| Project/Area Number |
18K11072
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 59040:Nutrition science and health science-related
|
|---|
| Research Institution | Shimane University |
|---|
Principal Investigator |
Hara Nobumasa 島根大学, 学術研究院医学・看護学系, 講師 (20284028)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | NAD+ / サーチュイン / Nampt / sirtuin / NAD+代謝 / ニコチンアミドホスホリボシルトランスフェラーゼ / ポリ（ADP-リボース)ポリメラーゼ / ニコチンアミド ホスホリボシルトランスフェラーゼ / ポリ（ADP-リボース）ポリメラーゼ / PARP-1 |
|---|
| Outline of Final Research Achievements |
We have found that cellular NAD+ concentrations ([NAD+]), the rates of the synthesis and breakdown of NAD+ are maintained within a narrow range in various mammalian cells including primary cultured cardiomyocytes under the resting conditions. We have also found that [NAD+] moderately increases upon induction of the rate-limiting enzyme in NAD+ synthesis. The moderate increase in cellular [NAD+] likely results from suppressed increase in NAD+ synthesis and the balanced increase in its breakdown. Many studies suggest that cellular NAD+ levels fall during aging and in age-related diseases such as metabolic syndrome, neurodegeneration, and cancer, and that raising the NAD+ levels back to normal healthy levels promotes healthy aging and delays the age-related diseases. Future elucidation of the molecular basis of the tight link between the NAD+ synthesis and its breakdown should provide an important cue toward the NAD+-boosting strategy to prevent and treat the age-related diseases.
|
| Academic Significance and Societal Importance of the Research Achievements |
加齢性疾患がさまざまな臓器のNAD+ レベルの減少と関連し、NAD+ レベルを増加させ、長寿に関わるとされるNAD+ 依存性脱アセチル化酵素サーチュイン（SIRT）を活性化することがこれら疾患の予防および治療に有益であると考えられている。そのため細胞内NAD+ 濃度（[NAD+]）制御の機序解明は重要である。本研究のNAD+ 合成と分解の緊密な連関のメカニズムの解明は、[NAD+]を増加させSIRTを活性化すること、従って加齢性疾患の予防および治療につながるものと期待される。
|
