10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Associations among Metabolism, Circadian Rhythm and Age-Associated Diseases

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references134

          • Record: found
          • Abstract: found
          • Article: not found

          Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1.

          The pyruvate kinase isoforms PKM1 and PKM2 are alternatively spliced products of the PKM2 gene. PKM2, but not PKM1, alters glucose metabolism in cancer cells and contributes to tumorigenesis by mechanisms that are not explained by its known biochemical activity. We show that PKM2 gene transcription is activated by hypoxia-inducible factor 1 (HIF-1). PKM2 interacts directly with the HIF-1α subunit and promotes transactivation of HIF-1 target genes by enhancing HIF-1 binding and p300 recruitment to hypoxia response elements, whereas PKM1 fails to regulate HIF-1 activity. Interaction of PKM2 with prolyl hydroxylase 3 (PHD3) enhances PKM2 binding to HIF-1α and PKM2 coactivator function. Mass spectrometry and anti-hydroxyproline antibody assays demonstrate PKM2 hydroxylation on proline-403/408. PHD3 knockdown inhibits PKM2 coactivator function, reduces glucose uptake and lactate production, and increases O(2) consumption in cancer cells. Thus, PKM2 participates in a positive feedback loop that promotes HIF-1 transactivation and reprograms glucose metabolism in cancer cells. Copyright © 2011 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo.

            AMPK is a metabolic sensor that helps maintain cellular energy homeostasis. Despite evidence linking AMPK with tumor suppressor functions, the role of AMPK in tumorigenesis and tumor metabolism is unknown. Here we show that AMPK negatively regulates aerobic glycolysis (the Warburg effect) in cancer cells and suppresses tumor growth in vivo. Genetic ablation of the α1 catalytic subunit of AMPK accelerates Myc-induced lymphomagenesis. Inactivation of AMPKα in both transformed and nontransformed cells promotes a metabolic shift to aerobic glycolysis, increased allocation of glucose carbon into lipids, and biomass accumulation. These metabolic effects require normoxic stabilization of the hypoxia-inducible factor-1α (HIF-1α), as silencing HIF-1α reverses the shift to aerobic glycolysis and the biosynthetic and proliferative advantages conferred by reduced AMPKα signaling. Together our findings suggest that AMPK activity opposes tumor development and that its loss fosters tumor progression in part by regulating cellular metabolic pathways that support cell growth and proliferation. Copyright © 2013 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.

              Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases.
                Bookmark

                Author and article information

                Contributors
                Journal
                Aging Dis
                Aging Dis
                Aging and Disease
                JKL International LLC
                2152-5250
                May 2017
                2 May 2017
                : 8
                : 3
                : 314-333
                Affiliations
                [1-ad-8-3-314]Faculty of Health Science, University of Macau, Macau, China
                [2-ad-8-3-314]Faculty of Health Science, University of Macau, Macau, China
                Author notes
                [* ]Correspondence should be addressed to: Dr. Rui-Hong Wang, Faculty of Health Sciences, University of Macau, Taipa, Macao, China. E-mail: RHWang@ 123456umac.mo
                Article
                ad-8-3-314
                10.14336/AD.2016.1101
                5440111
                7770b0f3-53c8-4214-af4f-b1c347048d04
                Copyright: © 2017 Cao, et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 9 September 2016
                : 27 October 2016
                : 1 November 2016
                Categories
                Review

                age-associated diseases,circadian rhythm,metabolic reprogramming,sirtuin,tumorigenesis,warburg effect

                Comments

                Comment on this article