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​​​​​​Aging-US: Reduced uremic metabolites are prominent feature of sarcopenia

09-21-2021

Aging-US published "Reduced uremic metabolites are prominent feature of sarcopenia, distinct from antioxidative markers for frailty" which reported that due to global aging, frailty and sarcopenia are increasing.

Sarcopenia is defined as loss of volume and strength of skeletal muscle in elderlies, while frailty involves multiple domains of aging-related dysfunction, impaired cognition, hypomobility, and decreased social activity. Here the authors analyzed comprehensive metabolomic data of human blood in relation to sarcopenia, previously collected from 19 elderly participants in their frailty study. These comprise TCA cycle, urea cycle, nitrogen, and methylated metabolites.

Dr. Mitsuhiro Yanagida and Dr. Hiroshi Kondoh said, "Due to the wave of global aging, aging-related diseases among the elderly are increasing: hypertension, diabetes, atherosclerosis, osteoporosis, dementia, cancer, etc."

Frailty and sarcopenia are also well known as aging-related diseases. Both diseases are increasing with estimated global populations of about 120 million and 90 million individuals, respectively. The clinical evaluation for sarcopenia is different from that for frailty. Sarcopenia is defined as a loss of skeletal muscle and muscle strength in the elderly, while frailty is a state of vulnerability to several stressors, due to declined function or impairment of organs and tissues during aging.

Figure 1. The metabolomic study of sarcopenia. (A) Overview of the study protocol. All participants were clinically assessed, and their blood was evaluated by untargeted whole-blood metabolomics. This study was conducted using previously reported clinical data from 19 elderly participants who were also assessed for sarcopenia. (B) Comparison of SMI between sarcopenic and non-sarcopenic subjects. SMI was significantly decreased in the sarcopenia group. (C) Pearson's correlation of the linear model between hand grip and SMI (left panel). The correlation coefficient between hand grip and SMI was statistically significant (R = 0.60, p = 0.007). The correlation between MoCA-J and SMI was not statistically significant (R = 0.25, p = 0.31). (D) Serum creatine kinase levels decreased significantly in sarcopenia. (E) Serum creatinine decreased significantly in sarcopenia and the low-SMI group. (F) Metabolomic analysis by LC-MS detected a significant decrease of creatinine in sarcopenia and the low-SMI group. *p < 0.05. Error bars represent means ± SD. **p < 0.01. Error bars represent means ± SD.

Thus, the Rockwood Frailty Index and EFS are distinct from physical frailty in evaluating cognitive or social function. Several reports suggest the involvement of cytokines in sarcopenia. However, little is known about the metabolic basis which may be shared or discrete in sarcopenia and frailty.

Metabolomics is a newly developed branch of chemistry that detects and quantifies small molecules, called metabolites, using methods such as liquid chromatography-mass spectrometry. Although many studies have examined human blood serum or plasma, these authors' whole blood analysis covers metabolites from both cellular and non-cellular compartments. This approach has been validated in several comprehensive, non-targeted studies for comparisons between yeast and human blood, aging metabolites, and fasting compounds. In addition, their whole blood metabolomics have identified 15 frailty markers, including 10 antioxidants, based on EFS diagnostic tools.

Although many studies have examined human blood serum or plasma, these authors' whole blood analysis covers metabolites from both cellular and non-cellular compartments

The Yanagida/Kondoh Research team concluded in their Aging-US Research Output, "Notably, these 22 sarcopenia markers are largely distinct from 15 frailty markers in the same patients, suggesting that metabolic profiles distinguish sarcopenia from frailty. Thus, sarcopenia can be characterized as muscle aging with a decrease of metabolites for mitochondria, muscle, kidney, and methylation, in sharp contrast to the decrease of metabolites for antioxidation in frailty [28]. These findings help not only our understanding of pathogenesis of sarcopenia and frailty, but also future development of clinical applications."

Full Text - https://www.aging-us.com/article/203498/text

Correspondence to: Mitsuhiro Yanagida email: myanagid@gmail.com and Hiroshi Kondoh email: hkondoh@kuhp.kyoto-u.ac.jp

Keywords: sarcopenia, muscle mass, metabolomics, frailty, uremic metabolites

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The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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