Metabolomic Analysis of Skeletal Muscle in Aged Mice

Ran Uchitomi,Shinji Miura,Yukino Hatazawa,Yasutomi Kamei,Yusuke Ono,Mariko Fujita,Kiyoshi Yoshioka,Nanami Senoo,Takahiko Shimizu

doi:10.1038/s41598-019-46929-8

Abstract

Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function. To better understand changes in skeletal muscle during sarcopenia, we performed a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice by using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis showed clear changes in metabolites between young and aged mice. Glucose metabolism products were decreased in aged mice, specifically fructose 1,6-diphosphate (0.4-fold) and dihydroxyacetone phosphate (0.6-fold), possibly from decreased glycolytic muscle fibers. Multiple metabolic products associated with phospholipid metabolism were significantly changed in aged mice, which may reflect changes in cell membrane phospholipids of skeletal muscle. Products of polyamine metabolism, which are known to increase nucleic acid and protein synthesis, decreased in spermine (0.5-fold) and spermidine (0.6-fold) levels. By contrast, neurotransmitter levels were increased in skeletal muscle of aged mice, including acetylcholine (1.8-fold), histamine (2.6-fold), and serotonin (1.7-fold). The increase in acetylcholine might compensate for age-associated dropout of neuromuscular junctions, whereas the increases in histamine and serotonin might be due to muscle injury associated with aging. Further analysis focusing on the altered metabolites observed in this study will provide essential data for understanding aging muscles.

Highlights

Skeletal muscle is the largest organ in the human body, accounting for about 40% of body weight, and it plays important roles in exercise and energy expenditure
To better understand changes in skeletal muscle during sarcopenia, we conducted a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry (CE-TOFMS)
C57BL/6J mice were purchased from Shimizu Laboratory Supplies (Kyoto, Japan)

Summary

Introduction

Skeletal muscle is the largest organ in the human body, accounting for about 40% of body weight, and it plays important roles in exercise and energy expenditure. Epidemiological studies have shown that people with a high quantity of skeletal muscle and a fast walking speed have greater longevity[1]. We previously reported a decrease in body weight in C57BL/6 mice older than 20 months[2]. Other studies have reported that a sarcopenia phenotype is observed at age 24 months in C57BL/6 mice[3]. In aged sarcopenia model mice, fast glycolytic muscle fibers are the first to decrease[4,5] and remodeling of skeletal muscle components, such as decreased collagen gene expression, has been reported[6]. To better understand changes in skeletal muscle during sarcopenia, we conducted a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry (CE-TOFMS).

Methods

Results

Conclusion