ArticleThe Journal of biological chemistry2010
Muscle wasting in aged, sarcopenic rats is associated with enhanced activity of the ubiquitin proteasome pathway.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.
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Who cites it
134 citing papers in PubMed, 225 citations in OpenAlex.
- Peucedanum japonicum Thunb. ameliorates age-related muscle loss by improving mitochondrial function in aged mice.GeroScience · 2026Article
- Strengthening muscle for healthy ageing: innovative treatments for sarcopenia.Nature reviews. Drug discovery · 2026Review
- Interactions Between E3 Ubiquitin Ligases and Deubiquitinases in AKT Regulation: Implications in Skeletal Muscle Homeostasis.Cell biochemistry and function · 2026Review
- Article
- The Role of Fibro/adipogenic Progenitors (FAPs) in Sarcopenia: Mechanisms and Potential Therapeutic Strategies.Stem cell reviews and reports · 2026Review
- Niclosamide extends health span and reduces frailty by ameliorating mTORC1 hyperactivation in aging models.Journal of advanced research · 2026Article
- Cryptotaenia japonica extract attenuates glucocorticoid-induced muscle atrophy via regulation of the AKT/mTOR-FOXO/E3 ubiquitin ligase axis.Frontiers in physiology · 2026Article
- Glycosylation in neuroinflammation: mechanisms, implications, and therapeutic strategies for neurodegenerative diseases.Translational neurodegeneration · 2025Review
- Interaction of Programmed Obesity and Postnatal High Fat Diet but Not (-)-Epicatechin Treatment Modifies Muscle Atrophy Proteins Levels in Male Wistar Rats.Cell biochemistry and biophysics · 2025Article
- Article
- Short-Term Severe Energy Restriction Promotes Molecular Health and Reverses Aging Signatures in Adults With Prediabetes in the PREVIEW Study.Aging cell · 2025Article
- Heat-KilledBiomedicines · 2025Article
- PI31 is a positive regulator of 20S immunoproteasome assembly.Journal of cell science · 2025Article
- Chaperone Proteins: The Rising Players in Muscle Atrophy.Journal of cachexia, sarcopenia and muscle · 2025Review
- SMN Deficiency Induces an Early Non-Atrophic Myopathy with Alterations in the Contractile and Excitatory Coupling Machinery of Skeletal Myofibers in the SMN∆7 Mouse Model of Spinal Muscular Atrophy.International journal of molecular sciences · 2024Article
- Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.Antioxidants (Basel, Switzerland) · 2024Article
- Aging Skeletal Muscles: What Are the Mechanisms of Age-Related Loss of Strength and Muscle Mass, and Can We Impede Its Development and Progression?International journal of molecular sciences · 2024Review
- The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging.Molecular biology of the cell · 2024Article
- Deubiquitinases in muscle physiology and disorders.Biochemical Society transactions · 2024Review
- YTHDF2 governs muscle size through a targeted modulation of proteostasis.Nature communications · 2024Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Among the hallmarks of aged organisms are an accumulation of misfolded proteins and a reduction in skeletal muscle mass ("sarcopenia"). We have examined the effects of aging and dietary restriction (which retards many age-related changes) on components of the ubiquitin proteasome system (UPS) in muscle. The hindlimb muscles of aged (30 months old) rats showed a marked loss of muscle mass and contained 2-3-fold higher levels of 26S proteasomes than those of adult (4 months old) controls. 26S proteasomes purified from muscles of aged and adult rats showed a similar capacity to degrade peptides, proteins, and an ubiquitylated substrate, but differed in levels of proteasome-associated proteins (e.g. the ubiquitin ligase E6AP and deubiquitylating enzyme USP14). Also, the activities of many other deubiquitylating enzymes were greatly enhanced in the aged muscles. Nevertheless, their content of polyubiquitylated proteins was higher than in adult animals. The aged muscles contained higher levels of the ubiquitin ligase CHIP, involved in eliminating misfolded proteins, and MuRF1, which ubiquitylates myofibrillar proteins. These muscles differed from ones rapidly atrophying due to disease, fasting, or disuse in that Atrogin-1/MAFbx expression was low and not inducible by glucocorticoids. Thus, the muscles of aged rats showed many adaptations indicating enhanced proteolysis by the UPS, which may enhance their capacity to eliminate misfolded proteins and seems to contribute to the sarcopenia. Accordingly, dietary restriction decreased or prevented the aging-associated increases in proteasomes and other UPS components and reduced muscle wasting.
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