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Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

ABSTRACT: Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p?0.05 and q<0.30) associated with NDM/LDM. Decreased renal function and the immune response have been previously linked with reduced muscle density, but the mechanisms underlying these connections are less clear. Metabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (?±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle may be a compensatory antimicrobial response to protect against an elevated microbial burden.

SUBMITTER: Lustgarten MS

PROVIDER: S-EPMC6556217 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

Lustgarten Michael S MS Fielding Roger A RA

Experimental gerontology 20171010

Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle co ...[more]

PMID: 29030163

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Project description:BackgroundLower muscle and higher fat mass are characteristics of older adults; their physical function is also characterized by slower gait speed and weaker strength. However, the association between specific body composition and physical function is unclear.MethodsWe examined the association between body composition and physical performance using combined cross-sectional data of 1,821 participants from 13 clinical studies at Wake Forest University that used a consistent battery of tests. All participants were ≥60 years old and had one of the following conditions: healthy, osteoarthritis, coronary artery disease, obesity, heart failure, at elevated risk for disability, renal transplantation candidates, heart failure with preserved ejection fraction, moderate self-reported disability, hypertension, diabetes, or coronary artery disease, at high risk for cardiovascular disease. Data at enrollment from each study using uniform tools including body mass index (BMI), dual energy x-ray absorptiometry, physical performance assessment using 4 m walk speed, five chair rise time, handgrip strength, short physical performance battery (17), and Pepper Assessment Tool for Disability were analyzed.ResultsIncreased BMI was associated with slower walk speed, lower short physical performance battery, and higher Pepper Assessment Tool for Disability score. Increased percentage of body fat was associated with slower walk speed, lower hand grip strength, lower short physical performance battery scores, and higher Pepper Assessment Tool for Disability scores. Percent appendicular lean mass was associated with faster walk speed, higher handgrip strength, higher short physical performance battery, and lower Pepper Assessment Tool for Disability score. There were no significant discrepancies in relationship between body composition and physical function by gender except gender and BMI on chair-rise time.ConclusionsHigher BMI and percent body fat were associated with poor physical function while percent appendicular lean mass was associated with better physical function. There was no significant discrepancy in the by gender.

Dataset Information

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

Publications

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

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