Cutting edge Seminar

 

Speaker: Naoki Ito（Brain-Skeletal Muscle Connection in Aging Project Team, National Center for Geriatrics and Gerontology）

Title: Novel molecular pathogenesis of sarcopenia induced by impaired liver-skeletal muscle crosstalk during aging

 

Date&Time: 25 February (wed)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

 

Abstract:

Sarcopenia is a progressive disease characterized by an age-related decline in skeletal muscle function. The fundamental molecular pathogenesis of sarcopenia remains unclear. Our research focuses on the age-related impairment of nicotinamide adenine dinucleotide (NAD+) metabolism and inter-organ communication in sarcopenia during aging1,2. In this study, I will discuss about the novel molecular pathogenesis of sarcopenia, lactic acidosis in skeletal muscle, which is caused by impaired liver-skeletal muscle crosstalk. Systemic lactate tolerance was decreased in aged mice due to the impaired liver lactate processing capacity, which caused the accumulation of lactate and intracellular acidification, lactic acidosis, in skeletal muscle. This lactic acidosis in skeletal muscle leads to decreased NAD+ levels and subsequent skeletal muscle dysfunction. Crucially, the pharmacological activation of hypoxia-inducible factor (HIF) or the liver-specific activation of HIF1α improved age-related impairment in lactate tolerance, lactic acidosis in skeletal muscle, and sarcopenia. Our results demonstrate that lactic acidosis in skeletal muscle is a novel molecular cause of sarcopenia and highlight HIF1α in the liver as a pharmacological target for treating sarcopenia.

 

 

Reference:

Naoki Ito, Ai Takatsu, Hiromi Ito, Yuka Koike, Kiyoshi Yoshioka, Yasutomi Kamei, Shin-ichiro Imai. Slc12a8 in the lateral hypothalamus maintains energy metabolisms and skeletal muscle functions during aging. Cell Reports. 40(4). 111131. 2022.