AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan
By Antero Salminen, J. Hyttinen, K. Kaarniranta. Journal of molecular medicine, 2011
837 citations recorded by the source corpus.
Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance energy metabolism while it can repress inflammatory responses linked to chronic stress, e.g., in nutritional overload and during the aging process. AMPK can inhibit endoplasmic reticulum and oxidative stresses which are involved in metabolic disorders and the aging process. Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. The activation capacity of AMPK declines in metabolic stress and with aging which could augment the metabolic diseases and accelerate the aging process. We will review the AMPK pathways involved in the inhibition of NF-κB signaling and suppression of inflammation. We also emphasize that the capacity of AMPK to repress inflammatory responses can have a significant impact on both healthspan and lifespan.
Subfields: Epidemiology, Geriatrics and Gerontology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f1dcf3c49342291fb6c73ac45e81a603e0f90773
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Citations in the corpus
- New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis (2018, background): “AMPK was found to repress macrophage NF-κB expression by upregulating expression of Sirt1, FOXO family proteins, and PGC-1α, which then decreased activation of the RelA/p65 subunit of NF-κB [170] (Fig.”
- AMPK, insulin resistance, and the metabolic syndrome. (2013, neutral): “As reviewed elsewhere, AMPK exerts actions on metabolism, inflammation, and other parameters in liver, muscle, and pancreatic β cells, similar to its effects on adipose tissue and endothelium (3, 5, 13, 123, 124).”
- Cellular and molecular mechanisms of metformin: an overview. (2012, background): “Emerging results showing the capacity of AMPK to inhibit the inflammatory responses [130] suggest that metformin may also target the inflammatory component present in the microenvironment of most”