Contributions of the ubiquitin-proteasome pathway and apoptosis to human skeletal muscle wasting with age
Abstract
The primary mechanism that contributes to decreasing skeletal muscle strength and size with healthy aging is not presently known. This study examined the contribution of the ubiquitin-proteasome pathway and apoptosis to skeletal muscle wasting in older adults (n = 21; mean age = 72.76 +/- 8.31 years) and young controls (n = 21; mean age = 21.48 +/- 2.93 years). Subjects underwent a percutaneous muscle biopsy of the vastus lateralis to determine: (1) ubiquitin ligase gene expression (MAFbx and MuRF1); (2) frequency of apoptosis; and (3) individual fiber type and cross-sectional area. In addition, a whole muscle strength test was also performed. A one-way ANOVA revealed significant increases in the number of positive TUNEL cells in older adults (87%; p < 0.05), although no significant increase in caspase-3/7 activity was detected. Additionally, ubiquitin ligase gene expression, individual muscle fiber type and CSA were not different between old and young subjects. Muscle strength was also significantly lower in old compared to young subjects (p < 0.05). In conclusion, this study indicates a preferential role for apoptosis contributing to decreases in muscle function with age.
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Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents and humans.
“Apoptosis signaling has been reported in muscle and neuronal cells of aged rodents (4, 7, 26, 34, 47, 77, 88, 130), and humans (44, 145).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [145]
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- Authors
- Whitman, S. A., Wacker, M. J., Richmond, S. R., & Godard, M. P.
- Affiliations
- University of Kansas (US)
- Corresponding author
- Godard, Michael P.
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2005-06-11
- Volume
- 450
- Issue
- 6
- Pages
- 437-446
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W2076842664
- Cited by
- 156
- References
- 38
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 11 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 12 · 2014: 10 · 2013: 9 · 2012: 10
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (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
- skeletal muscle atrophy, sarcopenia, aging, ubiquitin-proteasome system, apoptosis, ubiquitin ligase, atrogin-1, MuRF1, TUNEL, caspase 3/7, muscle fiber type, cross-sectional area, muscle strength, vastus lateralis, older adults
- MeSH terms
- Tripartite Motif Proteins, Adolescent, Adult, Aged, Aging, Female, Humans, Male, Muscle Proteins, Muscular Atrophy, Polymerase Chain Reaction, Apoptosis, Muscle, Skeletal, In Situ Nick-End Labeling, Ubiquitin, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Proteasome Endopeptidase Complex
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