Cited by 196Muscle Physiology and DisordersNutrition and Health in AgingMuscle metabolism and nutrition

Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle

Edstrom, E., Altun, M., Hagglund, M., Ulfhake, B.·2006·The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

Abstract

Muscle atrophy in many conditions share a common mechanism in the upregulation of the muscle-specific ubiquitin E3-ligases atrophy gene-1/muscle atrophy F-box (Atrogin-1/MAFbx) and muscle ring-finger protein 1 (MuRF1). E3-ligases are part of the ubiquitin proteasome pathway utilized for protein degradation during muscle atrophy. In this study, we provide new data to show that this is not the case in age-related loss of muscle mass (sarcopenia). On the contrary, Atrogin-1/MAFbx and MuRF1 are downregulated in skeletal muscle of 30-month-old rats, and our results suggest that AKT (protein kinase B)-mediated inactivation of forkhead box O 4 (FOXO4) underlies this suppression. The data also suggest that activation of AKT is mediated through the insulin-like growth factor-1 (IGF-1) receptor, signaling via ShcA-Grb2-GAB. Using dietary restriction, we find that it impedes sarcopenia as well as the effects of aging on AKT phosphorylation, FOXO4 phosphorylation, and Atrogin-1/MAFbx and MuRF1 transcript regulation. We conclude that sarcopenia is mechanistically different from acute atrophies induced by disuse, disease, and denervation.

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Crossref · 10.1093/gerona/61.7.663

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Authors
Edstrom, E., Altun, M., Hagglund, M., & Ulfhake, B.
Venue
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Published
2006-07-01
Volume
61
Issue
7
Pages
663-674
ISSN
  • 1079-5006 (ISSN-L)
  • 1758-535X
OpenAlex
W2148336622
Cited by
196
References
78
Citations by year
2026: 2 · 2025: 9 · 2024: 6 · 2023: 10 · 2022: 14 · 2021: 13 · 2020: 5 · 2019: 8 · 2018: 10 · 2017: 16 · 2016: 15 · 2015: 12 · 2014: 12 · 2013: 8 · 2012: 13
FWCI
2.72
Type
journal article
Language
en
Open access
closed
Locations
  • The Journals of Gerontology Series A (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
sarcopenia, skeletal muscle atrophy, atrogin-1/MAFbx, MuRF1, E3 ubiquitin ligase, ubiquitin-proteasome system, Akt signaling, FOXO4, IGF-1 receptor, dietary restriction, aging, protein degradation
MeSH terms
Tripartite Motif Proteins, Aging, Analysis of Variance, Animals, Female, Muscle Proteins, Muscular Atrophy, Blotting, Western, Signal Transduction, Down-Regulation, Rats, Sprague-Dawley, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Rats

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