2022 Fiscal Year Final Research Report
Exploration of treatment against skeletal muscle Akt-centered aging by elucidating the underlying regulatory mechanisms
Project/Area Number |
20K08857
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54040:Metabolism and endocrinology-related
|
Research Institution | The University of Tokyo |
Principal Investigator |
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Keywords | サルコペニア / 糖尿病 / 老化 / インスリン抵抗性 / 骨粗鬆症 |
Outline of Final Research Achievements |
In order to examine responses against under-nutrition in sarcopenia, we fasted the mAktDKO mice, a sarcopenia model, for 24 hours, and they showed significantly lower blood glucose. We also performed caloric restriction experiments, which is generally expected to suppress aging, but the lifespan of the KO mice was markedly shortened, contrary to the established theory. These data suggest that sarcopenia could be susceptible to under-nutrition and excessive diet therapy could be rather harmful in clinical practice. Moreover, fast-twitch muscle mass was partially recovered by administration of a FoxO inhibitor for 4 weeks, in parallel with the data of the FoxO knockout mice, suggesting the potential effect of chemical inhibition of the FoxO pathway against sarcopenia. We also found that transplanted melanoma cells to the KO mice grew larger, suggesting that skeletal muscle could regulate tumor growth in remote tissues.
|
Free Research Field |
糖尿病・代謝・内分泌
|
Academic Significance and Societal Importance of the Research Achievements |
我が国では糖尿病に加えてサルコペニアの増加も重要な課題であり、また両者は密接に関連していることが知られている。 我々は本研究により、サルコペニアの病態にはインスリンシグナルの下流分子のうち、AktとFoxOが重要であり、前者の活性を保ち後者の活性を抑制することが、サルコペニアの治療につながることを明らかにした。次にサルコペニアでは他組織における腫瘍増殖が促進されることも明らかとなり、何らかの骨格筋由来の因子の可能性が想定された。一方でサルコペニアは低栄養に対して脆弱であり、糖尿病に対する食事療法は重要であるものの、サルコペニア合併での過度なエネルギー制限が有益でない可能性も示された。
|