Effects of NAD+ metabolism on cellular senescence/tumorigenesis

• Project/Area Number: 26830074
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: NAKAHATA Yasukazu 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (50390810)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細胞老化 / NAD+代謝 / NAD+

Outline of Final Research Achievements

We revealed that NAD+ metabolism in mouse embryonic fibroblasts affects “cellular senescence” and “tumorigenesis”. Fibroblasts derived from the mice having enforced overexpression of NAMPT, the rate-limiting enzyme in NAD+ salvage pathway delay the onset of cellular senescence and Ras-induced transformed MEF cells derived from Tg mice demonstrate less potential against anchorage-independent growth. These results suggest that in mice fibroblast to keep NAD+ level high works negative for processes of cellular senescence and tumorigenesis.

Research Products

• [Journal Article] CRY drives cyclic CK2-mediated BMAL1 phosphorylation to control the mammalian circadian clock (2015)
  • Author(s): 1)Tamaru T, Hattori M, Honda K, Nakahata Y, Sassone-Corsi P, van der Horst GTJ, Ozawa T, Takamatsu K
  • Journal Title: PLoS Biology Volume: 13 Issue: 11 Pages: e1002293-e1002293
  • DOI: 10.1371/journal.pbio.1002293
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] miR-199a links MeCP2 with mTOR signaling and its dysregulation leads to Rett Syndrome phenotypes. (2015)
  • Author(s): Tsujimura K, Irie K, Nakashima H, Egashira Y, Fukao Y, Fujiwara M, Itoh M, Uesaka M, Imamura T, Nakahata Y, Yamashita Y, Abe T, Takamori S, Nakashima K.
  • Journal Title: Cell Rep Volume: 12 Issue: 11 Pages: 1887-1901
  • DOI: 10.1016/j.celrep.2015.08.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 細胞内NAD+による概日時計遺伝子発現変動の制御 (2016)
  • Author(s): 中畑泰和, 別所康全
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-03-22
  • Invited
• [Presentation] 概日時計機構および細胞老化におけるNAD+/NAMPTの影響 (2015)
  • Author(s): 中畑泰和, 芦森温茂, 松井貴輝, 別所康全
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] NAD+の減少は、概日時計遺伝子発現周期の延長を惹起する (2015)
  • Author(s): Atsushige Ashimori, Yasukazu Nakahata, Takaaki Matsui and Yasumasa Bessho
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] CRY-driven circadian oscillation of mammalian clock protein kinase activity (2015)
  • Author(s): 田丸輝也, 服部満, 中畑泰和, 小澤岳昌, 高松研
  • Organizer: 第22回時間生物学会学術大会
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2015-11-21
• [Presentation] Reduction of intracellular NAD+ promotes the extension of periods of circadian clock genes (2015)
  • Author(s): Atsushige Ashimori, Yasukazu Nakahata, Takaaki Matsui and Yasumasa Bessho
  • Organizer: 第22回時間生物学会学術大会
  • Place of Presentation: 東京大学（東京都文京区）
  • Year and Date: 2015-11-21
• [Presentation] 概日時計～その破綻と疾病の関連性～ (2015)
  • Author(s): 中畑泰和
  • Organizer: 2014年度研究大学シンポジウム 「地域創生のための、けいはんなにおける新たな産学官ネットワークの展開」
  • Place of Presentation: リーガロイヤルホテル京都（京都府京都市）
  • Year and Date: 2015-03-30
  • Invited