Pathological elucidation of age-related diseases by integrative analyses of senescence genes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293165
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Chiba University
• Principal Investigator: Yokote Koutaro 千葉大学, 医学(系)研究科(研究院), 教授 (20312944)
• Co-Investigator(Kenkyū-buntansha): 清水 孝彦 千葉大学, 医学(系)研究科(研究院), 准教授 (40301791) ; 竹本 稔 千葉大学, 医学(系)研究科(研究院), 准教授 (60447307)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 老年医学 / 老化 / 遺伝子 / 早老症 / ウェルナー

Outline of Final Research Achievements

Werner syndrome (WS) is progeroid syndrome and is caused by the recessive mutation of WRN gene. WS patients exhibit accelerated telomere shortening. However, Wrntm1Lgu, TercG4/G4 double-null mice have failed to deteriorate pathologies of Wrntm1Lgu single-null mice. In this study, to reconfirm pathological significance of telomere in a WS model, we generated Wrntm1Lgu, Terttm1Fish double-null mice and intercrossed those mice until G4 generation (TertG4/G4) to induce telomere shortening. Although both TertG4/G4 or Wrn-/-, TertG4/G4 double null mice showed significant shortening of telomere length in various organs, Wrn-/-, TertG4/G4 mice were grown without apparent abnormality in muscle, liver as well as bone. However, Wrn-/-, TertG4/G4 mice only deteriorated fat atrophy in skin and testis degeneration, but not epidermis and dermis atrophies. These results suggested that the telomere shortening by Tert deficiency is in part attributable to premature aging pathologies in WS models.

Free Research Field

老年医学