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Review
. 2017 May 2;8(3):314-333.
doi: 10.14336/AD.2016.1101. eCollection 2017 May.

Associations among Metabolism, Circadian Rhythm and Age-Associated Diseases

Yiwei Cao  1 , Rui-Hong Wang  1
Affiliations
Review

Associations among Metabolism, Circadian Rhythm and Age-Associated Diseases

Yiwei Cao et al. Aging Dis. .

Abstract

Accumulating epidemiological studies have implicated a strong link between age associated metabolic diseases and cancer, though direct and irrefutable evidence is missing. In this review, we discuss the connection between Warburg effects and tumorigenesis, as well as adaptive responses to environment such as circadian rhythms on molecular pathways involved in metabolism. We also review the central role of the sirtuin family of proteins in physiological modulation of cellular processes and age-associated metabolic diseases. We also provide a macroscopic view of how the circadian rhythm affects metabolism and may be involved in cell metabolism reprogramming and cancer pathogenesis. The aberrations in metabolism and the circadian system may lead to age-associated diseases directly or through intermediates. These intermediates may be either mutated or reprogrammed, thus becoming responsible for chromatin modification and oncogene transcription. Integration of circadian rhythm and metabolic reprogramming in the holistic understanding of metabolic diseases and cancer may provide additional insights into human diseases.

Keywords: Age-associated diseases; Warburg effect; circadian rhythm; metabolic reprogramming; sirtuin; tumorigenesis.

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Figures

Figure 1.
Figure 1.. The metabolic cycle gates cell cycle entry
On the left is the metabolic cycle with two phases, glycolysis and respiration; different colors of circular icon represent either suppressors (blue) or oncogenes in tumorigenesis (orange); on the right is the cell cycle, in which the regulatory relationship of mediators between these two cycles have been illustrated.
Fig 2.
Fig 2.. Enhanced anabolic PI3K/Akt pathway in a cancer cell
PI3K/Akt/mTOR pathways are involved in 1. Glycolysis; 2. Cell growth; 3. Cell cycle; 4. Cell survival.
Figure 3.
Figure 3.
Regulation of PKM2 and its function in the nucleus.
Figure 4.
Figure 4.
The transcriptional and post-translational loop of circadian systems
Figure 5.
Figure 5.
Proposed mechanism relating metabolic disease and cancer
See this image and copyright information in PMC

References

    1. Calle EE, Kaaks R (2004). Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer, 4: 579-591 - PubMed
    1. Calle EE, Thun MJ (2004). Obesity and cancer. Oncogene, 23: 6365-6378 - PubMed
    1. Gallagher EJ, LeRoith D (2011). Diabetes, cancer, and metformin: connections of metabolism and cell proliferation. Ann N Y Acad Sci, 1243: 54-68 - PubMed
    1. Khandekar MJ, Cohen P, Spiegelman BM (2011). Molecular mechanisms of cancer development in obesity. Nat Rev Cancer, 11: 886-895 - PubMed
    1. Yeung S, Pan J, Lee M-H (2008). Roles of p53, MYC and HIF-1 in regulating glycolysis—the seventh hallmark of cancer. Cell Mol Life Sci, 65: 3981-3999 - PMC - PubMed

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