The role of NF-κB in protein breakdown in immobilization, aging, and exercise: From basic processes to promotion of health

Marina Bar-Shai, Eli Carmeli, Abraham Z. Reznick

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)431-447
Number of pages17
JournalAnnals of the New York Academy of Sciences
StatePublished - 2005
Externally publishedYes


  • Exercise
  • Immobilization
  • NF-κB
  • Proteolysis
  • Skeletal muscle

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


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