Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging

Aging Cell

Volumn 12, Issue 1, 2013, Pages 102-111

  González Navarro, Herminia ^a   Vinué, Ángela ^b   Sanz, María Jesús ^a,c   Delgado, Mercedes ^d   Pozo, Miguel Angel ^d   Serrano, Manuel ^e   Burks, Deborah J ^f   Andrés, Vicente ^g  

^a Instituto Universitario IVI INCLIVA   (Spain)

^b CSIC   (Spain)

^c UNIVERSITY OF VALENCIA   (Spain)

^d INSTITUTO PLURIDISCIPLINAR   (Spain)

^e Structural Biology and Biocomputing Programme   (Spain)

^f CENTRO DE INVESTIGACIÓN PRÍNCIPE FELIPE   (Spain)

^g CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CNIC   (Spain)

Author keywords

18F fluorodeoxyglucose PET; ARF; CDKN2A; CDKN2B; Diabetes; Insulin resistance; Insulin signaling; P15ink4b; P16ink4a; Pancreatic islet

Indexed keywords

ARF PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 2A; FLUORODEOXYGLUCOSE F 18; GLUCOSE; INSULIN; INSULIN RECEPTOR SUBSTRATE; PHOSPHATIDYLINOSITOL 3 KINASE;

AGING; ANIMAL CELL; APOPTOSIS; ARTICLE; CARBOHYDRATE METABOLISM; CONTROLLED STUDY; CORRELATION ANALYSIS; DISEASE ASSOCIATION; ENZYME ACTIVATION; GENE LOCUS; GENOTYPE; GLUCOSE HOMEOSTASIS; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE TEST; INSULIN RESISTANCE; MACROPHAGE; MOUSE; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTECTION; PROTEIN ANALYSIS; QUANTITATIVE ANALYSIS; SKELETAL MUSCLE; WILD TYPE;

ADP-RIBOSYLATION FACTORS; AGING; ANIMALS; CYCLIN-DEPENDENT KINASE INHIBITOR P16; GENOME-WIDE ASSOCIATION STUDY; GLUCOSE; GLUCOSE INTOLERANCE; INSULIN; INSULIN RESISTANCE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC;

MAMMALIA; MUS;

EID: 84872609955     PISSN: 14749718     EISSN: 14749726     Source Type: Journal    
DOI: 10.1111/acel.12023     Document Type: Article

References (45)

1. Annicotte JS, Blanchet E, Chavey C, Iankova I, Costes S, Assou S, Teyssier J, Dalle S, Sardet C, Fajas L (2009) The CDK4-pRB-E2F1 pathway controls insulin secretion. Nat. Cell Biol. 11, 1017-1023.
2. Baker DJ, Perez-Terzic C, Jin F, Pitel K, Niederlander NJ, Jeganathan K, Yamada S, Reyes S, Rowe L, Hiddinga HJ, Eberhardt NL, Terzic A, van Deursen JM (2008) Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nat. Cell Biol. 10, 825-836.
3. Beckman JA, Creager MA, Libby P (2002) Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 287, 2570-2581.
4. Benetos A, Thomas F, Pannier B, Bean K, Jego B, Guize L (2008) All-cause and cardiovascular mortality using the different definitions of metabolic syndrome. Am. J. Cardiol. 102, 188-191.
5. Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB 3rd, Kaestner KH, Bartolomei MS, Shulman GI, Birnbaum MJ. (2001) Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 292, 1728-1731.
6. Collado M, Blasco MA, Serrano M (2007) Cellular senescence in cancer and aging. Cell 130, 223-233.
7. Consortium TWTCC (2007) Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 447, 661-678.
8. Cunnington MS, Keavney B (2011) Genetic mechanisms mediating atherosclerosis susceptibility at the chromosome 9p21 locus. Curr. Atheroscler. Rep. 13, 193-201.
9. Doria A, Wojcik J, Xu R, Gervino EV, Hauser TH, Johnstone MT, Nolan D, Hu FB, Warram JH (2008) Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes. JAMA 300, 2389-2397.
10. Gan B, Hu J, Jiang S, Liu Y, Sahin E, Zhuang L, Fletcher-Sananikone E, Colla S, Wang YA, Chin L, Depinho RA (2010) Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 468, 701-704.
11. Gil J, Peters G (2006) Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat. Rev. Mol. Cell Biol. 7, 667-677.
12. Gonzalez S, Serrano M (2006) A new mechanism of inactivation of the INK4/ARF locus. Cell Cycle 5, 1382-1384.
13. Gonzalez-Navarro H, Vila-Caballer M, Pastor MF, Vinue A, White MF, Burks D, Andres V (2007) Plasma insulin levels predict the development of atherosclerosis when IRS2 deficiency is combined with severe hypercholesterolemia in apolipoprotein E-null mice. Front. Biosci. 12, 2291-2298.
14. Gonzalez-Navarro H, Vinue A, Vila-Caballer M, Fortuno A, Beloqui O, Zalba G, Burks D, Diez J, Andres V (2008) Molecular mechanisms of atherosclerosis in metabolic syndrome: role of reduced IRS2-dependent signaling. Arterioscler. Thromb. Vasc. Biol. 28, 2187-2194.
15. Gonzalez-Navarro H, Abu Nabah YN, Vinue A, Andres-Manzano MJ, Collado M, Serrano M, Andres V (2010) p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. J. Am. Coll. Cardiol. 55, 2258-2268.
16. Gurumurthy S, Xie SZ, Alagesan B, Kim J, Yusuf RZ, Saez B, Tzatsos A, Ozsolak F, Milos P, Ferrari F, Park PJ, Shirihai OS, Scadden DT, Bardeesy N (2010) The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature 468, 659-663.
17. Hamsten A, Eriksson P (2008) Identifying the susceptibility genes for coronary artery disease: from hyperbole through doubt to cautious optimism. J. Intern. Med. 263, 538-552.
18. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420, 333-336.
19. Hotta K, Kitamoto A, Kitamoto T, Mizusawa S, Teranishi H, So R, Matsuo T, Nakata Y, Hyogo H, Ochi H, Nakamura T, Kamohara S, Miyatake N, Kotani K, Komatsu R, Itoh N, Mineo I, Wada J, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Masuzaki H, Ueno T, Chayama K, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Yoshimatsu H, Sakata T, Tanaka K, Matsuzawa Y, Nakao K, Sekine A (2012) Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography. J. Hum. Genet. 57, 305-310.
20. Hribal ML, Presta I, Procopio T, Marini MA, Stancakova A, Kuusisto J, Andreozzi F, Hammarstedt A, Jansson PA, Grarup N, Hansen T, Walker M, Stefan N, Fritsche A, Haring HU, Pedersen O, Smith U, Laakso M, Sesti G (2011) Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B. Diabetologia 54, 795-802.
21. Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443, 421-426.
22. Kippin TE, Martens DJ, van der Kooy D (2005) p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev. 19, 756-767.
23. Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, Sharpless NE (2004) Ink4a/Arf expression is a biomarker of aging. J. Clin. Investig. 114, 1299-1307.
24. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443, 453-457.
25. Kuo C-L, Murphy AJ, Sayers S, Li R, Yvan-Charvet L, Davis JZ, Krishnamurthy J, Liu Y, Puig O, Sharpless NE, Tall AR, Welch CL (2011) Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation. Arterioscler. Thromb. Vasc. Biol. 31, 2483-2492.
26. Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Mohlke KL, Ibrahim JG, Thomas NE, Sharpless NE (2009) INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PLoS ONE 4, e5027.
27. Matheu A, Pantoja C, Efeyan A, Criado LM, Martin-Caballero J, Flores JM, Klatt P, Serrano M (2004) Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging. Genes Dev. 18, 2736-2746.
28. Matheu A, Maraver A, Klatt P, Flores I, Garcia-Cao I, Borras C, Flores JM, Vina J, Blasco MA, Serrano M (2007) Delayed ageing through damage protection by the Arf/p53 pathway. Nature 448, 375-379.
29. Matheu A, Maraver A, Collado M, Garcia-Cao I, Canamero M, Borras C, Flores JM, Klatt P, Vina J, Serrano M (2009) Anti-aging activity of the Ink4/Arf locus. Aging Cell 8, 152-161.
30. Melzer D, Frayling TM, Murray A, Hurst AJ, Harries LW, Song H, Khaw K, Luben R, Surtees PG, Bandinelli SS, Corsi AM, Ferrucci L, Guralnik JM, Wallace RB, Hattersley AT, Pharoah PD (2007) A common variant of the p16(INK4a) genetic region is associated with physical function in older people. Mech. Ageing Dev. 128, 370-377.
31. Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, Sharpless NE, Morrison SJ (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443, 448-452.
32. Nunn AV, Bell JD, Guy GW (2009) Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe? Nutr. Metab. (Lond) 6, 16.
33. Qian Z, Chen L, Fernald AA, Williams BO, Le Beau MM (2008) A critical role for Apc in hematopoietic stem and progenitor cell survival. J. Exp. Med. 205, 2163-2175.
34. Ressler S, Bartkova J, Niederegger H, Bartek J, Scharffetter-Kochanek K, Jansen-Durr P, Wlaschek M (2006) p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell 5, 379-389.
35. Rhodes CJ (2005) Type 2 diabetes-a matter of beta-cell life and death? Science 307, 380-384.
36. Ruchat SM, Elks CE, Loos RJ, Vohl MC, Weisnagel SJ, Rankinen T, Bouchard C, Perusse L (2009) Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies. Acta Diabetol. 46, 217-226.
37. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Bostrom K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331-1336.
38. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341-1345.
39. Sharpless NE, DePinho RA (2007) How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol. 8, 703-713.
40. Stancakova A, Kuulasmaa T, Paananen J, Jackson AU, Bonnycastle LL, Collins FS, Boehnke M, Kuusisto J, Laakso M (2009) Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5, 327 nondiabetic Finnish men. Diabetes 58, 2129-2136.
41. Vidal A, Koff A (2000) Cell-cycle inhibitors: three families united by a common cause. Gene 247, 1-15.
42. Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391, 900-904.
43. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney AS, McCarthy MI, Hattersley AT (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336-1341.
44. Zhang J, Grindley JC, Yin T, Jayasinghe S, He XC, Ross JT, Haug JS, Rupp D, Porter-Westpfahl KS, Wiedemann LM, Wu H, Li L (2006) PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441, 518-522.
45. Zindy F, Quelle DE, Roussel MF, Sherr CJ (1997) Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene 15, 203-211.