Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial

Nutrition, Metabolism and Cardiovascular Diseases

Volumn 25, Issue 7, 2015, Pages 686-693

  Vigili de Kreutzenberg, S ^a   Ceolotto, G ^a   Cattelan, A ^a   Pagnin, E ^a   Mazzucato, M ^a   Garagnani, P ^b   Borelli, V ^b   Bacalini, M G ^b   Franceschi, C ^b   Fadini, G P ^a,c   Avogaro, A ^a,c  

^a UNIVERSITY OF PADOVA   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c VENETIAN INSTITUTE OF MOLECULAR MEDICINE   (Italy)

Author keywords

Aging; Dysmetabolism; Inflammation; Longevity genes; Metformin; Prediabetes

Indexed keywords

ADENYLATE KINASE; CHOLESTEROL; GLUCOSE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MAMMALIAN TARGET OF RAPAMYCIN; METFORMIN; PLACEBO; PROTEIN P53; SIRTUIN 1; ANTIDIABETIC AGENT; BIOLOGICAL MARKER; GLUCOSE BLOOD LEVEL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; POLYSACCHARIDE; SIRT1 PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ADULT; ARTICLE; BODY MASS; BODY WEIGHT; CHROMATIN; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; GENE EXPRESSION; HUMAN; IMPAIRED GLUCOSE TOLERANCE; INSULIN SENSITIVITY; LONGEVITY; MALE; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RANDOMIZED CONTROLLED TRIAL; TELOMERE; WAIST CIRCUMFERENCE; AGING; BLOOD; CELL DEATH; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; INSULIN RESISTANCE; METABOLISM; MIDDLE AGED; MONOCYTE; PREDIABETIC STATE; TELOMERE SHORTENING;

ANIMALIA;

AGING; AMP-ACTIVATED PROTEIN KINASES; BIOMARKERS; BLOOD GLUCOSE; CELL DEATH; FEMALE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; MALE; METFORMIN; MIDDLE AGED; MONOCYTES; POLYSACCHARIDES; PREDIABETIC STATE; SIRTUIN 1; TELOMERE SHORTENING; TOR SERINE-THREONINE KINASES;

EID: 84930757246     PISSN: 09394753     EISSN: 15903729     Source Type: Journal    
DOI: 10.1016/j.numecd.2015.03.007     Document Type: Article

References (48)

1. Cunningham S.A., Riosmena F., Wang J., Boyle J.P., Rolka D.B., Geiss L.S. Decreases in diabetes-free life expectancy in the U.S. and the role of obesity. Diabetes Care 2011, 34:2225-2230.
2. Kowall B., Peters A., Thorand B., Rathmann W., Meisinger C. Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study. Diabetologia 2013, 56:268-274.
3. Knowler W.C., Barrett-Connor E., Fowler S.E., Hamman R.F., Lachin J.M., Walker E.A., et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002, 346:393-403. Diabetes Prevention Program Research Group.
4. Hirsch H.A., Iliopoulos D., Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci U.S.A 2013, 110:972-977.
5. Moiseeva O., Deschênes-Simard X., St-Germain E., Igelmann S., Huot G., Cadar A.E., et al. Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-kB activation. Aging Cell 2013, 12:489-498.
6. Martin-Castillo B., Vazquez-Martin A., Oliveras-Ferraros C., Mendez J.A. Metformin and cancer: doses, mechanisms and the dandelion and hormetic phenomena. Cell Cycle 2010, 9:1057-1064.
7. Salminen A., Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 2012, 11:230-241.
8. Krysiak R., Okopien B. The effect of metformin on monocyte secretory function in simvastatin-treated patients with impaired fasting glucose. Metabolism 2013, 62:39-43.
9. Gauthier M.S., O'Brien E.L., Bigornia S., Mott M., Cacicedo J.M., Xu X.J., et al. Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans. Biochem Biophys Res Commun 2010, 404:382-387.
10. Anisimov V.N., Berstein L.M., Popovich I.G., Zabezhinski M.A., Egormin P.A., Piskunova T.S., et al. If started early in life, metformin treatment increases lifespan and postpones tumors in female SHR mice. Aging (Albany NY) 2011, 2011(3):148-157.
11. Blagoskonny M.V. Validation of anti-aging drugs by treating age-related diseases. Aging 2009, 1:281-288.
12. de Kreutzenberg S.V., Ceolotto G., Papparella I., Bortoluzzi A., Semplicini A., Dalla Man C., et al. Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms. Diabetes 2010, 59:1006-1015.
13. Avogaro A., de Kreutzenberg S.V., Fadini G.P. Insulin signaling and life span. Pflugers Arch 2010, 459:301-314.
14. Arunachalam G., Samuel S.M., Marei I., Hong Ding H., Triggle C.R. Metformin modulates hyperglycemia-induced endothelial senescence and apoptosis through SIRT1. Br J Pharmacol 2014, 171:523-535.
15. Medvedik O., Lamming D.W., Kim K.D., Sinclair D.A. MSN2 and MSN4 link calorie restriction and TOR to Sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol 2007, 5:2330-2341.
16. Dall'Olio F., Vanhooren V., Chen C.C., Slagboom P.E., Wuhrer M., Franceschi C. N-glycomic biomarkers of biological aging and longevity: a link with inflammaging. Ageing Res Rev 2013, 2013(12):685-698.
17. Vanhooren V., Liu X.E., Franceschi C., Gao C.F., Libert C., Contreras R., et al. N-glycan profiles as tools in diagnosis of hepatocellular carcinoma and prediction of healthy human ageing. Mech Ageing Dev 2009, 130:92-97.
18. Cantó C., Auwerx J. AMP-activated protein kinase and its downstream transcriptional pathways. Cell Mol Life Sci 2010, 67:3407-3423.
19. Martin-Montalvo A., Mercken E.M., Mitchell S.J., Palacios H.H., Mote P.L., Scheibye-Knudsen M., et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013, 4:2192.
20. Anisimov V.N. Metformin for ageing and cancer prevention. Aging (Albany NY) 2010, 2:160-174.
21. Onken B., Driscoll M. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS One 2010, 5:e8758.
22. Smith D.L., Elam C.F., Mattison J.A., Lane M.A., Roth G.S., Ingram D.K., et al. Metformin supplementation and life span in Fischer-344 rats. J Gerontol A Biol Sci Med Sci 2010, 65:468-474.
23. Zheng Z., Chen H., Li J., Li T., Zheng B., Zheng Y., et al. Sirtuin 1-mediated cellular metabolic memory of high glucose via the LKB1/AMPK/ROS pathway and therapeutic effects of metformin. Diabetes 2012, 61:217-228.
24. Cantó C., Gerhart-Hines Z., Feige J.N., Lagouge M., Noriega L., Milne J.C., et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009, 458:1056-1060.
25. Caton P.W., Kieswich J., Yaqoob M.M., Holness M.J., Sugden M.C. Metformin opposes impaired AMPK and SIRT1 function and deleterious changes in core clock protein expression in white adipose tissue of genetically-obese db/db mice. Diabetes Obes Metab 2011, 13:1097-1104.
26. Ruderman N.B., Xu X.J., Nelson L., Cacicedo J.M., Saha A.K., Lan F., et al. AMPK and SIRT1: a long-standing partnership?. Am J Physiol Endocrinol Metab 2010, 298:E751-E760.
27. Kitada M., Kume S., Takeda-Watanabe A., Tsuda S., Kanasaki K., Koya D. Calorie restriction in overweight males ameliorates obesity-related alterations and cellular adaptations through anti-aging effects, possibly including AMPK and SIRT1 activation. Biochim Biophys Acta 2013, 1830:4820-4827.
28. Boyle J.G., Logan P.J., Jones G.C., Small M., Sattar N., Connell J.M., et al. AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study. Diabetologia 2011, 54:1799-1809.
29. Rena G., Pearson E.R., Sakamoto K. Molecular mechanism of action of metformin: old or new insights?. Diabetologia 2013, 56:1898-1906.
30. Kimball S.R. Interaction between the AMP-activated protein kinase and mTOR signaling pathways. Med Sci Sports Exerc 2006, 38:1958-1964.
31. Peralba J.M., DeGraffenried L., Friedrichs W., Fulcher L., Gruenwald V., Weiss G., et al. Pharmacodynamic evaluation of CCI-779, an inhibitor of mTOR, in cancer patients. Clin Cancer Res 2003, 9:2887-2892.
32. Selman C., Tullet J.M.A., Wieser D., Irvine E., Lingard S.J., Choudhury A.I., et al. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 2009, 326:140-144.
33. Fenton T.R., Gwalter J., Ericsson J., Gout I.T. Histone acetyltransferases interact with and acetylate p70 ribiosomal S6 kinases invitro and invivo. Int J Biochem Cell Biol 2010, 42:359-366.
34. Sugden M.C., Holness M.J. Metformin, metabolic stress, and mitochondria. Focus on "A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells". Am J Physiol Cell Physiol 2012, 303:C1-C3.
35. Nelson L.E., Valentine R.J., Cacicedo J.M., Gauthier M.S., Ido Y., Ruderman N.B. A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells. Am J Physiol Cell Physiol 2012, 303:C4-C13.
36. Xu X., Hu Y., Zhai X., Lin M., Chen Z., Tian X., et al. Salvianolic acid A preconditioning confers protection against concanavalin A-induced liver injury through SIRT1-mediated repression of p66shc in mice. Toxicol Appl Pharmacol 2013, 273:68-76.
37. Palacios J.A., Herranz D., De Bonis M.L., Velasco S., Serrano M., Blasco M.A. SIRT1 contributes to telomere maintenance and augments global homologous recombination. J Cell Biol 2010, 191:1299-1313.
38. Prescott J., Kraft P., Chasman D.I., Savage S.A., Mirabello L., Berndt S.I., et al. Genome-wide association study of relative telomere length. PLoS One 2011, 6:e19635.
39. Huda N., Tanaka H., Herbert B.S., Reed T., Gilley D. Shared environmental factors associated with telomere length maintenance in elderly male twins. Aging Cell 2007, 6:709-713.
40. Geng F., Shi B.Z., Yuan Y.F., Wu X.Z. The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications. Cell Res 2004, 14:423-433.
41. Shinkawa T., Nakamura K., Yamane N., Shoji-Hosaka E., Kanda Y., Sakurada M., et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 2003, 278:3466-3473.
42. Wang W., Li W., Ikeda Y., Miyagawa J.I., Taniguchi M., Miyoshi E., et al. Ectopic expression of alfa 1,6 fucosyltransferase in mice causes steatosis in the liver and kidney accompanied by a modification of lysosomal acid lipase. Glyco Biol 2011, 11:165-174.
43. Zhao Y., Itoh S., Wang X., Isaji T., Miyoshi E., Kariya Y., et al. Deletion of core fucosylation on α3β1 integrin down-regulates its functions. J Biol Chem 2006, 281:38343-38350.
44. Wang X., Inoue S., Gu J., Miyoshi E., Noda K., Li W., et al. Dysregulation of TGF-b1 receptor activation leads to abnormal lung development and emphysema like phenotype in core fucose deficient mice. Proc Natl Acad Sci USA 2005, 102:15791-15796.
45. Wang X., Gu J., Ihara H., Miyoshi E., Honke K., Taniguchi N. Core fucosylation regulates epidermal growth factor receptor mediated intracellular signaling. J Biol Chem 2006, 281:2572-2577.
46. Nakagawa T., Uozumi N., Nakano M., Mizuno-Horikawa Y., Okuyama N., Taguchi T., et al. Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts. J Biol Chem 2006, 281:29797-29806.
47. Balasubramanyam M., Premanand C., Mohan V. The lymphocyte as a cellular model to study insights into the pathophysiology of diabetes and its complications. Ann N.Y Acad Sci 2002, 958:399-402.
48. Schung T.T., Xu Q., Gao H., Peres-da-Silva A., Draper D.W., Fessler M.B., et al. Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol Cell Biol 2010, 30:4712-4721.