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Elucidation of novel NAD synthesis pathway to develop anti-aging strategy

Research Project

Project/Area Number 18K17921
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionUniversity of Toyama

Principal Investigator

Yaku Keisuke  富山大学, 学術研究部医学系, 助教 (70761865)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsNAD代謝 / 老化 / NAD / 代謝
Outline of Final Research Achievements

Nicotiniamide adenine dinucleotide (NAD) levels in the body decline with age, while replenishment of NAD is expected to slow or reverse aging processes. In this study, we aimed to elucidate the metabolism of Nicotinamide riboside (NR) which is the effective precursor for NAD repletion. We found that NR is digested into Nicotinamide by CD157, then converted into NR by gut microbiota.

Academic Significance and Societal Importance of the Research Achievements

NADは生命維持に必須であるビタミンB3であり、その体内量を維持することが老化関連疾患の予防・治療に有効であると考えられている。NAD補充方法の中でも前駆体の経口投与は最も簡便であり、効果的なNAD前駆体の探索が行われている。本研究ではNAD補充効率が良いと期待されるNRの消化管内での動態を明らかにした。これらの結果は肥満や糖尿病などの老化関連疾患に対する介入方法を確立する上で重要な知見となる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (6 results)

  • [Journal Article] Simultaneous Measurement of Amino Acid Enantiomers in Aged Mouse Brain Samples by LC/MS/MS Combined with Derivatization Using Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA)2021

    • Author(s)
      Yamamoto Taiji、Yaku Keisuke、Nakagawa Takashi
    • Journal Title

      Metabolites

      Volume: 11 Issue: 1 Pages: 57-57

    • DOI

      10.3390/metabo11010057

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NAD+ Metabolism Regulates Preadipocyte Differentiation by Enhancing α-Ketoglutarate-Mediated Histone H3K9 Demethylation at the PPARγ Promoter2020

    • Author(s)
      Okabe Keisuke、Nawaz Allah、Nishida Yasuhiro、Yaku Keisuke、Usui Isao、Tobe Kazuyuki、Nakagawa Takashi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 586179-586179

    • DOI

      10.3389/fcell.2020.586179

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae2020

    • Author(s)
      Hanasaki Miki、Yaku Keisuke、Yamauchi Motohiro、Nakagawa Takashi、Masumoto Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21146-21146

    • DOI

      10.1038/s41598-020-78302-5

    • NAID

      120006980741

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The microRNAs miR-302b and miR-372 regulate mitochondrial metabolism via the SLC25A12 transporter, which controls MAVS-mediated antiviral innate immunity.2020

    • Author(s)
      Yasukawa K, Kinoshita D, Yaku K, Nakagawa T, Koshiba T.
    • Journal Title

      J Biol Chem.

      Volume: 295(2) Issue: 2 Pages: 444-457

    • DOI

      10.1074/jbc.ra119.010511

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Implications of altered NAD metabolism in metabolic disorders.2019

    • Author(s)
      Okabe K, Yaku K, Tobe K, Nakagawa T.
    • Journal Title

      J Biomed Sci.

      Volume: 26(1) Issue: 1 Pages: 34-34

    • DOI

      10.1186/s12929-019-0527-8

    • Related Report
      2019 Research-status Report
    • Open Access
  • [Journal Article] Implications of NAD metabolism in pathophysiology and therapeutics for neurodegenerative diseases.2019

    • Author(s)
      Hikosaka K, Yaku K, Okabe K, Nakagawa T.
    • Journal Title

      Nutr Neurosci.

      Volume: - Issue: 5 Pages: 1-17

    • DOI

      10.1080/1028415x.2019.1637504

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD).2019

    • Author(s)
      Yaku K, Okabe K, Gulshan M, Takatsu K, Okamoto H, Nakagawa T.
    • Journal Title

      Sci Rep.

      Volume: 9(1) Issue: 1 Pages: 13102-13102

    • DOI

      10.1038/s41598-019-49547-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NAD metabolism: Implications in aging and longevity2018

    • Author(s)
      Yaku Keisuke、Okabe Keisuke、Nakagawa Takashi
    • Journal Title

      Ageing Research Reviews

      Volume: 47 Pages: 1-17

    • DOI

      10.1016/j.arr.2018.05.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overexpression of Nmnat3 efficiently increases NAD and NGD levels and ameliorates age-associated insulin resistance2018

    • Author(s)
      Gulshan Maryam、Yaku Keisuke、Okabe Keisuke、Mahmood Arshad、Sasaki Tsutomu、Yamamoto Masashi、Hikosaka Keisuke、Usui Isao、Kitamura Tadahiro、Tobe Kazuyuki、Nakagawa Takashi
    • Journal Title

      Aging Cell

      Volume: 17 Issue: 4

    • DOI

      10.1111/acel.12798

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deletion of PHGDH in adipocytes improves glucose intolerance in diet-induced obese mice2018

    • Author(s)
      Okabe Keisuke、Usui Isao、Yaku Keisuke、Hirabayashi Yoshio、Tobe Kazuyuki、Nakagawa Takashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 504 Issue: 1 Pages: 309-314

    • DOI

      10.1016/j.bbrc.2018.08.180

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal SIRT1 regulates macronutrient-based diet selection through FGF21 and oxytocin signalling in mice2018

    • Author(s)
      Matsui Sho、Sasaki Tsutomu、Kohno Daisuke、Yaku Keisuke、Inutsuka Ayumu、Yokota-Hashimoto Hiromi、Kikuchi Osamu、Suga Takayoshi、Kobayashi Masaki、Yamanaka Akihiro、Harada Akihiro、Nakagawa Takashi、Onaka Tatsushi、Kitamura Tadahiro
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41467-018-07033-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NAD Metabolism in Cancer Therapeutics2018

    • Author(s)
      Yaku Keisuke、Okabe Keisuke、Hikosaka Keisuke、Nakagawa Takashi
    • Journal Title

      Frontiers in Oncology

      Volume: 8 Pages: 622-622

    • DOI

      10.3389/fonc.2018.00622

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腸管恒常性維持におけるNAD代謝の役割2021

    • Author(s)
      夜久 圭介、中川 崇
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] NAD代謝による腸管恒常性維持機構の解明2020

    • Author(s)
      夜久 圭介、中川 崇
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新規NAD合成経路の解析2019

    • Author(s)
      夜久 圭介、中川 崇
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新規NAD合成経路の発見と抗老化戦略に与える影響について2018

    • Author(s)
      夜久圭介,中川 崇
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新規NADアナログNGDの機能解析2018

    • Author(s)
      夜久圭介,中川 崇
    • Organizer
      第41回日本分子生物学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新規NAD代謝経路による抗老化機構2018

    • Author(s)
      中川 崇,夜久圭介
    • Organizer
      第41回日本分子生物学会大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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