NFκB Regulates Muscle Development and Mitochondrial Function
Open accessAbstract
Nuclear factor (NF)κB is a transcription factor that controls immune and inflammatory signaling pathways. In skeletal muscle, NFκB has been implicated in the regulation of metabolic processes and tissue mass, yet its affects on mitochondrial function in this tissue are unclear. To investigate the role of NFκB on mitochondrial function and its relationship with muscle mass across the life span, we study a mouse model with muscle-specific NFκB suppression (muscle-specific IκBα super-repressor [MISR] mice). In wild-type mice, there was a natural decline in muscle mass with aging that was accompanied by decreased mitochondrial function and mRNA expression of electron transport chain subunits. NFκB inactivation downregulated expression of PPARGC1A, and upregulated TFEB and PPARGC1B. NFκB inactivation also decreased gastrocnemius (but not soleus) muscle mass in early life (1–6 months old). Lower oxygen consumption rates occurred in gastrocnemius and soleus muscles from young MISR mice, whereas soleus (but not gastrocnemius) muscles from old MISR mice displayed increased oxygen consumption compared to age-matched controls. We conclude that the NFκB pathway plays an important role in muscle development and growth. The extent to which NFκB suppression alters mitochondrial function is age dependent and muscle specific. Finally, mitochondrial function and muscle mass are tightly associated in both genotypes and across the life span.
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Sustained inhibition of NFkB can adversely affect muscle development and mitochondrial function during early life, but its repression has no detrimental effect in adult muscle.
“very recent work has shown that sustained inhibition of NFkB can adversely affect muscle development and mitochondrial function during early life its repression has no detrimental effect in adult muscle [71].”
From Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading (2019) · cites this paper as [71]
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- Authors
- Valentine, J. M., Li, M. E., Shoelson, S. E., Zhang, N., Reddick, R. L., & Musi, N.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Joslin Diabetes Center (US)
- Corresponding author
- Musi, Nicolas
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-11-13
- Volume
- 75
- Issue
- 4
- Pages
- 647-653
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC7328192
- OpenAlex
- W2901089311
- Cited by
- 23
- References
- 35
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 1 · 2019: 3
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01-DK80157, R01-DK089229)
- American Diabetes Association (7-13-GSK)
- Biology of Aging T32 Training Grant (T32 AG021890)
- San Antonio Nathan Shock Center of Excellence on Aging Biology (P30 AG013319)
- San Antonio Claude D. Pepper Older Americans Independence Center (P30 AG044271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- NF-κB, skeletal muscle development, mitochondrial function, muscle mass, aging, IκBα super-repressor, PGC-1α, PPARGC1B, TFEB, electron transport chain, oxygen consumption, gastrocnemius, soleus muscle
- MeSH terms
- Aging, Animals, Citrate (si)-Synthase, Male, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Muscle, Oxygen Consumption, Signal Transduction, NF-kappa B, Muscle, Skeletal, Gene Expression Regulation, Developmental, Muscle Development, Mice
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