Maintenance of muscle mass and load‐induced growth in Muscle RING Finger 1 null mice with age
Open accessAbstract
Summary: Age‐related loss of muscle mass occurs to varying degrees in all individuals and has a detrimental effect on morbidity and mortality. Muscle RING Finger 1 (Mu RF 1), a muscle‐specific E3 ubiquitin ligase, is believed to mediate muscle atrophy through the ubiquitin proteasome system (UPS). Deletion of Mu RF 1 (KO) in mice attenuates the loss of muscle mass following denervation, disuse, and glucocorticoid treatment; however, its role in age‐related muscle loss is unknown. In this study, skeletal muscle from male wild‐type (WT) and Mu RF 1 KO mice was studied up to the age of 24 months. Muscle mass and fiber cross‐sectional area decreased significantly with age in WT, but not in KO mice. In aged WT muscle, significant decreases in proteasome activities, especially 20S and 26S β5 (20–40% decrease), were measured and were associated with significant increases in the maladaptive endoplasmic reticulum (ER) stress marker, CHOP. Conversely, in aged Mu RF 1 KO mice, 20S or 26S β5 proteasome activity was maintained or decreased to a lesser extent than in WT mice, and no increase in CHOP expression was measured. Examination of the growth response of older (18 months) mice to functional overload revealed that old WT mice had significantly less growth relative to young mice (1.37‐ vs. 1.83‐fold), whereas old Mu RF 1 KO mice had a normal growth response (1.74‐ vs. 1.90‐fold). These data collectively suggest that with age, Mu RF 1 plays an important role in the control of skeletal muscle mass and growth capacity through the regulation of cellular stress.
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Muscle atrophy is not yet detectable at 18 months of age.
“In the old group, Parkin overexpression was initiated at 18 months of age because muscle atrophy is not yet detectable at that time point (Hwee et al. 2014).”
From Parkin overexpression protects from ageing‐related loss of muscle mass and strength (2019) · cites this paper as Hwee et al. 2014
MuRF1 inhibition prevents age-related muscle loss but not the decrease in muscle force.
“Finally, MuRF1 inhibition prevents age-related muscle loss but not the decrease in muscle force45,46.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [45]
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- Authors
- Hwee, D. T., Baehr, L. M., Philp, A., Baar, K., & Bodine, S. C.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Bodine, Sue C.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2013-09-12
- Volume
- 13
- Issue
- 1
- Pages
- 92-101
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3947038
- OpenAlex
- W2056792074
- Cited by
- 121
- References
- 40
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 7 · 2023: 9 · 2022: 4 · 2021: 11 · 2020: 13 · 2019: 11 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 11 · 2014: 12 · 2013: 2
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Muscular Dystrophy Association
- National Institutes of Health
- Medical Research Council (MR/K00414X/1)
- National Heart, Lung, and Blood Institute (T32HL086350)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-75801, R01DK075801)
- 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
- MuRF1, E3 ubiquitin ligase, age-related muscle loss, skeletal muscle mass, muscle growth, ubiquitin-proteasome system, proteasome activity, endoplasmic reticulum stress, CHOP, sarcopenia
- MeSH terms
- Tripartite Motif Proteins, Aging, Animals, Body Weight, Capillaries, Muscle Proteins, Muscles, Organ Size, Biomarkers, Weight-Bearing, Mice, Knockout, Oxidative Stress, Muscle Fibers, Skeletal, Gene Expression Regulation, Developmental, Muscle Development, Ubiquitin, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Proteasome Endopeptidase Complex, Mice, Endoplasmic Reticulum Stress
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