Turning over new ideas in human skeletal muscle proteostasis: What do we know and where to from here?

Changhyun Lim; James Mckendry; Matthew Lees; Philip J. Atherton; Nicholas A. Burd; Andrew M. Holwerda; Luc J. C. van Loon; Chris Mcglory; Cameron J. Mitchell; Kenneth Smith; Daniel J. Wilkinson; Tanner Stokes; Stuart M. Phillips

doi:10.1113/EP092353

Turning over new ideas in human skeletal muscle proteostasis: What do we know and where to from here?

Changhyun Lim^*, James Mckendry, Matthew Lees, Philip J. Atherton, Nicholas A. Burd, Andrew M. Holwerda, Luc J. C. van Loon, Chris Mcglory, Cameron J. Mitchell, Kenneth Smith, Daniel J. Wilkinson, Tanner Stokes, Stuart M. Phillips

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

Understanding the turnover of proteins in tissues gives information as to how external stimuli result in phenotypic change. Nowhere is such phenotypic change more conspicuous than skeletal muscle, which can be effectively remodelled by increased loading, ageing and unloading (disuse), all of which are subject to modification by nutrition and other environmental stimuli. The understanding of muscle proteome remodelling has undergone a renaissance recently with the reintroduction of deuterated water (D2O) and its ingestion to label amino acids and measure their incorporation into proteins. However, there is confusion around the use of the deuterated water methodology and the interpretation of the data it provides. Here, we provide a short review of some of the more salient features of the method and clarify some of the confusion around the method of deuterated water methods and its use in humans and how the interpretation of the data is in contrast to that of rodents.

Original language	English
Article number	EP092353
Number of pages	9
Journal	Experimental Physiology
DOIs	https://doi.org/10.1113/EP092353
Publication status	E-pub ahead of print - 1 Feb 2025

Keywords

deuterium oxide
human
phenotype
skeletal muscle
stable isotope tracer
PROTEIN-SYNTHESIS
RESISTANCE EXERCISE
DISUSE
ADAPTATIONS
ATROPHY

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Lim, C., Mckendry, J., Lees, M., Atherton, P. J., Burd, N. A., Holwerda, A. M., van Loon, L. J. C., Mcglory, C., Mitchell, C. J., Smith, K., Wilkinson, D. J., Stokes, T., & Phillips, S. M. (2025). Turning over new ideas in human skeletal muscle proteostasis: What do we know and where to from here? Experimental Physiology, Article EP092353. Advance online publication. https://doi.org/10.1113/EP092353

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title = "Turning over new ideas in human skeletal muscle proteostasis: What do we know and where to from here?",

abstract = "Understanding the turnover of proteins in tissues gives information as to how external stimuli result in phenotypic change. Nowhere is such phenotypic change more conspicuous than skeletal muscle, which can be effectively remodelled by increased loading, ageing and unloading (disuse), all of which are subject to modification by nutrition and other environmental stimuli. The understanding of muscle proteome remodelling has undergone a renaissance recently with the reintroduction of deuterated water (D2O) and its ingestion to label amino acids and measure their incorporation into proteins. However, there is confusion around the use of the deuterated water methodology and the interpretation of the data it provides. Here, we provide a short review of some of the more salient features of the method and clarify some of the confusion around the method of deuterated water methods and its use in humans and how the interpretation of the data is in contrast to that of rodents.",

keywords = "deuterium oxide, human, phenotype, skeletal muscle, stable isotope tracer, PROTEIN-SYNTHESIS, RESISTANCE EXERCISE, DISUSE, ADAPTATIONS, ATROPHY",

author = "Changhyun Lim and James Mckendry and Matthew Lees and Atherton, {Philip J.} and Burd, {Nicholas A.} and Holwerda, {Andrew M.} and {van Loon}, {Luc J. C.} and Chris Mcglory and Mitchell, {Cameron J.} and Kenneth Smith and Wilkinson, {Daniel J.} and Tanner Stokes and Phillips, {Stuart M.}",

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doi = "10.1113/EP092353",

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AU - Lim, Changhyun

AU - Mckendry, James

AU - Lees, Matthew

AU - Atherton, Philip J.

AU - Burd, Nicholas A.

AU - Holwerda, Andrew M.

AU - van Loon, Luc J. C.

AU - Mcglory, Chris

AU - Mitchell, Cameron J.

AU - Smith, Kenneth

AU - Wilkinson, Daniel J.

AU - Stokes, Tanner

AU - Phillips, Stuart M.

PY - 2025/2/1

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N2 - Understanding the turnover of proteins in tissues gives information as to how external stimuli result in phenotypic change. Nowhere is such phenotypic change more conspicuous than skeletal muscle, which can be effectively remodelled by increased loading, ageing and unloading (disuse), all of which are subject to modification by nutrition and other environmental stimuli. The understanding of muscle proteome remodelling has undergone a renaissance recently with the reintroduction of deuterated water (D2O) and its ingestion to label amino acids and measure their incorporation into proteins. However, there is confusion around the use of the deuterated water methodology and the interpretation of the data it provides. Here, we provide a short review of some of the more salient features of the method and clarify some of the confusion around the method of deuterated water methods and its use in humans and how the interpretation of the data is in contrast to that of rodents.

AB - Understanding the turnover of proteins in tissues gives information as to how external stimuli result in phenotypic change. Nowhere is such phenotypic change more conspicuous than skeletal muscle, which can be effectively remodelled by increased loading, ageing and unloading (disuse), all of which are subject to modification by nutrition and other environmental stimuli. The understanding of muscle proteome remodelling has undergone a renaissance recently with the reintroduction of deuterated water (D2O) and its ingestion to label amino acids and measure their incorporation into proteins. However, there is confusion around the use of the deuterated water methodology and the interpretation of the data it provides. Here, we provide a short review of some of the more salient features of the method and clarify some of the confusion around the method of deuterated water methods and its use in humans and how the interpretation of the data is in contrast to that of rodents.

KW - deuterium oxide

KW - human

KW - phenotype

KW - skeletal muscle

KW - stable isotope tracer

KW - PROTEIN-SYNTHESIS

KW - RESISTANCE EXERCISE

KW - DISUSE

KW - ADAPTATIONS

KW - ATROPHY

U2 - 10.1113/EP092353

DO - 10.1113/EP092353

M3 - (Systematic) Review article

SN - 0958-0670

JO - Experimental Physiology

JF - Experimental Physiology

M1 - EP092353

ER -

Turning over new ideas in human skeletal muscle proteostasis: What do we know and where to from here?

Abstract

Keywords

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