Possible-sarcopenic screening with disturbed plasma amino acid profile in the elderly.

BACKGROUND: The mass and strength of skeletal muscle decline with age, leading to its progressive dysfunction. High-throughput metabolite profiling provides the opportunity to reveal metabolic mechanisms and the identification of biomarkers. However, the role of amino acid metabolism in possible sarcopenia remains unclear. OBJECTIVES: The aim of this study included exploring variations in plasma amino acid concentrations in elderly individuals who have possible sarcopenia and further attempting to characterize a distinctive plasma amino acid profile through targeted metabolomics. METHODS: A cross-sectional, correlational research design was used for this study. Thirty possible-sarcopenic elderly participants were recruited (n = 30), as determined by the Asian Working Group for Sarcopenia (AWGS). Meanwhile, a reference group of non-sarcopenic (sex-, age-, and Appendicular Skeletal muscle Mass Index (ASMI)-matched non-sarcopenic controls, n = 36) individuals was included to compare the potential differences in metabolic fingerprint of the plasma amino acids associated with sarcopenia. Both groups were conducted the body composition analysis, physical function examination, and plasma amino acid-targeted metabolomics. The amino acids in plasma were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Also, orthogonal partial least-squares-discriminant analysis (OPLS-DA) was applied to characterize the plasma amino acid profile. RESULTS: With respect to Handgrip Strength (HGS), the Five-Repetition Chair Stand Test (CS-5), the Six-Minute Walking Test (6MWT), the arm curl, the 30 s-Chair Stand Test (CST), the 2-Minute Step Test (2MST), the Timed Up-and-Go Test (TUGT), there was a decline in skeletal muscle function in the possible-sarcopenic group compared to the non-sarcopenic group. The mean plasma concentrations of arginine, asparagine, phenylalanine, serine, lysine, glutamine, and threonine were significantly lower in the possible sarcopenia group, whereas cirulline, proline, serine, and glutamic acid concentrations were higher. According to the multi-analysis, glutamine, serine, lysine, threonine, and proline were determined as the potential markers that indicated possible sarcopenia. CONCLUSIONS: The findings characterize significantly altered plasma amino acid metabolisms in the elderly with possible sarcopenia, which aids to screening people who are at a high risk of developing condition, and motivating to design new preventive and therapeutic approaches.

De novo Explorations of Sarcopenia via a Dynamic Model.

Background: The cause of sarcopenia has been observed over decades by clinical trials, which, however, are still insufficient to systematically unravel the enigma of how resistance exercise mediates skeletal muscle mass. Materials and Methods: Here, we proposed a minimal regulatory network and developed a dynamic model to rigorously investigate the mechanism of sarcopenia. Our model is consisted of eight ordinary differential equations and incorporates linear and Hill-function terms to describe positive and negative feedbacks between protein species, respectively. Results: A total of 720 samples with 10 scaled intensities were included in simulations, which revealed the expression level of AKT (maximum around 3.9-fold) and mTOR (maximum around 5.5-fold) at 3, 6, and 24 h at high intensity, and non-monotonic relation (ranging from 1.2-fold to 1.7-fold) between the graded intensities and skeletal muscle mass. Furthermore, continuous dynamics (within 24 h) of AKT, mTOR, and other proteins were obtained accordingly, and we also predicted the delaying effect with the median of maximized muscle mass shifting from 1.8-fold to 4.6-fold during a 4-fold increase of delay coefficient. Conclusion: The de novo modeling framework sheds light on the interdisciplinary methodology integrating computational approaches with experimental results, which facilitates the deeper understandings of exercise training and sarcopenia.

Treadmill training prevents bone loss by inhibition of PPARγ expression but not promoting of Runx2 expression in ovariectomized rats.

Exercise training has been reported to prevent bone loss in ovariectomized (OVX) rats and postmenopausal women. We hypothesized that treadmill training inhibited adipogenesis and enhanced osteogenesis through the regulation of adipocyte differentiation factor peroxisome proliferators-activated receptor gamma (PPARγ) and the osteogenic factor runt-related transcription factor 2 (Runx2) in a model of OVX-induced osteoporosis. To test this hypothesis, 3-month-old female Sprague-Dawley rats were divided randomly into the following groups: Sham, OVX, OVX exercised (EX), and OVX estrogen replacement (E(2)). At the end of the experiment, the bone mineral density (BMD) was detected using DEXA and the morphology change of bone tissues and uterus was observed by HE staining. The protein expression for PPARγ and Runx2 were measured by immunohistochemistry and western blot and the bone triacylglycerol (TG) was extracted by methanol/chloroform. OVX dramatically increased the number of fat vacuoles, protein levels for PPARγ and Runx2 as well as the TG level in tibiae and lumbar vertebrate. In contrast, the serum level of E(2), the lumbar vertebrate BMD as well as the proximal and distal femur BMD was significantly decreased in the OVX group. All changes induced by OVX were significantly reversed by exercise treatment except for the protein expression level of Runx2. Moreover, exercise treatment produced no estrogenic effects on uterus as evidenced by the uterus wet weight and histology. Treadmill training could prevent bone loss induced by OVX through the inhibition of adipocyte differentiation factor PPARγ rather than promoting osteogenic factor Runx2.

Effects of treadmill exercise training on liver fat accumulation and estrogen receptor alpha expression in intact and ovariectomized rats with or without estrogen replacement treatment.

To explore the mechanism(s) of exercise training on ovariectomized (OVX)-induced liver lipid disorder, we observed effects of treadmill training on liver fat accumulation and ER alpha expression in intact and ovariectomized rats. Sixty female rats were randomly assigned to six groups: Sham sedentary (S-S), Sham exercised (S-EX), ovariectomized sedentary (O-S), ovariectomized exercised (O-EX), ovariectomized injected subcutaneously with 17beta-estradiol (E(2)) (O-E(2)), and ovariectomized treated with E(2) and exercise (O-E(2)-EX). Twelve weeks after intervention, OVX resulted in significantly higher body weight gain, intra-abdominal fat mass, serum levels of total cholesterol (TC), and liver triacylglycerol (TAG) concentrations and ER alpha expression than S-S group, while the relative uterus and liver mass, serum levels of E(2), TAG, and the ratio of high density lipoprotein (HDL) to TC were markedly lower in O-S group. All of these changes were decreased in O-S rats after treatment with E(2) alone with the exception of serum TC and HDL-C levels and liver ER alpha expression. Exercise alone significantly reversed the effect of OVX on serum E(2), the ratio of HDL-C to TC and the liver and intra-abdominal fat accumulation in OVX rats. The addition of E(2) to exercise induced the same uterus and lipid profile as E(2) alone. Moreover, an additive effect of exercise and E(2) was observed on liver ER alpha expression in Sham or OVX rats. In conclusion, treadmill training alone could prevent liver fat accumulation in OVX rats and the regulation of exercise on liver ER alpha expression in both OVX and Sham rats needs the presence of physical estrogen levels.