Mechanisms underlying the effect of calorie restriction : Analyses of neuropeptide Y and receptor subtypes

• Project/Area Number: 19590227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Nagasaki University
• Principal Investigator: SHIMOKAWA Isao Nagasaki University, 大学院・医歯薬学総合研究科, 教授 (70187475)
• Co-Investigator(Kenkyū-buntansha): CHIBA Takuya 長崎大学, 大学院・医歯薬学総合研究科, 准教授 (40336152) ; YAMAZA Haruyoshi 長崎大学, 大学院・医歯薬学総合研究科 (30336151) ; HIGAMI Yoshikazu 東京理科大学, 薬学部, 教授 (90253640)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: カロリー制限 / 老化 / Neuropeptide Y

Research Abstract

カロリー制限(CR)の抗老化効果におけるNeuropeptide Y (NPY)の役割を実証するために、NPYノックアウト(KO)マウスを自由摂食(AL)、CR下で飼育し、寿命や酸化ストレスに対する耐性をテストした。1) 寿命 : NPY-koマウスの生存率はAL, CRいずれの条件でも野生型マウスよりも低かった。2) 酸化ストレス耐性 : NPY-KOマウスでは、CRの効果(ストレス耐性)が減弱した。以上の結果から、CRの抗老化効果には、NPYが重要な役割を果たしていることが示唆された。

Research Products

• [Journal Article] カロリー制限の抗老化機構 (2009)
  • Author(s): 下川功
  • Journal Title: 細胞 (印刷中)
• [Journal Article] 老化の基本メカニズムとアンチエイジング (2009)
  • Author(s): 下川功
  • Journal Title: 日本臨床 (印刷中)
• [Journal Article] Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain : implications for longevity (2009)
  • Author(s): Chiba T, Inoue D, Mizuno A, Komatsu T, Fujita S, Kubota H, Luisa Tagliaro M, Park S, Trindade LS, Hayashida T, Hayashi H, Yamaza H, Higami Y, himokawa I
  • Journal Title: Neurobiol Aging 27 Pages: 474-82
  • Peer Reviewed
• [Journal Article] カロリー制限と老化 (2008)
  • Author(s): 千葉卓哉、山座治義、下川功
  • Journal Title: Surgery Frontier 2008 15 Pages: 36-40
• [Journal Article] Longevity genes : insights from calorie restriction and genetic longevity models (2008)
  • Author(s): Shimokawa I, Chiba T, Yamaza H, Komatsu T
  • Journal Title: Mol Cells 30 ; 26(5) Pages: 427-35
  • Peer Reviewed
• [Journal Article] Calorie restriction minimizes activation of insulin signaling in response to glucose : potential involvement of the growth hormone-insulin-like growth factor 1 axis (2008)
  • Author(s): Hayashi H, Yamaza H, Komatsu T, Park S, Chiba T, Higami Y, Nagayasu T, Shimokawa I
  • Journal Title: Exp Gerontol 43(9) Pages: 827-32
  • NAID: 120006981679
  • Peer Reviewed
• [Journal Article] Pituitary growth hormone suppression reduces resistin expression and enhances insulin effectiveness : relationship with caloric restriction (2008)
  • Author(s): Chiba T, Yamaza H, Komatsu T, Nakayama M, Fujita S, Hayashi H, Higami Y, Shimokawa I
  • Journal Title: Exp Gerontol 43(6) Pages: 595-600
  • Peer Reviewed
• [Journal Article] Genet ic suppression of GH-IGF-1 activity, combined with lifelong caloric restri-ction, prevents age-related renal damage and prolongs the life span in rats (2008)
  • Author(s): Zha Y, Taguchi T, Nazneen A, Shimokawa I, Higami Y, Razzaque MS
  • Journal Title: Am J Nephrol 28(5) Pages: 755-64
  • Peer Reviewed
• [Journal Article] Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-ccelerated mouse strain P8 (2008)
  • Author(s): Komatsu T, Chiba T, Yamaza H, Yamashita K, Shimada A, Hoshiyama Y, Henmi T, Ohtani H, Higami Y, de Cabo R, Ingram DK, Shimokawa I
  • Journal Title: Exp Gerontol 43(4) Pages: 339-46
  • Peer Reviewed
• [Journal Article] カロリー制限による寿命延長・抗老化機構-神経内分泌仮説に基づく代謝調節の重要性- (2008)
  • Author(s): 千葉卓哉、山座治義、下川功
  • Journal Title: 基礎老化研究 Vol.32, No.3 Pages: 15-20
  • NAID: 10024377776
  • Peer Reviewed
• [Journal Article] Longevity genes : insights from calorie restriction and genetic longevity models. (2008)
  • Author(s): Shimokawa I.
  • Journal Title: Molecules & Cells 26 Pages: 427-435
  • Peer Reviewed
• [Journal Article] Calorie restriction minimizes activation of insulin signaling inresponse to glucose : potential involvement of the growth hormone-insulin-like growth factor 1 axis. (2008)
  • Author(s): Hayashi H.
  • Journal Title: Experimental Gerontology 43 Pages: 827-832
  • Peer Reviewed
• [Journal Article] Pituitary growth hormone suppression reduces resistin expression and enhances insulin effectiveness : relationship with caloric restriction (2008)
  • Author(s): Chiba T
  • Journal Title: Experimental Gerontology 43 Pages: 595-560
  • Peer Reviewed
• [Journal Article] Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain: Implications for longevity (2008)
  • Author(s): Chiba, T
  • Journal Title: Neurobiol Aging (印刷中)
  • Peer Reviewed
• [Journal Article] Identification of fasting-induced genes in the rat hypothalamus : relationship with neuroprotection (2007)
  • Author(s): Chiba T, Fujita S, Kubota H, Inoue D, Mizuno A, Komatsu T, Yamaza H, Higami Y, Shimokawa I
  • Journal Title: Ann N Y Acad Sci. 1119 Pages: 216-26
  • Peer Reviewed
• [Journal Article] Down-regulation of AMP-activated protein kinase by calorie restriction in rat liver (2007)
  • Author(s): To K, Yamaza H, Komatsu T, Hayashida T, Hayashi H, Toyama H, Chiba T, Higami Y, Shimokawa I
  • Journal Title: Exp Gerontol 42(11) Pages: 1063-71
  • Peer Reviewed
• [Journal Article] Involvement of insulin-like growth factor-1 in the effect of caloric restriction : regulation of plasma adiponectin and leptin (2007)
  • Author(s): Yamaza H, Komatsu T, To K, Toyama H, Chiba T, Higami Y, Shimokawa I
  • Journal Title: J Gerontol A Biol Sci Med Sci. 62(1) Pages: 27-33
  • Peer Reviewed
• [Journal Article] Identification of fasting-induced genes in the rat hypothalamus: relationship with neuroprotection (2007)
  • Author(s): Chiba, T
  • Journal Title: Ann N Y Acad Sci. 1119 Pages: 216-226
  • Peer Reviewed
• [Presentation] The mechanism underlying the effect of calorie restriction : An insight from longevity genes (2009)
  • Author(s): Shimokawa I
  • Organizer: The 2nd Hallym-Nagasaki International Joint Meeting on Aging & Neurodegenerative Diseases. Pyeongchon, Seoul
  • Place of Presentation: Korea
  • Year and Date: 2009-02-09
• [Presentation] Longevity genes with special reference to the mechanism underlying the effect of calorie restriction (2008)
  • Author(s): Shimokawa I
  • Organizer: The 10th International Symposium : Vascular aging : Molecular exploration and microinflammatory implications
  • Place of Presentation: Pusan National University, Korea
  • Year and Date: 2008-12-12
• [Presentation] Calorie restriction modulates insulin signaling through suppress ion of growth hormone (2008)
  • Author(s): Shimokawa l
  • Organizer: The 9^<th> International Congress on Cell Biology
  • Place of Presentation: ソウル、韓国
  • Year and Date: 2008-10-07
• [Presentation] 分子レベルからみたアンチエイジング・抗酸化サプリのこれから (2008)
  • Author(s): 下川功
  • Organizer: 日本抗加齢医学会 Educational Seminar
  • Place of Presentation: 東京
  • Year and Date: 2008-09-16
• [Presentation] カロリー制限による老化遅延、加齢病態抑制のメカニズム. ワークショップ「老化機構解明のための病理学的アプローチ」 (2008)
  • Author(s): 下川功
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2008-05-15
• [Presentation] Chungnam National University Annual Symposium on Microbiology and Molecular Genetics (2008)
  • Author(s): Shimokawa I
  • Organizer: A role for growth hormone in the anti-aging effect of calorie restriction
  • Place of Presentation: Daejeon, Korea
  • Year and Date: 2008-02-15
• [Presentation] Calorie restriction modulates insulin signaling through suppression of growth hormo ne. In Symposium "Aging and anti-aging" (2008)
  • Author(s): Shimokawa I
  • Organizer: The 9th International Congress on Cell Biology
  • Place of Presentation: Seoul, Korea
• [Presentation] Calorie restriction increases TORC2-dependent CREB activity for induction of gluconeogenetic gene expression by down-regulation of AMPK (2008)
  • Author(s): Lucas S. Trindade, Komatsu T, Yamaza H, Chiba T,Higami Y,Shimokawa I
  • Organizer: 第31回日本基礎老化学会
  • Place of Presentation: 松本
• [Presentation] Caloric restriction upregulates the Akt-Glut pathway in the white adipose tissue possibly through moderate suppression of growth hormone (2008)
  • Author(s): Seongjoon Park, Komatsu T, Yamaza H, Chiba T,Higami Y,Shimokawa I
  • Organizer: 第31回日本基礎老化学会
  • Place of Presentation: 松本
• [Presentation] 教育講演「カロリー制限とアンチエイジング」 (2007)
  • Author(s): 下川 功
  • Organizer: 第20回日本老年泌尿器科学会
  • Place of Presentation: 長崎
  • Year and Date: 2007-05-12
• [Presentation] foxO1 is not involved in the calorie restriction - specific response to oxidative stress in mice liver (2007)
  • Author(s): Komatsu T, Fukumoto Y, Mashima H, Furuyama T, Chiba T, Yamaza H, Higami H, Shimokawa I
  • Organizer: 36th Annual Meeting of American Aging Association
  • Place of Presentation: San Antonio, TX USA
• [Book] A transgenic dwarf rat strain as a tool for the study of immunosenescence in aging rats and the effect of calorie restriction. In Handbook of Immunosenescence (2009)
  • Author(s): Shimokawa I, Utsuyama M, Komatsu T,Yamaza H, Chiba T, Fulop T et al.(Eds.)
  • Publisher: Springer Science+ Business Media B.V.
• [Book] カロリー制限. 新老年学3版 (2009)
  • Author(s): 下川功, 大内尉義、他編
  • Publisher: 東京大学出版会
• [Book] Handbook on Immunosenescence (2009)
  • Author(s): Shimokawa I
  • Publisher: Springer Science+Business Media B. V.
• [Book] 内分泌モデル(GH/IGF-I)動物「老化・老年病研究のための動物実験ガイドブック」 (2008)
  • Author(s): 千葉卓哉、山座治義、下川功
  • Publisher: 基礎老化学会編、アドスリー
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/pathlgy1/index/index.htm
• [Remarks] 日韓共同セミナー開催(2008年9月4-6日、長崎) : The Japan-Korea Joint Seminar (AACL2008)-Toward the establishment ofAsian Aging Research and Education Center.I. Shimokawa (Organizer), September 4-6,2008 in Huis Ten Bosch, Nagasaki
  • URL: http://www.med.nagasaki-u.ac.jp/pathlgy1/AACL2008/index.html
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/pathlgy1/index/index.htm
• [Patent(Industrial Property Rights)] 寿命延長関連遺伝子およびその用途 (2007)
  • Inventor(s): 千葉卓哉、下川功、樋上賀一、山座治義
  • Industrial Property Rights Holder: 国立大学法人長崎大学
  • Industrial Property Number: 2007-061075
  • Filing Date: 2007-03-07