title: The Muscle Metabolome Differs between Healthy and Frail Older Adults.
abstract: Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects, and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference group. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies.
authors.affiliation: Top Institute Food and Nutrition , Wageningen 6709 PA, The Netherlands.|Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University , Wageningen 6700 EV, The Netherlands.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Fazelzadeh
authors.affiliation: Top Institute Food and Nutrition , Wageningen 6709 PA, The Netherlands.|Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University , Wageningen 6700 EV, The Netherlands.
authors.forename: Roland W J
authors.initials: RW
authors.lastname: Hangelbroek
authors.affiliation: Top Institute Food and Nutrition , Wageningen 6709 PA, The Netherlands.|Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University , Wageningen 6700 EV, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Tieland
authors.affiliation: Top Institute Food and Nutrition , Wageningen 6709 PA, The Netherlands.|Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University , Wageningen 6700 EV, The Netherlands.
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
authors.affiliation: Top Institute Food and Nutrition , Wageningen 6709 PA, The Netherlands.|Department of Human Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University , Maastricht 6229 ER, The Netherlands.
authors.forename: Lex B
authors.initials: LB
authors.lastname: Verdijk
authors.affiliation: Top Institute Food and Nutrition , Wageningen 6709 PA, The Netherlands.|Department of Human Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University , Maastricht 6229 ER, The Netherlands.
authors.forename: Luc J C
authors.initials: LJ
authors.lastname: van Loon
authors.affiliation: Biosystems Data Analysis Group, University of Amsterdam , Amsterdam 1090 GE, The Netherlands.
authors.forename: Age K
authors.initials: AK
authors.lastname: Smilde
authors.affiliation: Department of Analytical Biosciences, Leiden University , Leiden 2333 CC, The Netherlands.|Netherlands Metabolomics Centre , Leiden 2333 CC, The Netherlands.
authors.forename: Rodrigo D A M
authors.initials: RD
authors.lastname: Alves
authors.affiliation: Laboratory of Biochemistry, Wageningen University , Wageningen 6700 ET, The Netherlands.
authors.forename: Jacques
authors.initials: J
authors.lastname: Vervoort
authors.affiliation: Norwich Medical School, University of East Anglia , Norwich NR4 7TJ, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: Laboratory of Biophysics, Wageningen University , Wageningen 6703 HA, The Netherlands.|Netherlands Metabolomics Centre , Leiden 2333 CC, The Netherlands.
authors.forename: John P M
authors.initials: JP
authors.lastname: van Duynhoven
authors.affiliation: Top Institute Food and Nutrition , Wageningen 6709 PA, The Netherlands.|Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University , Wageningen 6700 EV, The Netherlands.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D002264:Carboxylic Acids / Q000378:metabolism; D015444:Exercise; D005260:Female; D016330:Frail Elderly; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D018482:Muscle, Skeletal / Q000378:metabolism*; D025341:Principal Component Analysis; D055815:Young Adult
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids
keywords: aging; frailty; muscle biopsy; tissue remodeling