The Role of NF‐κB in Protein Breakdown in Immobilization, Aging, and Exercise: From Basic Processes to Promotion of Health
Abstract
Between the ages of 20 and 80 years, humans lose about 20–30% of their skeletal muscle weight. This phenomenon has been termed sarcopenia of old age and is directly involved in the well‐being of the aged. With aging, people tend to be less mobile and are frequently bedridden, which exacerbates the muscle weight loss. The molecular mechanisms responsible for the muscle protein breakdown during immobilization in aging have been studied in our laboratory in a model of 24‐month‐old Wistar rats, immobilized for 4 weeks. Subsequently we investigated the activation of the intracellular and extracellular proteolytic systems in the immobilized muscles. A similar group of young (6‐month‐old) rats was examined and compared to the older rats. The involvement of NF‐κB transcription factor in muscle atrophy was assessed in immobilized muscles of young and old animals. There were marked differences in the kinetics and the pattern of NF‐κB activation in young versus old muscles. It seems that in both young and old animals in the early stages of limb immobilization, an alternative pathway of NF‐κB activation can be observed. However, in late stages of immobilization, the canonic pathway of NF‐κB activation (p65/p50 complex with I‐κB α degradation) is predominant. Interestingly, the canonic activation pathway is more prominent in muscles from old animals compared to young ones. The activation of NF‐κB has been observed also in muscles subjected to acute and intense exercise, implying that inflammatory processes may take place under the conditions of intense exercise. This may cause muscle damage and protein breakdown. Therefore, using NF‐κB pathway inhibitors may prove beneficial in attenuating NF‐κB‐associated muscle damage in both disuse atrophy and strenuous exercise.
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Our finding that autophagy regulators RELA, RELB, and NFKB1 are negatively associated with outcomes is in line with previous data showing that NF-kB signaling is upregulated within aged skeletal muscle.
“Our finding that autophagy regulators RELA, RELB, and NFKB1 are negatively associated with outcomes is in line with previous data showing that NF‐kB signaling is upregulated within aged skeletal muscle (Bar‐Shai et al., 2005; Phillips & Leeuwenburgh, 2005), including a report by Buford et al. (2010), who observed higher activity of NF‐kB in older sedentary adults with low fitness, muscle mass, and”
From Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the study of muscle, mobility and aging ( <scp>SOMMA</scp> ) (2024) · cites this paper as Bar‐Shai et al., 2005
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- Authors
- BAR‐SHAI, M., CARMELI, E., & REZNICK, A. Z.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Tel Aviv University (IL)
- Corresponding author
- REZNICK, ABRAHAM Z.
- ORCID
- CARMELI, ELI
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2005-12
- Volume
- 1057
- Issue
- 1
- Pages
- 431-447
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W1979595149
- Cited by
- 67
- References
- 5
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 5
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- NF-κB, muscle protein degradation, sarcopenia, muscle atrophy, immobilization, aging, exercise-induced muscle damage, proteolytic system, IκBα degradation, inflammation, NF-κB inhibitors, disuse atrophy
- MeSH terms
- NF-KappaB Inhibitor alpha, Adult, Aged, Aged, 80 and over, Aging, Animals, Female, Humans, Immobilization, Middle Aged, Proteins, Random Allocation, Tumor Necrosis Factor-alpha, Signal Transduction, Exercise, NF-kappa B, Rats, Wistar, Muscle, Skeletal, I-kappa B Proteins, Ubiquitin, Rats
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