The Muscle Metabolome Differs between Healthy and Frail Older Adults

Journal article


Fazelzadeh, Parastoo, Hangelbroek, Roland W. J., Tieland, Michael, de Groot, Lisette C. P. G. M., Verdijk, Lex B., Van Loon, Luc J.C., Smilde, Age K., Alves, Rodrigo D. A. M., Vervoort, Jacques, Müller, Michael, van Duynhoven, John P. M. and Boekschoten, Mark V.. (2016). The Muscle Metabolome Differs between Healthy and Frail Older Adults. Journal of Proteome Research. 15(2), pp. 499 - 509. https://doi.org/10.1021/acs.jproteome.5b00840
AuthorsFazelzadeh, Parastoo, Hangelbroek, Roland W. J., Tieland, Michael, de Groot, Lisette C. P. G. M., Verdijk, Lex B., Van Loon, Luc J.C., Smilde, Age K., Alves, Rodrigo D. A. M., Vervoort, Jacques, Müller, Michael, van Duynhoven, John P. M. and Boekschoten, Mark V.
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.

Keywordsaging; frailty; muscle biopsy; tissue remodeling
Year2016
JournalJournal of Proteome Research
Journal citation15 (2), pp. 499 - 509
PublisherAmerican Chemical Society
ISSN1535-3893
Digital Object Identifier (DOI)https://doi.org/10.1021/acs.jproteome.5b00840
Scopus EID2-s2.0-84957649300
Page range499 - 509
Research GroupMary MacKillop Institute for Health Research
Publisher's version
File Access Level
Controlled
Place of publicationUnited States
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