): Nakano D, Machida S
  • Organizer: Experimental Biology 2017
  • Int'l Joint Research
• [Presentation] Mitochondrial morphological changes differ between skeletal muscle types and in the different phases of the menstrual cycle in response to acute exercise (2017)
  • Author(s): Nakano D, Machida S
  • Organizer: Cell Symposia: Exercise Metabolism
  • Int'l Joint Research
• [Presentation] Vitamin C deficiency in skeletal muscle switches muscle fiber types from slow to fast (2017)
  • Author(s): Kondo Y, Takisawa S, Noda Y, Machida S, Aigaki T, Ishigami A
  • Organizer: The International Conference on Frailty & Sarcopenia Research 2017
  • Int'l Joint Research
• [Presentation] 高齢期における骨格筋の性差 (2016)
  • Author(s): 町田修一
  • Organizer: 第3回日本サルコペニア・フレイル研究会研究発表会ワークショップ
  • Place of Presentation: 名古屋
  • Year and Date: 2016-11-06
  • Invited
• [Presentation] Effects of acute aerobic exercise on mitochondrial morphology in endurance-trained rats (2016)
  • Author(s): Nakano D, Takagi K, Machida S
  • Organizer: 2016 APS Intersociety Meeting: The Integrative Biology of Exercise VII
  • Place of Presentation: Arizona, USA
  • Year and Date: 2016-11-02
  • Int'l Joint Research
• [Presentation] Physical inactivity-induced histone modification in rat soleus muscle (2016)
  • Author(s): Yoshihara T, Kakigi R, Tsuzuki T, Shuo-wen C, Natsume T, Takamine Y, Ichinoseki-Sekine N, Machida S, Sugiura T, Naito H
  • Organizer: American College of Sports Medicine 63th Annual Meeting
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2016-05-31
  • Int'l Joint Research