Role of autophagy in kidney aging and metabolic acidosis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: TAKABATAKE Yoshitsugu 大阪大学, 医学(系)研究科(研究院), 助教 (30403075)
• Co-Investigator(Kenkyū-buntansha): ISAKA Yoshitaka 大阪大学, 大学院医学系研究科, 准教授 (00379166)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: オートファジー / 近位尿細管 / 老化 / アシドーシス / ミトコンドリア / 慢性腎臓病

Outline of Final Research Achievements

Autophagy plays an essential role for cellular homeostasis. We have previously demonstrated that autophagy protects against ischemia-reperfusion or nephrotoxic injury. Here we tested whether autophagy is involved in kidney aging. Age-dependent high basal autophagy plays a crucial role in counteracting kidney aging through mitochondrial quality control but that lack of up-regulation of autophagic flux in response to metabolic stress with age is associated with age-related kidney diseases. Furthermore, we tested whether autophagy is involved in cellular adaptations of the proximal tubular cell against chronic metabolic acidosis through mitochondrial homeostasis. Metabolic acidosis induces autophagy in the proximal tubular cell, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. These two results provide a new therapeutic option for age-related kidney disease and acidosis by modulating autophagy.

Free Research Field

腎臓内科学