Accelelration of stem cell aging and age-related disorder in premature aging model mouse

2018 Fiscal Year Final Research Report

• Project Area: Establishing a new paradigm of the pathogenesis of diseases through the understanding of stem cell aging
• Project/Area Number: 26115004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Foundation for Biomedical Research and Innovation at Kobe
• Principal Investigator: Nabeshima Yo-ichi 公益財団法人神戸医療産業都市推進機構, その他部局等, その他 (60108024)
• Project Period (FY): 2014-07-10 – 2019-03-31
• Keywords: 老化 / ビタミンD / Calpain 1 / NAD代謝 / 幹細胞の枯渇 / 幹細胞老化

Outline of Final Research Achievements

Sever cell and tissue damages are observed in lung, kidney, skin, and blood vessels of a-klotho deficient mouse in association with the occurrence of multiple aging related disorders.
We found that increased stem cell growth and followed exhaustion of stem cells were induced to compensate sever cell and tissue damages. We next analyzed metabolic abnormalities and great activation of calpain-1 observed in a-klotho deficient mouse caused cell and tissue damages and followed compensatory responses of stem cells. In addition, we analyzed the abnormality of NAD metabolism in a-klotho deficient mouse and discovered the remarkable acceleration of secondary (usually minor) pathway of NAD metabolism.

Free Research Field

分子病態学

Academic Significance and Societal Importance of the Research Achievements

老化個体における幹細胞の振る舞いについての情報、幹細胞の枯渇に関する情報はほとんどないことから、本研究成果は幹細胞老化に関する基本情報としての意義が高い。
老化に伴うNAD代謝の変化、NMNの低下は知られていただが、早期老化マウスにおいてNAD代謝の副次経路が顕著に亢進していることが初めて明らかになった意義は高い。