The muscle metabolome differs between healthy and frail older adults

P. Fazelzadeh, R.W.J. Hangelbroek, C.A.B. Tieland, C.P.G.M. de Groot, L. Verdijk, L.J.C. van Loon, A.K. Smilde, Rodrigo Alves Rolo, J.J.M. Vervoort, M.R. Müller, J.P.M. van Duynhoven, M.V. Boekschoten

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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.
Original languageEnglish
Pages (from-to)499-509
JournalJournal of Proteome Research
Volume15
Issue number2
DOIs
Publication statusPublished - 2016

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Frail Elderly
Metabolome
Muscle
Muscles
Branched Chain Amino Acids
Resistance Training
Healthy Volunteers
Skeletal Muscle
Metabolites
Exercise
Biopsy
Tissue
Metabolism
Somatotypes
Needs Assessment
Aging of materials
Plasmas
Quality of Life
Amino Acids
Genes

Cite this

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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.",
author = "P. Fazelzadeh and R.W.J. Hangelbroek and C.A.B. Tieland and {de Groot}, C.P.G.M. and L. Verdijk and {van Loon}, L.J.C. and A.K. Smilde and {Alves Rolo}, Rodrigo and J.J.M. Vervoort and M.R. M{\"u}ller and {van Duynhoven}, J.P.M. and M.V. Boekschoten",
year = "2016",
doi = "10.1021/acs.jproteome.5b00840",
language = "English",
volume = "15",
pages = "499--509",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
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}

The muscle metabolome differs between healthy and frail older adults. / Fazelzadeh, P.; Hangelbroek, R.W.J.; Tieland, C.A.B.; de Groot, C.P.G.M.; Verdijk, L.; van Loon, L.J.C.; Smilde, A.K.; Alves Rolo, Rodrigo; Vervoort, J.J.M.; Müller, M.R.; van Duynhoven, J.P.M.; Boekschoten, M.V.

In: Journal of Proteome Research, Vol. 15, No. 2, 2016, p. 499-509.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The muscle metabolome differs between healthy and frail older adults

AU - Fazelzadeh, P.

AU - Hangelbroek, R.W.J.

AU - Tieland, C.A.B.

AU - de Groot, C.P.G.M.

AU - Verdijk, L.

AU - van Loon, L.J.C.

AU - Smilde, A.K.

AU - Alves Rolo, Rodrigo

AU - Vervoort, J.J.M.

AU - Müller, M.R.

AU - van Duynhoven, J.P.M.

AU - Boekschoten, M.V.

PY - 2016

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N2 - 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.

AB - 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.

U2 - 10.1021/acs.jproteome.5b00840

DO - 10.1021/acs.jproteome.5b00840

M3 - Article

VL - 15

SP - 499

EP - 509

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 2

ER -