Molecular indicators of denervation in aging human skeletal muscle

Casper Soendenbroe; Mette F Heisterberg; Peter Schjerling; Anders Karlsen; Michael Kjaer; Jesper L Andersen; Abigail L Mackey

doi:10.1002/mus.26638

Molecular indicators of denervation in aging human skeletal muscle

Casper Soendenbroe, Mette F Heisterberg, Peter Schjerling, Anders Karlsen, Michael Kjaer, Jesper L Andersen, Abigail L Mackey

Abstract

INTRODUCTION: Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation.

METHODS: Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65-94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn ), and neural cell adhesion molecule (NCAM).

RESULTS: Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65-94 years) was negatively associated with AchRγ mRNA.

DISCUSSION: Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.

Original language	English
Journal	Muscle & Nerve
Volume	60
Issue number	4
Pages (from-to)	453-463
Number of pages	11
ISSN	0148-639X
DOIs	https://doi.org/10.1002/mus.26638
Publication status	Published - Oct 2019

Keywords

Aged
Aged, 80 and over
Aging/genetics
Humans
Male
Muscle Fibers, Skeletal/metabolism
Muscle, Skeletal/innervation
Myosin Heavy Chains/genetics
Neural Cell Adhesion Molecules/genetics
Quadriceps Muscle/innervation
RNA, Messenger/metabolism
Receptors, Cholinergic/genetics
Receptors, Nicotinic/genetics

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10.1002/mus.26638

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title = "Molecular indicators of denervation in aging human skeletal muscle",

abstract = "INTRODUCTION: Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation.METHODS: Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65-94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn ), and neural cell adhesion molecule (NCAM).RESULTS: Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65-94 years) was negatively associated with AchRγ mRNA.DISCUSSION: Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.",

keywords = "Aged, Aged, 80 and over, Aging/genetics, Humans, Male, Muscle Fibers, Skeletal/metabolism, Muscle, Skeletal/innervation, Myosin Heavy Chains/genetics, Neural Cell Adhesion Molecules/genetics, Quadriceps Muscle/innervation, RNA, Messenger/metabolism, Receptors, Cholinergic/genetics, Receptors, Nicotinic/genetics",

author = "Casper Soendenbroe and Heisterberg, {Mette F} and Peter Schjerling and Anders Karlsen and Michael Kjaer and Andersen, {Jesper L} and Mackey, {Abigail L}",

note = "{\textcopyright} 2019 Wiley Periodicals, Inc.",

year = "2019",

month = oct,

doi = "10.1002/mus.26638",

language = "English",

volume = "60",

pages = "453--463",

journal = "Muscle and Nerve",

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TY - JOUR

T1 - Molecular indicators of denervation in aging human skeletal muscle

AU - Soendenbroe, Casper

AU - Heisterberg, Mette F

AU - Schjerling, Peter

AU - Karlsen, Anders

AU - Kjaer, Michael

AU - Andersen, Jesper L

AU - Mackey, Abigail L

PY - 2019/10

Y1 - 2019/10

N2 - INTRODUCTION: Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation.METHODS: Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65-94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn ), and neural cell adhesion molecule (NCAM).RESULTS: Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65-94 years) was negatively associated with AchRγ mRNA.DISCUSSION: Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.

AB - INTRODUCTION: Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation.METHODS: Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65-94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn ), and neural cell adhesion molecule (NCAM).RESULTS: Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65-94 years) was negatively associated with AchRγ mRNA.DISCUSSION: Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.

KW - Aged

KW - Aged, 80 and over

KW - Aging/genetics

KW - Humans

KW - Male

KW - Muscle Fibers, Skeletal/metabolism

KW - Muscle, Skeletal/innervation

KW - Myosin Heavy Chains/genetics

KW - Neural Cell Adhesion Molecules/genetics

KW - Quadriceps Muscle/innervation

KW - RNA, Messenger/metabolism

KW - Receptors, Cholinergic/genetics

KW - Receptors, Nicotinic/genetics

U2 - 10.1002/mus.26638

DO - 10.1002/mus.26638

M3 - Journal article

C2 - 31314910

VL - 60

SP - 453

EP - 463

JO - Muscle and Nerve

JF - Muscle and Nerve

SN - 0148-639X

IS - 4

ER -

Molecular indicators of denervation in aging human skeletal muscle

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Keywords

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