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Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
Published on: November 15, 2024
Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius.
Donna H Korzick1, Daniel R Sharda, Anne M Pruznak
1Department of Kinesiology, The Pennsylvania State University, University Park, PA, USA.
Summary
Aging exacerbates alcohol
Area of Science:
- Gerontology
- Molecular Biology
- Nutritional Science
Background:
- Aging is associated with muscle loss and altered protein metabolism.
- Chronic alcohol consumption can induce muscle catabolism.
- The combined effects of aging and alcohol on muscle protein synthesis and degradation are not fully understood.
Purpose of the Study:
- To investigate if aged rats exhibit an exaggerated protein catabolic response in skeletal muscle following chronic alcohol feeding compared to adult rats.
- To elucidate the molecular mechanisms underlying alcohol-induced muscle catabolism in aging, focusing on protein synthesis and degradation pathways.
Main Methods:
- Adult (3-month-old) and aged (18-month-old) female F344 rats were fed alcohol or control diets for 20 weeks.
- Gastrocnemius muscle was analyzed for protein synthesis, mTOR and proteasome activity, and key signaling pathway components (e.g., IGF-I, TNF-α, IL-6, AMPK, 4E-BP1, Raptor).
- Lean body mass and circulating IGF-I were also measured.
Main Results:
- Aged rats showed an exaggerated alcohol-induced reduction in lean body mass and gastrocnemius protein synthesis compared to adult rats.
- Alcohol-fed aged rats exhibited altered mTOR signaling (e.g., 4E-BP1 dephosphorylation, altered Raptor binding) and upregulation of the LKB1-AMPK-REDD1 pathway.
- While alcohol exacerbated muscle protein synthesis decline in aged rats, it did not further increase inflammatory mediators or age-related increases in atrogin-1/MuRF1 mRNA or proteasome activity.
Conclusions:
- Skeletal muscle in aged rats is more sensitive to the catabolic effects of alcohol on protein synthesis than in adult rats.
- The exaggerated catabolic response in aged rats appears to be linked to muscle-specific insulin-like growth factor-I (IGF-I) reduction and potentially mediated by the AMPK pathway.
- Alcohol's impact on protein degradation pathways (atrogin-1, MuRF1, proteasome) was not exaggerated by aging in this study.
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