Cited by 121Muscle Physiology and DisordersNutrition and Health in AgingMuscle metabolism and nutrition

Maintenance of muscle mass and load‐induced growth in Muscle RING Finger 1 null mice with age

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Hwee, Darren T., Baehr, Leslie M., Philp, Andrew, Baar, Keith, Bodine, Sue C.·2014·Aging Cell

Abstract

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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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
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
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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