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Exceptional longevity and stress resistance: an integrated research between iPS cell biology and epidemiology

Research Project

Project/Area Number 15KT0009
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund
Section特設分野
Research Field Neo-Gerontology
Research InstitutionKeio University

Principal Investigator

ARAI YASUMICHI  慶應義塾大学, 医学部(信濃町), 講師 (20255467)

Co-Investigator(Kenkyū-buntansha) 石崎 達郎  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (30246045)
権藤 恭之  大阪大学, 人間科学研究科, 准教授 (40250196)
神出 計  大阪大学, 医学系研究科, 教授 (80393239)
湯浅 慎介  慶應義塾大学, 医学部(信濃町), 講師 (90398628)
中岡 博史  国立遺伝学研究所, 総合遺伝研究系, 助教 (70611193)
Co-Investigator(Renkei-kenkyūsha) IKEBE Kazunori  大阪大学, 医学系研究科, 教授 (70273696)
INOUE Itsurou  国立遺伝学研究所, 人類遺伝研究部門, 教授 (00192500)
Project Period (FY) 2015-07-10 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords超百寿者 / iPS細胞 / 健康長寿 / 疫学 / 血管内皮 / 異分野連携 / 百寿者 / ストレス耐性 / iPS / 低酸素応答 / 動脈硬化 / コホート研究 / 遺伝多型
Outline of Final Research Achievements

In this project, we aimed to identify key molecules of stress resistance in supercentenarians by means of induced pluripotent stem (iPS) cells, and replicate the findings in a cohort study of older adults, the SONIC study. First, we established iPS cells-derived endothelial cells from supercentenarians, and examined key molecules of oxidative stress and hypoxic stress responses. However, transcriptional study failed to identify key molecules because of small sample size.
Alternatively, we performed QTL analysis for extracellular-superoxide dismutase (EC-SOD), a circulating antioxidative stress molecule, and identified SNP in rs1799895 as significant determinant for circulating EC-SOD. We genotyped this SNP in 1,890 subjects in the SONIC study, and found significant associations between the SNP and carotid atherosclerosis, and geriatric phenotype.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report

Research Products

(34 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research Journal Article Presentation Book Remarks

  • [Int'l Joint Research] University of Hawaii/Iowa State University/Boston University(USA)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Hawaii/Boston University(USA)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Hawaii/Havard Medical School (USA)

    • Related Report
      2015 Research-status Report
  • [Journal Article] High plasma adiponectin levels are associated with frailty in a general old-old population: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study2018

    • Author(s)
      Nagasawa, M.,Takami, Y.,Akasaka, H.,Kabayama, M.,Maeda, S.,Yokoyama, S.,Fujimoto, T.,Nozato, Y.,Imaizumi, Y.,Takeda, M.,Itoh, N.,Takeya, Y.,Yamamoto, K.,Sugimoto, K.,Nakagawa, T.,Masui, Y.,Arai, Y.,Ishizaki, T.,Ikebe, K.,Gondo, Y.,Kamide, K.,Rakugi, H.
    • Journal Title

      Geriatrics & Gerontology International

      Volume: in press

    • DOI
      10.1111/ggi.13258
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Occlusal force is correlated with cognitive function directly as well as indirectly via food intake in community-dwelling older Japanese: From the SONIC study2018

    • Author(s)
      Ikebe K, Gondo Y, Kamide K, Masui Y, Ishizaki T, Arai Y, et al.
    • Journal Title

      PLoS One

      Volume: 13

    • DOI
      10.1371/journal.pone.0190741
    • NAID
      120006486828
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carotid Plaque Score and Risk of Cardiovascular Mortality in the Oldest Old: Results from the TOOTH Study2018

    • Author(s)
      Hirata T, Arai Y, Takayama M, Abe Y, Ohkuma K, Takebayashi T.
    • Journal Title

      J Atheroscler Thromb

      Volume: in press Issue: 1 Pages: 55-64

    • DOI
      10.5551/jat.37911
    • NAID
      130006301203
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between dietary patterns and cognitive function among 70-year-old Japanese elderly: a cross-sectional analysis of the SONIC study2017

    • Author(s)
      Okubo H., Inagaki H., Gondo Y., Kamide K., Ikebe K., Masui Y., Arai Y., Ishizaki T., Sasaki S., Nakagawa T., Kabayama M., Sugimoto K., Rakugi H., Maeda Y; SONIC Study Group.
    • Journal Title

      Nutr J

      Volume: 16 Pages: 56-56

    • DOI
      10.1186/s12937-017-0273-2
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Longitudinal association of hypertension and diabetes mellitus with cognitive functioning in a general 70-year-old population: the SONIC study2017

    • Author(s)
      Ryuno H, Kamide K, Gondo Y, Kabayama M, Oguro R, Nakama C, Yokoyama S, Nagasawa M, Maeda-Hirao S, Imaizumi Y, Takeya M, Yamamoto H, Takeda M, Takami Y, Itoh N, Takeya Y, Yamamoto K, Sugimoto K, Nakagawa T, Yasumoto S, Ikebe K, Inagaki H, Masui Y, Takayama M, Arai Y, Ishizaki T, Takahashi R, Rakugi H.
    • Journal Title

      Hypertension Research

      Volume: in press Pages: 665-670

    • DOI
      10.1038/hr.2017.15
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Age verification of the longest lived man in the world2017

    • Author(s)
      Gondo, Y., Hirose, N., Yasumoto, S., Arai, Y., and Saito, Y
    • Journal Title

      Experimental Gerontology

      Volume: 99 Pages: 7-17

    • DOI
      10.1016/j.exger.2017.08.030
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relationship between atherosclerosis and occlusal support of natural teeth with mediating effect of atheroprotective nutrients: From the SONIC study2017

    • Author(s)
      Tada, S., Ikebe, K., Kamide, K., et al.
    • Journal Title

      PLoS One.

      Volume: 12

    • DOI
      10.1371/journal.pone.0182563
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Longitudinal study of factors affecting taste sense decline in old-old individuals.2017

    • Author(s)
      Ogawa T, Uota M, Ikebe, K., Arai, Y., Kamide, K., Gondo Y, Masui, Y, Ishizaki T, Inomata C, Takeshita H, Mihara Y, Hatta K, Maeda Y.
    • Journal Title

      J Oral Rehabil

      Volume: in press Pages: 22-29

    • DOI
      10.1111/joor.12454
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Demographic, phenotypic, and genetic characteristics of centenarians in Okinawa and Honshu, Japan: Part 2 Honshu, Japan.2017

    • Author(s)
      Arai Y, Sasaki T, Hirose N
    • Journal Title

      Mech Ageing Dev

      Volume: in press Pages: 30235-4

    • DOI
      10.1016/j.mad.2017.02.005
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exome-wide Association Study IdentifiesCLEC3BMissense Variant p.S106G as Being Associated With Extreme Longevity in East Asian Populations2017

    • Author(s)
      Kumpei Tanisawa, Masashi Tanaka, et al.
    • Journal Title

      The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

      Volume: 00 Pages: 1-10

    • DOI
      10.1093/gerona/glw074
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effects of the APOE ε4 Allele and Education on Cognitive Function in Japanese Centenarians.2016

    • Author(s)
      Ishioka, YL, Gondo Y, Fuku N, Inagaki H, Masui, Y, Takayama M, Abe Y, Arai, Y., Hirose N
    • Journal Title

      Age (Dordr)

      Volume: - Pages: 495-503

    • DOI
      10.1007/s11357-016-9944-8
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] rs2802292 polymorphism in the FOXO3A gene and exceptional longevity in two ethnically distinct cohorts2016

    • Author(s)
      Fuku N, Daz-Pena R, Arai Y,Abe Y, Pareja-Galeano H, Sanchis-Gomar F, Santos-Lozano A, Zempo H,Naito H,Murakami H,Miyachi M, Venturini L, Ricevuti G,Hirose N,
    • Journal Title

      Maturitas

      Volume: 92 Pages: 110-114

    • DOI
      10.1016/j.maturitas.2016.07.016
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension2016

    • Author(s)
      Morris BJ1, Chen R2, Donlon TA2, Evans DS3, Tranah GJ3, Parimi N3, Ehret GB4, Newton-Cheh C5, Seto T6, Willcox DC7, Masaki KH8, Kamide K9, Ryuno H10, Oguro R11, Nakama C11, Kabayama M10, Yamamoto K11, Sugimoto K11, Ikebe K12, Masui Y13, Arai Y14, Ishizaki T13, Gondo Y15, Rakugi H11, Willcox BJ8.
    • Journal Title

      American Journal of Hypertension

      Volume: in press Pages: 1292-1300

    • DOI
      10.1093/ajh/hpv171
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differences in the association between high blood pressure and cognitive functioning among the general Japanese population aged 70 and 80 years: The SONIC study2016

    • Author(s)
      Ryuno H, Kamide K, Gondo Y, Nakama C, Oguro R, Kabayama M, Kawai T, Kusunoki H, Yokoyama S, Imaizumi Y, Takeya M, Yamamoto H, Takeda M, Takami Y, Itoh N, Yamamoto K, Takeya Y, Sugimoto K, Nakagawa T, Ikebe K, Inagaki H, Masui Y, Ishizaki T, Takayama M, Arai Y, Takahashi R, Rakugi H.
    • Journal Title

      Hypertension Research

      Volume: in press Pages: 557-63

    • DOI
      10.1038/hr.2016.25
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The association between lower occlusal force and slower walking speed mediated by less protein intake: from SONIC study.2015

    • Author(s)
      Okada T, Ikebe K, Kagawa R, Inomata C, Takeshita H, Gondo Y, Ishioka Y, Okubo H, Kamide K, Masui Y, Takahashi R, Arai Y, Thomson WM, Maeda Y.
    • Journal Title

      Journal of American Geriatric Society

      Volume: 63 Pages: 2382-2387

    • DOI
      10.1111/jgs.13784
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disease-associated polymorphisms in 9p21 are not associated with extreme longevity.2015

    • Author(s)
      Congrains A, Kamide K, Hirose N, Arai Y, Oguro R, Nakama C, Imaizumi Y, Kawai T, Kusunoki H, Yamamoto H, Onishi-Takeya M, Takeya Y, Yamamoto K, Sugimoto K, Akasaka H, Saitoh S, Miura T, Awata N, Kato N, Katsuya T, Ikebe K, Gondo Y, Rakugi H.
    • Journal Title

      Geriatrics & Gerontology International.

      Volume: 15 Pages: 797-803

    • DOI
      10.1111/ggi.12346
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Personality, Health Behavior, and Mortality in the Very Old2017

    • Author(s)
      Takayama M, Arai Y, Hirata T, Osawa Y, Abe Y, Iinuma T, Fukumoto M, Takayama M.
    • Organizer
      International Association of Gerontology and Geriatrics 2017
    • Place of Presentation
      サンフランシスコ、米国
    • Year and Date
      2017-07-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Supercentenarian Study: The Quest for Biological Determinants of Healthy Longevity.2017

    • Author(s)
      Arai Y
    • Organizer
      French-Japanese Scientific Meeting on Neurobiology of Diseases and Ageing.
    • Place of Presentation
      フランス大使館、東京
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Urinary albumin-to creatinine ratio and carotid atherosclerosis in the very old2017

    • Author(s)
      Arai Y, Hirata T, Takayama M, Abe Y, Ishizaki T, Masui Y,Kamide K, Gondo Y.
    • Organizer
      The 21th IAGG World Congress of Gerontology and Geriatrics, San Franisco, USA
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Association of Blood Pressure With Frailty Among Community-Dwelling Older People2017

    • Author(s)
      Kabayama M., Kamide K., Gondo Y., Sugimoto K., Masui Y., Ishizaki T., Arai Y.
    • Organizer
      The 21th IAGG World Congress of Gerontology and Geriatrics, San Franisco, USA
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Paradoxical Association Between Longevity-Related Personality Traits and Mortality in Centenarians2017

    • Author(s)
      Gondo Y., Hirose N., Masui Y., Inagaki H., Arai Y.
    • Organizer
      The 21th IAGG World Congress of Gerontology and Geriatrics, San Franisco、USA
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association between Protein Intake and Change in Renal Function Among Japanese General Old Subjects.2017

    • Author(s)
      Sekiguchi, T., Kamide, K., Ikebe, K., Kabayama, M.,Arai, Y
    • Organizer
      The 21ST IAGG World Congress of Gerontology & Geriatrics, San Francisco
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Association of Genetic Variation of TOMM40 with Cognitive Declin in Older Adults: The SONIC Study2017

    • Author(s)
      Ryuno, H., Kamide, K., Kabayama, M., Sugimoto, K., Ishizaki, T., Arai, Y., Gondo, Y. and Rakugi, H.
    • Organizer
      The 21ST IAGG World Congress of Gerontology & Geriatrics. San Francisco, USA
    • Related Report
      2017 Annual Research Report
  • [Presentation] 地域一般高齢者における腎機能維持とたんぱく質摂取量との関連について―SONIC studyを用いた縦断研究―.2017

    • Author(s)
      関口敏彰,神出 計,池邉一典,龍野洋慶,樺山 舞,杉本 研,新井康通,石崎達郎,権藤恭之,樂木宏実
    • Organizer
      第59回日本老年医学会学術集会, 名古屋
    • Related Report
      2017 Annual Research Report
  • [Presentation] 地域在宅高齢者における要介護認定と生活習慣病・慢性疾患の関連性の検討(SONIC研究)2017

    • Author(s)
      清重映里,樺山 舞,龍野洋慶,杉本 研,池邉一典,新井康通,石崎達郎,権藤恭之,樂木宏実,神出 計
    • Organizer
      第59回日本老年医学会学術集会, 名古屋
    • Related Report
      2017 Annual Research Report
  • [Presentation] Supercentenarian study: translating basic aging research into geriatric practice.2016

    • Author(s)
      Arai Y
    • Organizer
      Frontiers in aging research toward healthy longevity ~健康長寿をめざした老化研究の最前線~
    • Place of Presentation
      明治安田生命ビルMY PLAZAホール、東京
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] Encyclopedia of Geropsychology2017

    • Author(s)
      Gondo,Y., Masui, Y., Kamide, K., Ikebe, K., Arai, Y., and Ishizaki, T
    • Total Pages
      10
    • Publisher
      Springer Science+Business Media Singapore
    • Related Report
      2017 Annual Research Report
  • [Remarks] 慶応義塾大学医学部百寿総合研究センター

    • URL
      http://www.keio-centenarian.com/
    • Related Report
      2017 Annual Research Report
  • [Remarks] SONIC研究

    • URL
      http://www.sonic-study.jp/
    • Related Report
      2017 Annual Research Report
  • [Remarks] 慶應義塾大学医学部百寿総合研究センター

    • URL
      http://www.keio-centenarian.com/
    • Related Report
      2016 Research-status Report
  • [Remarks] ソニック研究

    • URL
      http://www.sonic-study.jp/
    • Related Report
      2016 Research-status Report

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Published: 2015-07-14   Modified: 2019-03-29  

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