Effects of Circadian NAD+ oscillation on the onset of age-related diseases

• Project/Area Number: 23689013
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• 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): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000); Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: NAD代謝 / 概日時計 / 細胞老化 / NAD+代謝 / 代謝

Outline of Final Research Achievements

In this study, we found that circadian machinery is not affected by high intracellular NAD+ at cellular and systemic levels, on the other hand, low intracellular NAD+ prolongs the period of circadian clock at the cellular level. Transgenic mice with high Nampt/NAD+ in the whole body did not show any improvements or deteriorations on glucose/lipid homeostasis. Primary MEF cells with high Nampt/NAD+ showed the delay onset of cellular senescence.　These results suggest that intracellular NAD+ level in cells is associated with the maintenance of circadian clock and the onset of cellular senescence.

Research Products

• [Journal Article] Sassone-Corsi P.Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1 (2013)
  • Author(s): Bellet MM, Nakahata Y, Boudjelal M,Watts E, Mossakowska DE, Edwards KA,Cervantes M, Astarita G, Loh C, Ellis JL,Vlasuk GP
  • Journal Title: Proc. Natl. Acad. Sci.USA Volume: 110 Issue: 9 Pages: 3333-3338
  • DOI: 10.1073/pnas.1214266110
  • Peer Reviewed
• [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
• [Presentation] 時計遺伝子発現制御における Nampt/NAD+の影響 (2014)
  • Author(s): 芦森温茂
  • Organizer: 日本時間生物学会
  • Place of Presentation: 九州大学 (福岡県福岡市)
  • Year and Date: 2014-11-08 – 2014-11-09
• [Presentation] NAD+ metabolism and NAD+-dependent protein deacetylase “Sirtuins” Regulations by Circadian Clock and Aging (2014)
  • Author(s): 中畑泰和
  • Organizer: Program of Molecular Clock 2014: Epigenetic Landscape in Biological Rhythms
  • Place of Presentation: 京都大学 (京都府京都市)
  • Year and Date: 2014-03-29
  • Invited
• [Presentation] Circadian Rhythm Regulation by NAD+-dependent protein deacetylase “SIRT1” (2013)
  • Author(s): 中畑泰和
  • Organizer: 1st International Symposium of Blue Light Society
  • Place of Presentation: JPタワー (東京都千代田区)
  • Year and Date: 2013-06-06 – 2013-06-08
  • Invited