Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle
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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CR fully prevented the impact of aging on the muscle weight to body weight ratio.
“Although CR did not attenuate the effect of aging on skeletal muscle mass, it fully prevented the impact of aging on the muscle weight to body weight ratio, a widely used index of sarcopenia (Edstrom et al., 2006; Paturi et al., 2010; Ezzat-Zadeh et al., 2017).”
From Effects of Aging and Caloric Restriction on Fiber Type Composition, Mitochondrial Morphology and Dynamics in Rat Oxidative and Glycolytic Muscles (2019) · cites this paper as Edstrom et al., 2006
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- Authors
- Edstrom, E., Altun, M., Hagglund, M., & Ulfhake, B.
- ORCID
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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