AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan
Open accessAbstract
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.
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AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways.
“Indeed, studies have uncovered that AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants [248,249,252,253] by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways [254,255,256].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [253]
The AMPK pathway inhibits inflammation and oxidative stress by repressing the activity of NF-κB.
“The AMPK pathway is known to inhibit inflammation and oxidative stress by repressing the activity of the transcription factor, nuclear factor kappa B (NF-κB), a key inducer of inflammatory responses [59].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [59]
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- Authors
- Salminen, A., Hyttinen, J. M. T., & Kaarniranta, K.
- Affiliations
- University of Eastern Finland (FI)
- Corresponding author
- Salminen, Antero
- Venue
- Journal of Molecular Medicine
- Published
- 2011-03-23
- Volume
- 89
- Issue
- 7
- Pages
- 667-676
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- PMC
- PMC3111671
- OpenAlex
- W2115957809
- Cited by
- 866
- References
- 117
- Citations by year
- 2026: 63 · 2025: 74 · 2024: 68 · 2023: 58 · 2022: 72 · 2021: 73 · 2020: 64 · 2019: 57 · 2018: 62 · 2017: 55 · 2016: 54 · 2015: 48 · 2014: 41 · 2013: 41 · 2012: 24
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Molecular Medicine (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Itä-Suomen Yliopisto
- Academy of Finland
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- AMPK, NF-κB signaling, inflammation, aging, healthspan, lifespan, SIRT1, PGC-1α, p53, FOXO, metabolic stress, endoplasmic reticulum stress, oxidative stress, metabolic syndrome, longevity factors
- MeSH terms
- Animals, Humans, Inflammation, Longevity, Signal Transduction, NF-kappa B, AMP-Activated Protein Kinases
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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