DOI: 10.1161/circ.148.suppl_1.12170 ISSN: 0009-7322

Abstract 12170: The Impact of Frailty on Urea Metabolism in Tanushimaru Cohort Study

Nagisa Morikawa, Mika Enomoto, Ako Fukami, Hiromi Sato, Harumi Yoshimura, Hisashi Adachi, Yoshihiro Fukumoto, Kazuo Takahashi, Kento Kitada, Yuichiro Yano, Akira Nishiyama
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Urea metabolism activation, that is urea production, is thought to be very important as a body response for water retention in the process of human evolution. However, it is not clear how that body response is changing as aging. Previous metabolomics studies suggested that various metabolites were influenced by frailty. Thus, we investigated the association between frailty and urea metabolism (urea cycle and TCA cycle) in this study.

Methods: We recruited 976 participants who had a health check-up in 2009 and were followed in 2018 in the prospective Tanushimaru cohort study. We defined people with cognitive decline ((≧28 score of Mini-Mental State Examination (MMSE) in 2009 and 24-27 score in 2018), slow gait speed (<1m/s), weaker grip strength (<28kg in men or <18kg in women) in 2018 and weight loss (difference in weight ≧ 4.5kg or 5% of weight in 2009) as “frail-like group”, while those with normal cognitive function in 2009 and 2018 and normal gait speed, grip and no weight loss in 2018 as “control group”. Among them, we extracted 10 age, sex-matched samples randomly from each group and performed targeted metabolomics by the LC/MS/MS Method Package for Primary Metabolites Ver.2 in all 20 serum samples in 2009 and 2018. We compared the activity of the metabolites between the groups and years using t-test and two-way ANOVA.

Results: Mean age of 20 samples was 70.2±5.5 years old. According to metabolomics, we found that urea increased significantly in frail-like group than in control group, while other metabolites in urea cycle were not changed. In TCA cycle, Aspartate, Aconitate and Succinate decreased in frail-like group compared to control group (Fig 1). Each metabolite activity was not significantly changed over time.

Conclusions: Increased urea was observed in elderly with frailty. Frailty was associated with not urea cycle itself but urea-associated cycle. That may indicate a possibility of the connection of frailty with urea metabolism change.

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