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Regulation of the aging by calorie restriction: Implications of mitochondrial retrograde signals

Research Project

Project/Area Number 22390042
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionNagasaki University

Principal Investigator

SHIMOKAWA Isao  長崎大学, 医歯(薬)学総合研究科, 教授 (70187475)

Co-Investigator(Kenkyū-buntansha) MORI Ryoichi  長崎大学, 大学院・医歯薬学総合研究科, 講師 (30509310)
千葉 卓哉  長崎大学, 大学院・医歯薬学総合研究科, 准教授 (40336152)
Project Period (FY) 2010-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywordsカロリー制限 / 老化 / ミトコンドリア
Research Abstract

Calorie restriction (CR) may exert anti-aging effects by modulating mitochondrial functions. We previously reported that CR upregulated mitochondrial proteins, including Cox6b1, a subunit of cytochrome c oxidase (Cox). To investigate the functional roles of Cox6b1 in mitochondria, we conducted in vitro experiments using Cox6b1-overexpressing cells or knockdown cells. The findings suggest that Cox6b1 mediates some of the effects, e.g., stress resistance, of CR by enhancing mitochondrial respiration via the assembly of Cox supercomplexes. The simultaneous generation of ROS may be prevented by several mechanisms, including Nrf2 activation. We also found that inhibition of glycogen synthase kinase (GSK)-3b, a putative upstream signaling molecule for Cox6b1, increased Cox6b1 protein expression. Accordingly, we confirmed that CR increased phosphorylated GSK-3b, its inactive form, in the mouse liver. The present study supports the mitohormesis hypothesis of CR.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (46 results)

All 2014 2013 2012 2011 2010

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (26 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Primary hepatic gastrointestinal stromal tumor showing remarkable myxoid change and hemangiopericytoma-like pattern2013

    • Author(s)
      Hayashi H, Iseki M, Kawabata M, Nonoshita M, Yamamoto H, Shimokawa I
    • Journal Title

      Acta Medica Nagasakiensia

      Volume: Vol.58 Pages: 19-24

    • NAID

      110009577018

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A case of intracystic apocrine papillary tumor : Diagnostic pitfalls for malignancy2013

    • Author(s)
      Hayashi H, Ohtani H, Yamaguchi J, Shimokawa I
    • Journal Title

      Pathol Res Pract

      Volume: Vol.209 Pages: 808-811

    • NAID

      120006986734

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Do sirtuins promote mammalian longevity? A critical review on its relevance to the longevity effect induced by calorie restriction2013

    • Author(s)
      Park S,Mori R,Shimokawa I
    • Journal Title

      Mol Cells

      Volume: Vol.35 Pages: 474-480

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of lifespan extension and preventive effects of calorie restriction on tumor development : Possible link between central neuroendocrine system and peripheral metabolic adaptation2013

    • Author(s)
      Chiba T,Dong K,Nishizono S, Shimokawa I
    • Journal Title

      J Phys Fitness Sports Med

      Volume: Vol.2 Pages: 259-266

    • NAID

      10031179347

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Renoprotective effects of telmisartan after unilateral renal ablation in rats2013

    • Author(s)
      Matsuo T,Miyata Y,Sagara Y,Higami Y,Tobu S,Matsuo M,Noguchi M, Shimokawa I,Kanetake H,Sakai H
    • Journal Title

      Int J Nephrol Renovasc

      Volume: Vol.6 Pages: 207-214

    • NAID

      120006986063

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caloric restriction-associated remodeling of rat white adepose tissue : effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration2013

    • Author(s)
      Chujo Y,Fujii N,Okita N,Konishi T, Yamada A,Haruyama Y,Tashiro K,Chiba T,Shimokawa I,Higami Y
    • Journal Title

      Age(Dordr)

      Volume: Vol.35 Pages: 1143-1156

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Do sirtuins promote mammalian longevity? A critical review on its relevance to the longevity effect induced by calorie restriction2013

    • Author(s)
      Park S, Mori R, Shimokawa I.
    • Journal Title

      Mol Cells. 2013 Jun;35(6):474-80

      Volume: 35 Issue: 6 Pages: 474-80

    • DOI

      10.1007/s10059-013-0130-x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] M5総合病理CPC 記録 : 慢性呼吸不全により死亡した31歳男性2012

    • Author(s)
      安井 万里子, 坂本 光, 新宮 啓太, 平 光寿, 高藤 康, 徳満 純一, 鳥山 愛生, 永田 祐貴, 難波 夏実, 道辻 徹, 高木 理博, 石田 正之, 有吉 紅也, 林 洋子, 下川 功
    • Journal Title

      長崎医学会雑誌

      Volume: 87巻 Pages: 80-86

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] カロリー制限とホルミシス2012

    • Author(s)
      下川 功
    • Journal Title

      日本抗加齢医学会雑誌

      Volume: Vol.8 Pages: 87-91

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Microcystic adnexal earcinomaの一例2012

    • Author(s)
      林 洋子, 井関 充及, 川崎 辰彦, 下川 功
    • Journal Title

      診断病理

      Volume: Vol.029 Pages: 150-154

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Yamada K Hyperadiponectinemia protects against premature death in metabolic syndrome model mice by inhibiting AKT signaling and chronic inflammation2012

    • Author(s)
      Otabe S,Wada N,Hahinaga T,Yuan X Shimokawa I,Fukutani T,Tanaka K, Ohki T,Kakino S,Kurita Y,Nakayama H, Tajiri Y
    • Journal Title

      J Endocrinol

      Volume: Vol.213 Pages: 67-76

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein reporter bioassay systems for the phenotypic screening of candidate drugs : a mouse platform for anti-aging drug screening2012

    • Author(s)
      Chiba T,Tsuchiya T,Mori R, Shimokawa I
    • Journal Title

      Sensors(Basel)

      Volume: Vol.12 Pages: 1648-1656

    • NAID

      120006985439

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rodent Models to Study the Roles of the GH-IGF-1 Axis in the Aging and Anti-Aging Effects of Calorie Restriction2012

    • Author(s)
      Fang P, Tagliaro ML, Shimokawa I
    • Journal Title

      Open Endocrinol J

      Volume: Vol.6 Pages: 42-48

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Protein reporter bioassay systems for the phenotypic screening of candidate drugs: a mouse platform for anti-aging drug screening2012

    • Author(s)
      Chiba T, Tsuchiya T, Mori R, Shimokawa I
    • Journal Title

      Sensors (Basel)

      Volume: 12 Pages: 1648-1656

    • NAID

      120006985439

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperadipo-nectinemia protects against premature death in metabolic syndrome model mice by inhibiting AKT signaling and chronic inflammation2012

    • Author(s)
      Otabe S, Wada N, Hashinaga T, Yuan X, Shimokawa I, FukutaniT, Tanaka K, Ohki T, Kakino S, Kurita Y, Nakayama H, Tajiri Y, Yamada K
    • Journal Title

      Journal of Endocrinology

      Volume: 213 Issue: 1 Pages: 67-76

    • DOI

      10.1530/joe-11-0329

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modest inhibition of the growth hormone axis does not affect mitochondrial reactive oxygen species generation or redox state, unlike calorie restriction2011

    • Author(s)
      Hayashida T, Shimokawa I, 他
    • Journal Title

      Geriatr Gerontol Int

      Volume: 11 Issue: 4 Pages: 496-503

    • DOI

      10.1111/j.1447-0594.2011.00692.x

    • NAID

      10030468628

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pカロリー制限の抗老化効果2011

    • Author(s)
      下川功
    • Journal Title

      消化器内科

      Volume: 53 Pages: 258-263

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Modest inhibition of the growth hormone axis does not affect mitochondrial reactive oxygen species generation or redox state, unlike calorie restriction.2011

    • Author(s)
      Hayashida T, Shimokawa I, 他
    • Journal Title

      Geriatr Gerontol Int

      Volume: (印刷中)

    • NAID

      10030468628

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Longevity genes; an update2014

    • Author(s)
      Shimokawa I
    • Organizer
      The 4th Busan-Nagasaki Joint Symposium on Aging Research
    • Place of Presentation
      Busan
    • Year and Date
      2014-02-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Upregulation of cytochrome c oxidase subunit 6b1 enhances mitochondrial respiration and oxidative stress response: Possible implication in the anti-aging effect of calorie restriction2014

    • Author(s)
      Sang Eun Kim, Ryoichi Mori, Toshimitsu Komatsu, Takuya Chiba, Hiroko Hayashi, Michiru D. Sugawa, Norbert A. Dencher and Isao Shimokawa
    • Organizer
      The 4th Busan-Nagasaki Joint Symposium on Ageng Research, Busan
    • Place of Presentation
      Busan, Korea
    • Related Report
      2013 Annual Research Report
  • [Presentation] Differential regulation of cancer and lifespan by dietary restriction via FoxO1 and FoxO32013

    • Author(s)
      Shimokawa I
    • Organizer
      2013 Mini-Symposium on Mitochondria and Aging
    • Place of Presentation
      Taipei
    • Year and Date
      2013-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] A contrast between roles for FoxO1 and FoxO3 in cencer suppression and lifespan extension by dietary restriction in mice2013

    • Author(s)
      Shimokawa I
    • Organizer
      The 4th East Asia-West Pacific Region Workshop on Aging Society and Elderly Care
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-06-22
    • Related Report
      2013 Final Research Report
  • [Presentation] A key role for neuropeptide Y in lifespan extension and cancer suppression via dietary restriction2013

    • Author(s)
      Shimokawa I
    • Organizer
      Asian Association of Aging Research-2013 Seoul Symposium
    • Place of Presentation
      Seoul
    • Related Report
      2013 Final Research Report
  • [Presentation] Differential regulation of cancer and lifespan by dietary restriction via FoxO1 and FoxO32013

    • Author(s)
      Shimokawa I
    • Organizer
      Asian Aging 2013 : Japan-Korea Joint Conference on Genes, Metabolism, and Neurodegeneration
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Final Research Report
  • [Presentation] Differential regulation of cancer and lifespan by dietary restriction via FoxO1 and FoxO32013

    • Author(s)
      Shimokawa I
    • Organizer
      Cold Spring Harbor Conferences Asia
    • Place of Presentation
      China
    • Related Report
      2013 Final Research Report
  • [Presentation] カロリスにおけるニューロペプチドY の役割2013

    • Author(s)
      下川 功
    • Organizer
      第13回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel role of neuroprptide Y in mammalian aging : Linking calorie restriction to longevity2013

    • Author(s)
      Shimokawa I
    • Organizer
      The 20th World Congress of Gerontology and Geriatrics
    • Place of Presentation
      Seoul
    • Related Report
      2013 Final Research Report
  • [Presentation] カロリー制限の寿命延長, 腫瘍抑制効果におけるNeuropeptideY の役割2013

    • Author(s)
      下川 功
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] A potential role for COX6B1, a subunit of mitochondrial respiratory complex IV, in the effect of dietary restriction2012

    • Author(s)
      Shimokawa I
    • Organizer
      The 4th Hallym-Nagasaki-Exetended Joint Meeting, Aging, Re-generation and Re-construction
    • Place of Presentation
      Seoul
    • Year and Date
      2012-02-28
    • Related Report
      2013 Final Research Report
  • [Presentation] A potential role for Cox6b1, a subunit of mitochondrial respiratory complex IV, in the effect of dietary restriction2012

    • Author(s)
      Shimokawa I
    • Organizer
      The 4th Hallym-Nagasaki-Extended Joint Meeting
    • Place of Presentation
      ソウル、韓国(招待講演)
    • Year and Date
      2012-02-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] potential dietary restriction mimetics2012

    • Author(s)
      Shimokawa I , Modulators of neuropeptide Y
    • Organizer
      The 2nd Pusan-Nagasaki joint Seminar on Aging Research
    • Place of Presentation
      Pusan
    • Year and Date
      2012-02-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 次世代シーケンサーを用いたカロリー制限及び肥満マウス血漿中に存在するmicroRNAの網羅的同定2012

    • Author(s)
      森 亮一
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2013 Final Research Report
  • [Presentation] Necessity of Neuropeptide Y for the Effect of Dietary Restriction in Mice2012

    • Author(s)
      Shimokawa I
    • Organizer
      The 65th Annual Meeting of Gerontological Society of America
    • Place of Presentation
      San Diego
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of Argonute2-circulating microRNA complexes in blood plasma of calorie-restricted and high fat diet-induced obese mice2012

    • Author(s)
      Ryoichi Mori
    • Organizer
      The 4th EMBO meeting
    • Place of Presentation
      Nice(France)
    • Related Report
      2013 Final Research Report
  • [Presentation] The necessity of neuropeptide Y in the effect of dietary restriction in mice,Keystone Symposia2012

    • Author(s)
      Shimokawa I
    • Organizer
      Aging and Diseases of Aging
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of Argonute2-circulating microRNA complexes in blood plasma of calorie-restricted and high fat diet-induced obese mice2012

    • Author(s)
      森 亮一
    • Organizer
      第4回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島(広島県)
    • Related Report
      2013 Final Research Report
  • [Presentation] Differential regulation of cancer and lifespan by dietary restriction through FoxO1 and FoxO32012

    • Author(s)
      Shimokawa I
    • Organizer
      International Symposium of Asian Association of Aging Research 2012 in Fukuoka-Biology of Aging and Disorders-
    • Place of Presentation
      Fukuoka
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of Argonute2-circulating microRNA complexes in blood plasma of calorie-restricted and high fat diet-induced obese mice2012

    • Author(s)
      Ryoichi Mori
    • Organizer
      International Symposium of Asian Association of Aging Research 2012 in Fukuoka - Biology of Aging and Disorders-
    • Place of Presentation
      Tsukushi Kaikan(Fukuoka)
    • Related Report
      2013 Final Research Report
  • [Presentation] Dbf4はATM/ATRによって直接制御されるチェックポイントタンパクとして機能している2012

    • Author(s)
      Tsukushi Kaikan(Fukuoka)
    • Organizer
      第35回日本基礎老化学会
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] 「FoxOとカロリー制限」2012

    • Author(s)
      下川 功
    • Organizer
      シンポジウム「中庸の徳~インスリンシグナルと寿命,疾患」, 第12回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] A potential role for COX6B1, a subunit of mitochondrial respiratory complex IV, in the effect of dietary restriction2012

    • Author(s)
      Shimokawa I
    • Organizer
      2012 Spring Conference of the Korean Society for Gerontology and the 11th Korea-Japan Gerontologist Joint Meeting
    • Place of Presentation
      Osong
    • Related Report
      2013 Final Research Report
  • [Presentation] A potential role for COX6B1, a subunit of mitochondrial respiratory complex IV, in the effect of dietary restriction2012

    • Author(s)
      Shimokawa I
    • Organizer
      2012 Spring Conference of the Korean Society for Gerontology and the 11th Korea-Japan Gerontologist Joint meeting
    • Place of Presentation
      Osong, Korea
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The necessity of neuropeptide Y in the effect of dietary restriction in mice2012

    • Author(s)
      Shimokawa I, Chiba T, Park S, Komatsu T, Chung H, Mori R, Kusudo T, Yamashita H, Park D
    • Organizer
      Keystone Symposia, Aging and Diseases of Aging
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cytochrome c oxidase subunit VIb modulates oxidative stress in vitro2010

    • Author(s)
      Kim Sang-Eun, Shimokawa I, 他
    • Organizer
      Asian Aging Core for Longevity Research and Education 2010 Jeju Conference
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Book] 老化寿命のサイエンス第5章カロリー制限模倣物2013

    • Author(s)
      千葉 卓哉, 下川 功
    • Publisher
      羊土社
    • Related Report
      2013 Final Research Report
  • [Book] レスベラトロールの基礎と応用第7章サーチュインと老化,寿命2012

    • Author(s)
      下川 功, 千葉 卓哉, 森 亮一
    • Publisher
      シーエムシー出版
    • Related Report
      2013 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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