Inflammageing and metaflammation: The yin and yang of type 2 diabetes

Ageing Research Reviews

Volumn 41, Issue , 2018, Pages 1-17

  Prattichizzo, Francesco ^a,b   De Nigris, Valeria ^b   Spiga, Rosangela ^b   Mancuso, Elettra ^b   La Sala, Lucia ^a   Antonicelli, Roberto ^c   Testa, Roberto ^c   Procopio, Antonio Domenico ^c,d   Olivieri, Fabiola ^c,d   Ceriello, Antonio ^a,b,e  

^a IRCCS MULTIMEDICA   (Italy)

^b INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^c INRCA   (Italy)

^d UNIVERSITÀ POLITECNICA DELLE MARCHE   (Italy)

^e INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

Antihyperglycaemic agent; Epigenetic alterations; Fasting regimen; Hyperglycaemic memory; Immune system; Immunometabolism; Inflammageing; Mediterranean diet; Metaflammation; Microbiota; microRNA; Oxidative stress; SASP; Senescence; Type 2 diabetes

Indexed keywords

CHOLESTEROL; EMPAGLIFLOZIN; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOSE; LIPID; METFORMIN; MICRORNA; PATTERN RECOGNITION RECEPTOR; SATURATED FATTY ACID;

AGING; CELL AGING; DIET; DNA METHYLATION; ENDOTOXEMIA; EPIGENETICS; EXERCISE; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; GLUCOSE INTAKE; HISTONE ACETYLATION; HISTONE METHYLATION; HUMAN; HYPERGLYCEMIA; HYPOTHALAMUS; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; INFLAMMATION; INSULIN BLOOD LEVEL; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; LIPID DIET; METABOLISM; MICROFLORA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PATHOLOGY; PHYSICAL ACTIVITY; REVIEW; ANIMAL; CARDIOVASCULAR SYSTEM; DIET THERAPY; IMMUNOLOGY; OXIDATIVE STRESS; PHYSIOLOGY; PROCEDURES; TRENDS;

ANIMALS; CARDIOVASCULAR SYSTEM; CELLULAR SENESCENCE; DIABETES MELLITUS, TYPE 2; DIET THERAPY; EXERCISE; HUMANS; INFLAMMATION; OXIDATIVE STRESS;

EID: 85032443928     PISSN: 15681637     EISSN: 18729649     Source Type: Journal    
DOI: 10.1016/j.arr.2017.10.003     Document Type: Review

References (261)

1. Abdelmagid, S.A., Clarke, S.E., Nielsen, D.E., Badawi, A., El-Sohemy, A., Mutch, D.M., Ma, D.W., Comprehensive profiling of plasma fatty acid concentrations in young healthy Canadian adults. PLoS One, 10(February (2)), 2015, e0116195, 10.1371/journal.pone.0116195 (eCollection 2015).
2. Acosta, J.C., Banito, A., Wuestefeld, T., Georgilis, A., Janich, P., Morton, J.P., Athineos, D., Kang, T.W., Lasitschka, F., Andrulis, M., Pascual, G., Morris, K.J., Khan, S., Jin, H., Dharmalingam, G., Snijders, A.P., Carroll, T., Capper, D., Pritchard, C., Inman, G.J., Longerich, T., Sansom, O.J., Benitah, S.A., Zender, L., Gil, J., A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15:August (8) (2013), 978–990, 10.1038/ncb2784.
3. Aguayo-Mazzucato, C., van Haaren, M., Mruk, M., Lee, T.B. Jr., Crawford, C., Hollister-Lock, J., Sullivan, B.A., Johnson, J.W., Ebrahimi, A., Dreyfuss, J.M., Van Deursen, J., Weir, G.C., Bonner-Weir, S., Cell ageing markers have heterogeneous distribution and are induced by insulin resistance. Cell Metab. 25:April (4) (2017), 898–910, 10.1016/j.cmet.2017.03.015 (e5).
4. Arruda, A.P., Milanski, M., Coope, A., Torsoni, A.S., Ropelle, E., Carvalho, D.P., Carvalheira, J.B., Velloso, L.A., Low-grade hypothalamic inflammation leads to defective thermogenesis, insulin resistance, and impaired insulin secretion. Endocrinology 152:April (4) (2011), 1314–1326, 10.1210/en.2010-0659 (Epub 2011 Jan 25).
5. Bai, Y., Wang, X., Zhao, S., Ma, C., Cui, J., Zheng, Y., Sulforaphane protects against cardiovascular disease via Nrf2 activation. Oxid. Med. Cell. Longev., 2015, 2015, 407580, 10.1155/2015/407580 (Epub 2015 Oct 25. Review.).
6. Baker, D.J., Childs, B.G., Durik, M., Wijers, M.E., Sieben, C.J., Zhong, J., Saltness, R.A., Jeganathan, K.B., Verzosa, G.C., Pezeshki, A., Khazaie, K., Miller, J.D., van Deursen, J.M., Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530:February (7589) (2016), 184–189, 10.1038/nature16932.
7. Bannister, C.A., Holden, S.E., Jenkins-Jones, S., Morgan, C.L., Halcox, J.P., Schernthaner, G., Mukherjee, J., Currie, C.J., Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes. Metab. 16:November (11) (2014), 1165–1173, 10.1111/dom.12354 (Epub 2014 Jul 31).
8. Baraibar, M.A., Hyzewicz, J., Rogowska-Wrzesinska, A., Bulteau, A.L., Prip-Buus, C., Butler-Browne, G., Friguet, B., Impaired energy metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes. Ageing (Albany N. Y.) 8:December (12) (2016), 3375–3389, 10.18632/ageing.101126.
9. Barnosky, A.R., Hoddy, K.K., Unterman, T.G., Varady, K.A., Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings. Transl. Res. 164:October (4) (2014), 302–311, 10.1016/j.trsl.2014.05.013.
10. Barzilai, N., Crandall, J.P., Kritchevsky, S.B., Espeland, M.A., Metformin as a tool to target ageing. Cell Metab. 23:June (6) (2016), 1060–1065, 10.1016/j.cmet.2016.05.011.
11. Baur, J.A., Pearson, K.J., Price, N.L., Jamieson, H.A., Lerin, C., Kalra, A., Prabhu, V.V., Allard, J.S., Lopez-Lluch, G., Lewis, K., Pistell, P.J., Poosala, S., Becker, K.G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K.W., Spencer, R.G., Lakatta, E.G., Le Couteur, D., Shaw, R.J., Navas, P., Puigserver, P., Ingram, D.K., de Cabo, R., Sinclair, D.A., Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:November (7117) (2006), 337–342.
12. Berry, D.C., Jiang, Y., Arpke, R.W., Close, E.L., Uchida, A., Reading, D., Berglund, E.D., Kyba, M., Graff, J.M., Cellular ageing contributes to failure of cold-induced beige adipocyte formation in old mice and humans. Cell Metab. 25:January (1) (2017), 166–181, 10.1016/j.cmet.2016.10.023.
13. Biagi, E., Franceschi, C., Rampelli, S., Severgnini, M., Ostan, R., Turroni, S., Consolandi, C., Quercia, S., Scurti, M., Monti, D., Capri, M., Brigidi, P., Candela, M., Gut microbiota and extreme longevity. Curr. Biol. 26:June (11) (2016), 1480–1485, 10.1016/j.cub.2016.04.016.
14. Biswas, S.K., Mantovani, A., Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11 (2010), 889–896.
15. Bjelakovic, G., Nikolova, D., Gluud, C., Antioxidant supplements to prevent mortality. JAMA 310:September (11) (2013), 1178–1179, 10.1001/jama.2013.277028.
16. Blüher, M., Kahn, B.B., Kahn, C.R., Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:January (5606) (2003), 572–574.
17. Blagosklonny, M.V., Calorie restriction: decelerating mTOR-driven ageing from cells to organisms (including humans). Cell Cycle 9:February (4) (2010), 683–688.
18. Blagosklonny, M.V., Rapamycin extends life- and health span because it slows ageing. Ageing (Albany N. Y.) 5:August (8) (2013), 592–598.
19. Boccardi, V., Paolisso, G., Mecocci, P., Nutrition and lifestyle in healthy ageing: the telomerase challenge. Ageing (Albany N. Y.) 8:January (1) (2016), 12–15.
20. Bonfigli, A.R., Spazzafumo, L., Prattichizzo, F., Bonafè, M., Mensà, E., Micolucci, L., Giuliani, A., Fabbietti, P., Testa, R., Boemi, M., Lattanzio, F., Olivieri, F., Leukocyte telomere length and mortality risk in patients with type 2 diabetes. Oncotarget 7:August (32) (2016), 50835–50844, 10.18632/oncotarget.10615.
21. Bonomini, F., Rodella, L.F., Rezzani, R., Metabolic syndrome, ageing and involvement of oxidative stress. Ageing Dis. 6:2 (2015), 109–120.
22. Bułdak, Ł., Machnik, G., Bułdak, R.J., Łabuzek, K., Bołdys, A., Belowski, D., Basiak, M., Okopień, B., Exenatide (a GLP-1 agonist) expresses anti-inflammatory properties in cultured human monocytes/macrophages in a protein kinase A and B/Akt manner. Pharmacol. Rep. 68:April (2) (2016), 329–337, 10.1016/j.pharep.2015.10.008.
23. Calabrese, E.J., Hormesis: a revolution in toxicology, risk assessment and medicine. EMBO Rep., 5(October), 2004 (Spec No:S37-40.).
24. Calder, P.C., Dimitriadis, G., Newsholme, P., Glucose metabolism in lymphoid and inflammatory cells and tissues. Curr. Opin. Clin. Nutr. Metab. Care 10:July (4) (2007), 531–540 (Review).
25. Camandola, S., Mattson, M.P., Toll-like receptor 4 mediates fat, sugar, and umami taste preference and food intake and body weight regulation. Obesity (Silver Spring) 25:July (7) (2017), 1237–1245, 10.1002/oby.21871 (Epub 2017 May 12).
26. Cameron, A.R., Morrison, V.L., Levin, D., Mohan, M., Forteath, C., Beall, C., McNeilly, A.D., Balfour, D.J., Savinko, T., Wong, A.K., Viollet, B., Sakamoto, K., Fagerholm, S.C., Foretz, M., Lang, C.C., Rena, G., Anti-inflammatory effects of metformin irrespective of diabetes status. Circ. Res. 119:August (5) (2016), 652–665, 10.1161/CIRCRESAHA.116.308445 (Epub 2016 Jul 14).
27. Campbell, J.M., Bellman, S.M., Stephenson, M.D., Lisy, K., Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. Ageing Res. Rev. 10:August (40) (2017), 31–44, 10.1016/j.arr.2017.08.003.
28. Cani, P.D., Knauf, C., Iglesias, M.A., Drucker, D.J., Delzenne, N.M., Burcelin, R., Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes 55:May (5) (2006), 1484–1490.
29. Cani, P.D., Neyrinck, A.M., Fava, F., Knauf, C., Burcelin, R.G., Tuohy, K.M., Gibson, G.R., Delzenne, N.M., Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 50:November (11) (2007), 2374–2383.
30. Cani, P.D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A.M., Delzenne, N.M., Burcelin, R., Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57:June (6) (2008), 1470–1481, 10.2337/db07-1403 (Epub 2008 Feb 27).
31. Cani, P.D., Osto, M., Geurts, L., Everard, A., Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 3:July–August (4) (2012), 279–288 (Epub 2012 May 14).
32. Ceriello, A., Testa, R., Antioxidant anti-inflammatory treatment in type 2 diabetes. Diabetes Care 32:Supplement 2 (2009), S232–S236.
33. Ceriello, A., Novials, A., Ortega, E., Canivell, S., La Sala, L., Pujadas, G., Esposito, K., Giugliano, D., Genovese, S., Glucagon-like peptide 1 reduces endothelial dysfunction, inflammation, and oxidative stress induced by both hyperglycaemia and hypoglycaemia in type 1 diabetes. Diabetes Care 36:August (8) (2013), 2346–2350, 10.2337/dc12-2469.
34. Ceriello, A., The emerging challenge in diabetes: the metabolic memory. Vasc. Pharmacol. 57 (2012), 133–138.
35. Chen, J., Brodsky, S.V., Goligorsky, D.M., Hampel, D.J., Li, H., Gross, S.S., Goligorsky, M.S., Glycated collagen I induces premature senescence-like phenotypic changes in endothelial cells. Circ. Res. 90:June (12) (2002), 1290–1298.
36. Chen, H., Ruiz, P.D., McKimpson, W.M., Novikov, L., Kitsis, R.N., Gamble, M.J., MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype. Mol. Cell 59:September (5) (2015), 719–731, 10.1016/j.molcel.2015.07.011.
37. Cheng, R., Ma, J.X., Angiogenesis in diabetes and obesity. Rev. Endocr. Metab. Disord. 16:March (1) (2015), 67–75, 10.1007/s11154-015-9310-7 (Review).
38. Cheng, C.W., Villani, V., Buono, R., Wei, M., Kumar, S., Yilmaz, O.H., Cohen, P., Sneddon, J.B., Perin, L., Longo, V.D., Fasting-mimicking diet promotes Ngn3-driven β-cell regeneration to reverse diabetes. Cell 168:February (5) (2017), 775–788, 10.1016/j.cell.2017.01.040 (e12).
39. Childs, B.G., Baker, D.J., Kirkland, J.L., Campisi, J., van Deursen, J.M., Senescence and apoptosis: dueling or complementary cell fates?. EMBO Rep. 15:November (11) (2014), 1139–1153, 10.15252/embr.201439245 (Review).
40. Childs, B.G., Durik, M., Baker, D.J., van Deursen, J.M., Cellular senescence in ageing and age-related disease: from mechanisms to therapy. Nat. Med. 21:December (12) (2015), 1424–1435, 10.1038/nm.4000 (Review).
41. Childs, B.G., Baker, D.J., Wijshake, T., Conover, C.A., Campisi, J., van Deursen, J.M., Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 354:October (6311) (2016), 472–477 (Epub 2016 Oct 27).
42. Choi, I.Y., Piccio, L., Childress, P., Bollman, B., Ghosh, A., Brandhorst, S., Suarez, J., Michalsen, A., Cross, A.H., Morgan, T.E., Wei, M., Paul, F., Bock, M., Longo, V.D., A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep. 15:June (10) (2016), 2136–2146, 10.1016/j.celrep.2016.05.009.
43. Chudyk, A., Petrella, R.J., Effects of exercise on cardiovascular risk factors in type 2 diabetes: a meta-analysis. Diabetes Care 34:May (5) (2011), 1228–1237, 10.2337/dc10-1881 (Review).
44. Coppé, J.P., Rodier, F., Patil, C.K., Freund, A., Desprez, P.Y., Campisi, J., Tumor suppressor and ageing biomarker p16(INK4a) induces cellular senescence without the associated inflammatory secretory phenotype. J. Biol. Chem. 286:October (42) (2011), 36396–36403, 10.1074/jbc.M111.257071 (Epub 2011 Aug 31).
45. Costantino, S., Paneni, F., Battista, R., Castello, L., Capretti, G., Chiandotto, S., Tanese, L., Russo, G., Pitocco, D., Lanza, G.A., Volpe, M., Lüscher, T.F., Cosentino, F., Impact of glycemic variability on chromatin remodeling, oxidative stress, and endothelial dysfunction in patients with type 2 diabetes and with target HbA1c levels. Diabetes 66:September (9) (2017), 2472–2482, 10.2337/db17-0294 (Epub 2017 Jun 20).
46. Cui, W., Bai, Y., Miao, X., Luo, P., Chen, Q., Tan, Y., Rane, M.J., Miao, L., Cai, L., Prevention of diabetic nephropathy by sulforaphane: possible role of Nrf2 upregulation and activation. Oxid. Med. Cell. Longev., 2012, 2012, 821936, 10.1155/2012/821936.
47. Dörr, J.R., Yu, Y., Milanovic, M., Beuster, G., Zasada, C., Däbritz, J.H., Lisec, J., Lenze, D., Gerhardt, A., Schleicher, K., Kratzat, S., Purfürst, B., Walenta, S., Mueller-Klieser, W., Gräler, M., Hummel, M., Keller, U., Buck, A.K., Dörken, B., Willmitzer, L., Reimann, M., Kempa, S., Lee, S., Schmitt, C.A., Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 501:September (7467) (2013), 421–425, 10.1038/nature12437.
48. Danesh, J., Kaptoge, S., Mann, A.G., Sarwar, N., Wood, A., Angleman, S.B., Wensley, F., Higgins, J.P., Lennon, L., Eiriksdottir, G., Rumley, A., Whincup, P.H., Lowe, G.D., Gudnason, V., Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med., 5(April (4)), 2008, e78, 10.1371/journal.pmed.0050078 (Review).
49. Daniele, G., Guardado Mendoza, R., Winnier, D., Fiorentino, T.V., Pengou, Z., Cornell, J., Andreozzi, F., Jenkinson, C., Cersosimo, E., Federici, M., Tripathy, D., Folli, F., The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol. 51:February (1) (2014), 123–131.
50. Dasu, M.R., Ramirez, S., Isseroff, R.R., Toll-like receptors and diabetes: a therapeutic perspective. Clin. Sci. (Lond.) 122:March (5) (2012), 203–214, 10.1042/CS20110357 (Review).
51. De Souza, C.T., Araujo, E.P., Bordin, S., Ashimine, R., Zollner, R.L., Boschero, A.C., Saad, M.J., Velloso, L.A., Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146:October (10) (2005), 4192–4199 (Epub 2005 Jul 7).
52. Di Dalmazi, G., Pagotto, U., Pasquali, R., Vicennati, V., Glucocorticoids and type 2 diabetes: from physiology to pathology. J. Nutr. Metab., 2012, 2012, 525093, 10.1155/2012/525093 (Epub 2012 Dec 18).
53. Donath, M.Y., Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat. Rev. Drug Discov. 13:6 (2014), 465–476.
54. Donohoe, D.R., Garge, N., Zhang, X., Sun, W., O'Connell, T.M., Bunger, M.K., Bultman, S.J., The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 13:May (5) (2011), 517–526, 10.1016/j.cmet.2011.02.018.
55. Dostert, C., Pétrilli, V., Van Bruggen, R., Steele, C., Mossman, B.T., Tschopp, J., Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320:May (5876) (2008), 674–677, 10.1126/science.1156995.
56. Dror, E., Dalmas, E., Meier, D.T., Wueest, S., Thévenet, J., Thienel, C., Timper, K., Nordmann, T.M., Traub, S., Schulze, F., Item, F., Vallois, D., Pattou, F., Kerr-Conte, J., Lavallard, V., Berney, T., Thorens, B., Konrad, D., Böni-Schnetzler, M., Donath, M.Y., Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat. Immunol. 18:March (3) (2017), 283–292, 10.1038/ni.3659 (Epub 2017 Jan 16).
57. Drucker, D.J., The cardiovascular biology of glucagon-like peptide-1. Cell Metab. 24:July (1) (2016), 15–30, 10.1016/j.cmet.2016.06.009 (Review).
58. Duewell, P., Kono, H., Rayner, K.J., Sirois, C.M., Vladimer, G., Bauernfeind, F.G., Abela, G.S., Franchi, L., Nuñez, G., Schnurr, M., Espevik, T., Lien, E., Fitzgerald, K.A., Rock, K.L., Moore, K.J., Wright, S.D., Hornung, V., Latz, E., NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:April (7293) (2010), 1357–1361, 10.1038/nature08938.
59. Ehses, J.A., Perren, A., Eppler, E., et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56 (2007), 2356–2370.
60. El-Mir, M.Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., Leverve, X., Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J. Biol. Chem. 275:January (1) (2000), 223–228.
61. El-Osta, A., Redox mediating epigenetic changes confer metabolic memories. Circ. Res. 111:July (3) (2012), 262–264, 10.1161/CIRCRESAHA.112.274936.
62. Ernst, I.M., Pallauf, K., Bendall, J.K., Paulsen, L., Nikolai, S., Huebbe, P., Roeder, T., Rimbach, G., Vitamin E supplementation and lifespan in model organisms. Ageing Res. Rev. 12:January (1) (2013), 365–375, 10.1016/j.arr.2012.10.002 (Review).
63. Esposito, K., Giugliano, D., Mediterranean diet and type 2 diabetes. Diabetes Metab. Res. Rev. 30:March (Suppl. 1) (2014), 34–40, 10.1002/dmrr.2516 (Review).
64. Esposito, K., Nappo, F., Marfella, R., Giugliano, G., Giugliano, F., Ciotola, M., Quagliaro, L., Ceriello, A., Giugliano, D., Inflammatory cytokine concentrations are acutely increased by hyperglycaemia in humans: role of oxidative stress. Circulation 106:October (16) (2002), 2067–2072.
65. Esposito, K., Nappo, F., Giugliano, F., Di Palo, C., Ciotola, M., Barbieri, M., Paolisso, G., Giugliano, D., Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus. Am. J. Clin. Nutr. 78:December (6) (2003), 1135–1140.
66. Estruch, R., Ros, E., Salas-Salvadó, J., Covas, M.I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., Lamuela-Raventos, R.M., Serra-Majem, L., Pintó, X., Basora, J., Muñoz, M.A., Sorlí, J.V., Martínez, J.A., Martínez-González, M.A., PREDIMED Study Investigators, Primary prevention of cardiovascular disease with a Mediterranean diet. N. Engl. J. Med. 368:April (14) (2013), 1279–1290, 10.1056/NEJMoa1200303.
67. Forouzandeh, F., Salazar, G., Patrushev, N., Xiong, S., Hilenski, L., Fei, B., Alexander, R.W., Metformin beyond diabetes: pleiotropic benefits of metformin in attenuation of atherosclerosis. J. Am. Heart Assoc., 3(December (6)), 2014, e001202, 10.1161/JAHA.114.001202.
68. Forslund, K., Hildebrand, F., Nielsen, T., Falony, G., Le Chatelier, E., Sunagawa, S., Prifti, E., Vieira-Silva, S., Gudmundsdottir, V., Krogh Pedersen, H., Arumugam, M., Kristiansen, K., Voigt, A.Y., Vestergaard, H., Hercog, R., Igor Costea, P., Kultima, J.R., Li, J., Jørgensen, T., Levenez, F., Dore, J., Meta consortium, H.I.T., Nielsen, H.B., Brunak, S., Raes, J., Hansen, T., Wang, J., Ehrlich, S.D., Bork, P., Pedersen, O., Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528:December (7581) (2015), 262–266, 10.1038/nature15766 (Epub 2015 Dec 2).
69. Franceschi, C., Bonafè, M., Valensin, S., Olivieri, F., De Luca, M., Ottaviani, E., De Benedictis, G., Inflamm-ageing. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908:June (2000), 244–254 (Review).
70. Franceschi, C., Garagnani, P., Vitale, G., Capri, M., Salvioli, S., Inflammageing and ‘Garb-ageing’. Trends Endocrinol. Metab. 28:March (3) (2017), 199–212, 10.1016/j.tem.2016.09.005 (Epub 2016 Oct 24. Review).
71. Franceschi, C., Healthy ageing in 2016: obesity in geroscience—is cellular senescence the culprit?. Nat. Rev. Endocrinol. 13:February (2) (2017), 76–78, 10.1038/nrendo.2016.213 (Epub 2017 Jan 6).
72. Freund, A., Patil, C.K., Campisi, J., p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 30:April (8) (2011), 1536–1548, 10.1038/emboj.2011.69.
73. Fried, S.K., Bunkin, D.A., Greenberg, A.S., Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 83 (1998), 847–850.
74. Fumagalli, M., d'Adda di Fagagna, F., ASPense and DDRama in cancer and ageing. Nat. Cell Biol. 11:August (8) (2009), 921–923, 10.1038/ncb0809-921.
75. Gallagher, K.A., Joshi, A., Carson, W.F., Schaller, M., Allen, R., Mukerjee, S., Kittan, N., Feldman, E.L., Henke, P.K., Hogaboam, C., Burant, C.F., Kunkel, S.L., Epigenetic changes in bone marrow progenitor cells influence the inflammatory phenotype and alter wound healing in type 2 diabetes. Diabetes 64:April (4) (2015), 1420–1430, 10.2337/db14-0872 (Epub 2014 Nov 3).
76. Galván-Peña, S., O'Neill, L.A., Metabolic reprograming in macrophage polarization. Front. Immunol., 2(September (5)), 2014, 420, 10.3389/fimmu.2014.00420 (eCollection 2014. Review.).
77. Gao, Y., Bielohuby, M., Fleming, T., Grabner, G.F., Foppen, E., Bernhard, W., Guzmán-Ruiz, M., Layritz, C., Legutko, B., Zinser, E., García-Cáceres, C., Buijs, R.M., Woods, S.C., Kalsbeek, A., Seeley, R.J., Nawroth, P.P., Bidlingmaier, M., Tschöp, M.H., Yi, C.X., Dietary sugars, not lipids, drive hypothalamic inflammation. Mol. Metab. 6:June (8) (2017), 897–908.
78. Gardner, S.E., Humphry, M., Bennett, M.R., Clarke, M.C., Senescent vascular smooth muscle cells drive inflammation through an interleukin-1α-dependent senescence-associated secretory phenotype. Arterioscler. Thromb. Vasc. Biol. 35:September (9) (2015), 1963–1974, 10.1161/ATVBAHA.115.305896 (Epub 2015 Jul 2).
79. Garg, S.K., Delaney, C., Shi, H., Yung, R., Changes in adipose tissue macrophages and T cells during ageing. Crit. Rev. Immunol. 34 (2014), 1–14.
80. Geerlings, S.E., Hoepelman, A.I., Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol. Med. Microbiol. 26:December (3–4) (1999), 259–265 (Review).
81. Geiger, A., Walker, A., Nissen, E., Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice. Biochem. Biophys. Res. Commun. 467 (2015), 303–309.
82. Gijsbers, L., Ding, E.L., Malik, V.S., de Goede, J., Geleijnse, J.M., Soedamah-Muthu, S.S., Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies. Am. J. Clin. Nutr. 103:April (4) (2016), 1111–1124, 10.3945/ajcn.115.123216 (Epub 2016 Feb 24. Review).
83. Gil-Cardoso, K., Ginés, I., Pinent, M., Ardévol, A., Blay, M., Terra, X., Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity. Nutr. Res. Rev. 29:December (2) (2016), 234–248.
84. Giugliano, D., Ceriello, A., Esposito, K., The effects of diet on inflammation: emphasis on the metabolic syndrome. J. Am. Coll. Cardiol. 48:August (4) (2006), 677–685 (Review).
85. Glass, C.K., Olefsky, J.M., Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab. 15:May (5) (2012), 635–645, 10.1016/j.cmet.2012.04.001 (Review).
86. González-Navarro, H., Vinué, Á, Sanz, M.J., Delgado, M., Pozo, M.A., Serrano, M., Burks, D.J., Andrés, V., Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with ageing. Ageing Cell 12:February (1) (2013), 102–111, 10.1111/acel.12023 (Epub 2012 Dec 5).
87. Grasset, E., Puel, A., Charpentier, J., Collet, X., Christensen, J.E., Tercé, F., Burcelin, R., A specific gut microbiota dysbiosis of type 2 diabetic mice induces GLP-1 resistance through an enteric NO-dependent and gut-brain axis mechanism. Cell Metab. 25:May (5) (2017), 1075–1090, 10.1016/j.cmet.2017.04.013 (e5).
88. Gruver, A.L., Hudson, L.L., Sempowski, G.D., Immunosenescence of ageing. J. Pathol. 211:January (2) (2007), 144–156 (Review).
89. Guo, H., Callaway, J.B., Ting, J.P., Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med. 21:July (7) (2015), 677–687, 10.1038/nm.3893 (Review).
90. Hadjiyanni, I., Siminovitch, K.A., Danska, J.S., Drucker, D.J., Glucagon-like peptide-1 receptor signalling selectively regulates murine lymphocyte proliferation and maintenance of peripheral regulatory T cells. Diabetologia 53:April (4) (2010), 730–740.
91. Halicka, H.D., Zhao, H., Li, J., Traganos, F., Zhang, S., Lee, M., Darzynkiewicz, Z., Genome protective effect of metformin as revealed by reduced level of constitutive DNA damage signaling. Ageing (Albany N. Y.) 3:October (10) (2011), 1028–1038.
92. Hall, B.M., Balan, V., Gleiberman, A.S., Strom, E., Krasnov, P., Virtuoso, L.P., Rydkina, E., Vujcic, S., Balan, K., Gitlin, I., Leonova, K., Polinsky, A., Chernova, O.B., Gudkov, A.V., Ageing of mice is associated with p16(Ink4a)- and β-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells. Ageing (Albany N. Y.) 8:July (7) (2016), 1294–1315, 10.18632/ageing.100991.
93. Halliwell, B., Rafter, J., Jenner, A., Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not?. Am. J. Clin. Nutr. 81:January (Suppl. 1) (2005), 268S–276S (Review).
94. Han, B., Sivaramakrishnan, P., Lin, C.J., Neve, I.A.A., He, J., Tay, L.W.R., Sowa, J.N., Sizovs, A., Du, G., Wang, J., Herman, C., Wang, M.C., Microbial genetic composition tunes host longevity. Cell 169:June (7) (2017), 1249–1262, 10.1016/j.cell.2017.05.036 (e13).
95. Handschin, C., Spiegelman, B.M., The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 454:July (7203) (2008), 463–469, 10.1038/nature07206 (Review).
96. Harris, T.B., Ferrucci, L., Tracy, R.P., Corti, M.C., Wacholder, S., Ettinger, W.H. Jr., Heimovitz, H., Cohen, H.J., Wallace, R., Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am. J. Med. 106:May (5) (1999), 506–512.
97. Harvie, M.N., Pegington, M., Mattson, M.P., Frystyk, J., Dillon, B., Evans, G., Cuzick, J., Jebb, S.A., Martin, B., Cutler, R.G., Son, T.G., Maudsley, S., Carlson, O.D., Egan, J.M., Flyvbjerg, A., Howell, A., The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int. J. Obes. (Lond.) 35:May (5) (2011), 714–727, 10.1038/ijo.2010.171.
98. Hasan, A.U., Ohmori, K., Hashimoto, T., Kamitori, K., Yamaguchi, F., Konishi, K., Noma, T., Igarashi, J., Yamashita, T., Hirano, K., Tokuda, M., Minamino, T., Nishiyama, A., Kohno, M., Increase in tumor suppressor Arf compensates gene dysregulation in vitro aged adipocytes. Biogerontology 18:February (1) (2017), 55–68, 10.1007/s10522-016-9661-9 (Epub 2016 Oct 12).
99. Haschemi, A., Kosma, P., Gille, L., Evans, C.R., Burant, C.F., Starkl, P., Knapp, B., Haas, R., Schmid, J.A., Jandl, C., Amir, S., Lubec, G., Park, J., Esterbauer, H., Bilban, M., Brizuela, L., Pospisilik, J.A., Otterbein, L.E., Wagner, O., The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15:June (6) (2012), 813–826, 10.1016/j.cmet.2012.04.023.
100. Hayakawa, T., Iwai, M., Aoki, S., Takimoto, K., Maruyama, M., Maruyama, W., Motoyama, N., SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. PLoS One, 10(January (1)), 2015, e0116480, 10.1371/journal.pone.0116480.
101. Heilmeier, U., Hackl, M., Skalicky, S., Weilner, S., Schroeder, F., Vierlinger, K., Patsch, J.M., Baum, T., Oberbauer, E., Lobach, I., Burghardt, A.J., Schwartz, A.V., Grillari, J., Link, T.M., Serum miRNA signatures are indicative of skeletal fractures in postmenopausal women with and without type 2 diabetes and influence osteogenic and adipogenic differentiation of adipose tissue-derived mesenchymal stem cells in vitro. J. Bone Miner. Res. 31:December (12) (2016), 2173–2192, 10.1002/jbmr.2897 (Epub 2016 Sep 26).
102. Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R.Z., Nevo, Y., Fixler, Y., Shreibman, D., Zamir, A., Tornovsky-Babeay, S., Dai, C., Glaser, B., Powers, A.C., Shapiro, A.M., Magnuson, M.A., Dor, Y., Ben-Porath, I., p16(Ink4a)-induced senescence of pancreatic beta cells enhances insulin secretion. Nat. Med. 22:April (4) (2016), 412–420, 10.1038/nm.4054.
103. Herder, C., Haastert, B., Müller-Scholze, S., Koenig, W., Thorand, B., Holle, R., Wichmann, H.E., Scherbaum, W.A., Martin, S., Kolb, H., Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes 54:December (Suppl. 2) (2005), S11–S17.
104. Hogan, A.E., Gaoatswe, G., Lynch, L., Corrigan, M.A., Woods, C., O'Connell, J., O'Shea, D., Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus. Diabetologia 57:April (4) (2014), 781–784, 10.1007/s00125-013-3145-0.
105. Holloszy, J.O., Fontana, L., Caloric restriction in humans. Exp. Gerontol. 42:August (8) (2007), 709–712 (Epub 2007 Mar 31. Review).
106. Holman, R.R., Sourij, H., Califf, R.M., Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2 diabetes. Lancet 383:June (9933) (2014), 2008–2017, 10.1016/S0140-6736(14)60794-7 (Review).
107. Hong, S., Mannan, A.M., Inoki, K., Evaluation of the nutrient-sensing mTOR pathway. Methods Mol. Biol. 821 (2012), 29–44, 10.1007/978-1-61779-430-8_3.
108. Horvath, S., Erhart, W., Brosch, M., Ammerpohl, O., von Schoenfels, W., Ahrens, M., Heits, N., Bell, J.T., Tsai, P.C., Spector, T.D., Deloukas, P., Siebert, R., Sipos, B., Becker, T., Roecken, C., Schafmayer, C., Hampe, J., Obesity accelerates epigenetic aging of human liver. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 15538–15543.
109. Horvath, T.L., The hardship of obesity: a soft-wired hypothalamus. Nat. Neurosci. 8:May (5) (2005), 561–565 (Review).
110. Horvath, S., DNA methylation age of human tissues and cell types. Genome Biol., 14(10), 2013, R115.
111. Hotamisligil, G.S., Erbay, E., Nutrient sensing and inflammation in metabolic diseases. Nat. Rev. Immunol. 8:December (12) (2008), 923–934, 10.1038/nri2449.
112. Hotamisligil, G.S., Shargill, N.S., Spiegelman, B.M., Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:January (5091) (1993), 87–91.
113. Hotamisligil, G.S., Peraldi, P., Budavari, A., Ellis, R., White, M.F., Spiegelman, B.M., IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271:February (5249) (1996), 665–668.
114. Hotamisligil, G.S., Inflammation and metabolic disorders. Nature 444:December (7121) (2006), 860–867 (Review).
115. Hotamisligil, G.S., Inflammation, metaflammation and immunometabolic disorders. Nature 542:February (7640) (2017), 177–185, 10.1038/nature21363.
116. Howitz, K.T., Sinclair, D.A., Xenohormesis: sensing the chemical cues of other species. Cell 133:May (3) (2008), 387–391, 10.1016/j.cell.2008.04.019.
117. Huang, S., Rutkowsky, J.M., Snodgrass, R.G., Ono-Moore, K.D., Schneider, D.A., Newman, J.W., Adams, S.H., Hwang, D.H., Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. J. Lipid Res. 53:September (9) (2012), 2002–2013, 10.1194/jlr.D029546.
118. Hubbard, B.P., Sinclair, D.A., Small molecule SIRT1 activators for the treatment of ageing and age-related diseases. Trends Pharmacol. Sci. 35:March (3) (2014), 146–154, 10.1016/j.tips.2013.12.004 (Review).
119. Jia, Y., Zheng, Z., Wang, Y., Zhou, Q., Cai, W., Jia, W., Yang, L., Dong, M., Zhu, X., Su, L., Hu, D., SIRT1 is a regulator in high glucose-induced inflammatory response in RAW264.7 cells. PLoS One, 10(March (3)), 2015, e0120849, 10.1371/journal.pone.0120849.
120. Johnson, A.R., Milner, J.J., Makowski, L., The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol. Rev. 249:September (1) (2012), 218–238, 10.1111/j.1600-065X.2012.01151.x (Review).
121. Kahles, F., Meyer, C., Möllmann, J., Diebold, S., Findeisen, H.M., Lebherz, C., Trautwein, C., Koch, A., Tacke, F., Marx, N., Lehrke, M., GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering. Diabetes 63:October (10) (2014), 3221–3229, 10.2337/db14-0100.
122. Kahn, C.R., White, M.F., The insulin receptor and the molecular mechanism of insulin action. J. Clin. Invest. 82:October (4) (1988), 1151–1156.
123. Kakkar, R., Mantha, S.V., Kalra, J., Prasad, K., Time course study of oxidative stress in aorta and heart of diabetic rat. Clin. Sci. (Lond.) 91:October (4) (1996), 441–448.
124. Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R., Kitazawa, S., Miyachi, H., Maeda, S., Egashira, K., Kasuga, M., MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116:June (6) (2006), 1494–1505 (Epub 2006 May 11).
125. Kapeta, S., Chondrogianni, N., Gonos, E.S., Nuclear erythroid factor 2-mediated proteasome activation delays senescence in human fibroblasts. J. Biol. Chem. 285:March (11) (2010), 8171–8184, 10.1074/jbc.M109.031575.
126. Kim, K.A., Jeong, J.J., Yoo, S.Y., Kim, D.H., Gut microbiota lipopolysaccharide accelerates inflamm-ageing in mice. BMC Microbiol., 16(January (9)), 2016, 10.1186/s12866-016-0625-7.
127. Kim, Y., Keogh, J.B., Clifton, P.M., Polyphenols and glycemic control. Nutrients, 8(January (1)), 2016, 10.3390/nu8010017 (pii: E17 Review).
128. Kirkland, J.L., Tchkonia, T., Cellular senescence: a translational perspective. EBioMedicine 21:July (2017), 21–28, 10.1016/j.ebiom.2017.04.013 Epub 2017 Apr 12.
129. Kitada, K., Nakano, D., Ohsaki, H., Hitomi, H., Minamino, T., Yatabe, J., Felder, R.A., Mori, H., Masaki, T., Kobori, H., Nishiyama, A., Hyperglycaemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J. Diabetes Complications 28:September–October (5) (2014), 604–611, 10.1016/j.jdiacomp.2014.05.010.
130. Knowler, W.C., Barrett-Connor, E., Fowler, S.E., Hamman, R.F., Lachin, J.M., Walker, E.A., Nathan, D.M., Diabetes Prevention Program Research Group, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346:February (6) (2002), 393–403.
131. Kobayashi, E.H., Suzuki, T., Funayama, R., Nagashima, T., Hayashi, M., Sekine, H., Tanaka, N., Moriguchi, T., Motohashi, H., Nakayama, K., Yamamoto, M., Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat. Commun., 7(May), 2016, 11624, 10.1038/ncomms11624.
132. Krishnamurthy, J., Ramsey, M.R., Ligon, K.L., Torrice, C., Koh, A., Bonner-Weir, S., Sharpless, N.E., p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:September (7110) (2006), 453–457 (Epub 2006 Sep 6).
133. Kubben, N., Zhang, W., Wang, L., Voss, T.C., Yang, J., Qu, J., Liu, G.H., Misteli, T., Repression of the antioxidant NRF2 pathway in premature ageing. Cell 165:June (6) (2016), 1361–1374, 10.1016/j.cell.2016.05.017.
134. López-Otín, C., Galluzzi, L., Freije, J.M., Madeo, F., Kroemer, G., Metabolic control of longevity. Cell 166:August (4) (2016), 802–821, 10.1016/j.cell.2016.07.031 (Review).
135. Laberge, R.M., Sun, Y., Orjalo, A.V., Patil, C.K., Freund, A., Zhou, L., Curran, S.C., Davalos, A.R., Wilson-Edell, K.A., Liu, S., Limbad, C., Demaria, M., Li, P., Hubbard, G.B., Ikeno, Y., Javors, M., Desprez, P.Y., Benz, C.C., Kapahi, P., Nelson, P.S., Campisi, J., MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat. Cell Biol. 17:August (8) (2015), 1049–1061, 10.1038/ncb3195.
136. Lecube, A., Pachón, G., Petriz, J., Hernández, C., Simó, R., Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement. PLoS One, 6(8), 2011, e23366, 10.1371/journal.pone.0023366 (Epub 2011 Aug 18).
137. Lee, J.Y., Sohn, K.H., Rhee, S.H., Hwang, D., Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J. Biol. Chem. 276:May (20) (2001), 16683–16689.
138. Levine, M.E., Suarez, J.A., Brandhorst, S., Balasubramanian, P., Cheng, C.W., Madia, F., Fontana, L., Mirisola, M.G., Guevara-Aguirre, J., Wan, J., Passarino, G., Kennedy, B.K., Wei, M., Cohen, P., Crimmins, E.M., Longo, V.D., Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 19:March (3) (2014), 407–417, 10.1016/j.cmet.2014.02.006.
139. Ley, R.E., Bäckhed, F., Turnbaugh, P., Lozupone, C.A., Knight, R.D., Gordon, J.I., Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. U. S. A. 102:August (31) (2005), 11070–11075.
140. Liu, J., Ibi, D., Taniguchi, K., Lee, J., Herrema, H., Akosman, B., Mucka, P., Salazar Hernandez, M.A., Uyar, M.F., Park, S.W., Karin, M., Ozcan, U., Inflammation improves glucose homeostasis through IKKβ-XBP1s interaction. Cell 167:November (4) (2016), 1052–1066, 10.1016/j.cell.2016.10.015 (e18).
141. Luconi, M., Cantini, G., Ceriello, A., Mannucci, E., Perspectives on cardiovascular effects of incretin-based drugs: from bedside to bench, return trip. Int. J. Cardiol. 241:August (2017), 302–310, 10.1016/j.ijcard.2017.02.126 Epub 2017 Mar 2.
142. Lumeng, C.N., Saltiel, A.R., Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121:June (6) (2011), 2111–2117, 10.1172/JCI57132 (Epub 2011 Jun 1. Review).
143. Maiese, K., New insights for oxidative stress and diabetes mellitus. Oxid. Med. Cell. Longev., 2015, 2015 (17 pages).
144. Maiese, K., Harnessing the power of SIRT1 and non-coding RNAs in vascular disease. Curr. Neurovasc. Res. 14:1 (2017), 82–88, 10.2174/1567202613666161129112822.
145. Maiorino, M.I., Bellastella, G., Petrizzo, M., Scappaticcio, L., Giugliano, D., Esposito, K., Anti-inflammatory effect of mediterranean diet in type 2 diabetes is durable: 8-year follow-up of a controlled trial. Diabetes Care 39:March (3) (2016), e44–e45, 10.2337/dc15-2356.
146. Marhoffer, W., Stein, M., Maeser, E., Federlin, K., Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care 15 (1992), 256–260.
147. Martin-Montalvo, A., Mercken, E.M., Mitchell, S.J., Palacios, H.H., Mote, P.L., Scheibye-Knudsen, M., Gomes, A.P., Ward, T.M., Minor, R.K., Blouin, M.J., Schwab, M., Pollak, M., Zhang, Y., Yu, Y., Becker, K.G., Bohr, V.A., Ingram, D.K., Sinclair, D.A., Wolf, N.S., Spindler, S.R., Bernier, M., de Cabo, R., Metformin improves healthspan and lifespan in mice. Nat. Commun., 4, 2013, 2192, 10.1038/ncomms3192.
148. Martucci, M., Ostan, R., Biondi, F., Bellavista, E., Fabbri, C., Bertarelli, C., Salvioli, S., Capri, M., Franceschi, C., Santoro, A., Mediterranean diet and inflammageing within the hormesis paradigm. Nutr. Rev., 2017, 10.1093/nutrit/nux013 (Jun 8. [Epub ahead of print]).
149. Masters, S.L., Latz, E., O'Neill, L.A., The inflammasome in atherosclerosis and type 2 diabetes. Sci. Transl. Med., 3(May (81)), 2011, 10.1126/scitranslmed.3001902 (81ps17).
150. Matsumoto, M., Kurihara, S., Kibe, R., Ashida, H., Benno, Y., Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production. PLoS One, 6(8), 2011, e23652, 10.1371/journal.pone.0023652.
151. Mattson, M.P., Wan, R., Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J. Nutr. Biochem. 16:March (3) (2005), 129–137 (Review).
152. Mattson, M.P., Longo, V.D., Harvie, M., Impact of intermittent fasting on health and disease processes. Ageing Res. Rev. 39:October (2017), 46–58, 10.1016/j.arr.2016.10.005 Epub 2016 Oct 31. Review.
153. Mazidi, M., Rezaie, P., Ferns, G.A., Vatanparast, H., Impact of probiotic administration on serum C-reactive protein concentrations: systematic review and meta-analysis of randomized control trials. Nutrients, 9(January (1)), 2017, 10.3390/nu9010020 (pii: E20. Review).
154. Mercken, E.M., Mitchell, S.J., Martin-Montalvo, A., Minor, R.K., Almeida, M., Gomes, A.P., Scheibye-Knudsen, M., Palacios, H.H., Licata, J.J., Zhang, Y., Becker, K.G., Khraiwesh, H., González-Reyes, J.A., Villalba, J.M., Baur, J.A., Elliott, P., Westphal, C., Vlasuk, G.P., Ellis, J.L., Sinclair, D.A., Bernier, M., de Cabo, R., SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Ageing Cell 13:October (5) (2014), 787–796, 10.1111/acel.12220.
155. Metchnikoff, E., The Prolongation of Life: Optimistic Studies. 1907, G.P. Putnam's Sons.
156. Michalek, R.D., Gerriets, V.A., Jacobs, S.R., Macintyre, A.N., MacIver, N.J., Mason, E.F., Sullivan, S.A., Nichols, A.G., Rathmell, J.C., Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J. Immunol. 186:March (6) (2011), 3299–3303, 10.4049/jimmunol.1003613.
157. Minamino, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., Ito, T., Nojima, A., Nabetani, A., Oike, Y., Matsubara, H., Ishikawa, F., Komuro, I., A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat. Med. 15:September (9) (2009), 1082–1087, 10.1038/nm.2014 (Epub 2009 Aug 30).
158. Moi, P., Chan, K., Asunis, I., Cao, A., Kan, Y.W., Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc. Natl. Acad. Sci. U. S. A. 91:October (21) (1994), 9926–9930, 10.1073/pnas.91.21.9926.
159. Moon, J.S., Hisata, S., Park, M.A., DeNicola, G.M., Ryter, S.W., Nakahira, K., Choi, A.M., MTORC1-induced HK1-dependent glycolysis regulates NLRP3 inflammasome activation. Cell Rep. 12:July (1) (2015), 102–115, 10.1016/j.celrep.2015.05.046 (Epub 2015 Jun 25).
160. Moreno-Asso, A., Castaño, C., Grilli, A., Novials, A., Servitja, J.M., Glucose regulation of a cell cycle gene module is selectively lost in mouse pancreatic islets during ageing. Diabetologia 56:August (8) (2013), 1761–1772, 10.1007/s00125-013-2930-0 (Epub 2013 May 18).
161. Murakami, Y., Mizoguchi, F., Saito, T., Miyasaka, N., Kohsaka, H., p16(INK4a) exerts an anti-inflammatory effect through accelerated IRAK1 degradation in macrophages. J. Immunol. 189:November (10) (2012), 5066–5072, 10.4049/jimmunol.1103156 (Epub 2012 Oct 12).
162. Nagareddy, P.R., Murphy, A.J., Stirzaker, R.A., Hu, Y., Yu, S., Miller, R.G., Ramkhelawon, B., Distel, E., Westerterp, M., Huang, L.S., Schmidt, A.M., Orchard, T.J., Fisher, E.A., Tall, A.R., Goldberg, I.J., Hyperglycaemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. 17:May (5) (2013), 695–708, 10.1016/j.cmet.2013.04.001.
163. Nathan, D.M., Cleary, P.A., Backlund, J.Y., Genuth, S.M., Lachin, J.M., Orchard, T.J., Raskin, P., Zinman, B., Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 353 (2005), 2643–2653.
164. Nilsson, E., Jansson, P.A., Perfilyev, A., Volkov, P., Pedersen, M., Svensson, M.K., Poulsen, P., Ribel-Madsen, R., Pedersen, N.L., Almgren, P., Fadista, J., Rönn, T., Klarlund Pedersen, B., Scheele, C., Vaag, A., Ling, C., Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes 63:September (9) (2014), 2962–2976, 10.2337/db13-1459 (Epub 2014 May 8).
165. Noren Hooten, N., Martin-Montalvo, A., Dluzen, D.F., Zhang, Y., Bernier, M., Zonderman, A.B., Becker, K.G., Gorospe, M., de Cabo, R., Evans, M.K., Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence. Ageing Cell 15:June (3) (2016), 572–581, 10.1111/acel.12469.
166. O'Neill, L.A., Kishton, R.J., Rathmell, J., A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 16:September (9) (2016), 553–565, 10.1038/nri.2016.70 (Epub 2016 Jul 11. Review).
167. Oelze, M., Kröller-Schön, S., Welschof, P., Jansen, T., Hausding, M., Mikhed, Y., Stamm, P., Mader, M., Zinßius, E., Agdauletova, S., Gottschlich, A., Steven, S., Schulz, E., Bottari, S.P., Mayoux, E., Münzel, T., Daiber, A., The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One, 9(November (11)), 2014, e112394, 10.1371/journal.pone.0112394 (eCollection 2014).
168. Oeseburg, H., de Boer, R.A., Buikema, H., van der Harst, P., van Gilst, W.H., Silljé, H.H., Glucagon-like peptide 1 prevents reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A. Arterioscler. Thromb. Vasc. Biol. 30:July (7) (2010), 1407–1414, 10.1161/ATVBAHA.110.206425.
169. Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C.L., Lahat, A., Day, C.P., Burt, A., Palmer, A., Anstee, Q.M., Grellscheid, S.N., Hoeijmakers, J.H.J., Barnhoorn, S., Mann, D.A., Bird, T.G., Vermeij, W.P., Kirkland, J.L., Passos, J.F., von Zglinicki, T., Jurk, D., Cellular senescence drives age-dependent hepatic steatosis. Nat. Commun., 8(June), 2017, 15691, 10.1038/ncomms15691.
170. Olivieri, F., Rippo, M.R., Prattichizzo, F., Babini, L., Graciotti, L., Recchioni, R., Procopio, A.D., Toll like receptor signaling in inflammageing: microRNA as new players. Immun. Ageing, 10(March (1)), 2013, 11, 10.1186/1742-4933-10-11.
171. Olivieri, F., Capri, M., Bonafè, M., Morsiani, C., Jung, H.J., Spazzafumo, L., Viña, J., Suh, Y., Circulating miRNAs and miRNA shuttles as biomarkers: perspective trajectories of healthy and unhealthy ageing. Mech. Ageing Dev., 2016, 10.1016/j.mad.2016.12.004 Dec 13. pii: S0047-6374(16)30185-3.[Epub ahead of print] Review.
172. Olmos, Y., Sánchez-Gómez, F.J., Wild, B., García-Quintans, N., Cabezudo, S., Lamas, S., Monsalve, M., SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex. Antioxid. Redox Signal. 19:November (13) (2013), 1507–1521, 10.1089/ars.2012.4713.
173. Párrizas, M., Novials, A., Circulating microRNAs as biomarkers for metabolic disease. Best Pract. Res. Clin. Endocrinol. Metab. 30:October (5) (2016), 591–601, 10.1016/j.beem.2016.08.001 (Epub 2016 Aug 4. Review).
174. Pérez-Martínez, P., Mikhailidis, D.P., Athyros, V.G., Bullo, M., Couture, P., Covas, M.I., de Koning, L., Delgado-Lista, J., Díaz-López, A., Drevon, C.A., Estruch, R., Esposito, K., Fitó, M., Garaulet, M., Giugliano, D., García-Ríos, A., Katsiki, N., Kolovou, G., Lamarche, B., Maiorino, M.I., Mena-Sánchez, G., Muñoz-Garach, A., Nikolic, D., Ordovás, J.M., Pérez-Jiménez, F., Rizzo, M., Salas-Salvadó, J., Schröder, H., Tinahones, F.J., de la Torre, R., van Ommen, B., Wopereis, S., Ros, E., López-Miranda, J., Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation. Nutr. Rev. 75:May (5) (2017), 307–326, 10.1093/nutrit/nux014.
175. Palmer, A.K., Tchkonia, T., LeBrasseur, N.K., Chini, E.N., Xu, M., Kirkland, J.L., Cellular senescence in type 2 diabetes: a therapeutic opportunity. Diabetes 64:July (7) (2015), 2289–2298, 10.2337/db14-1820 (Review).
176. Paneni, F., Mocharla, P., Akhmedov, A., Costantino, S., Osto, E., Volpe, M., Lüscher, T.F., Cosentino, F., Gene silencing of the mitochondrial adaptor p66(Shc) suppresses vascular hyperglycemic memory in diabetes. Circ. Res. 111:July (3) (2012), 278–289, 10.1161/CIRCRESAHA.112.266593.
177. Paneni, F., Costantino, S., Cosentino, F., Molecular mechanisms of vascular dysfunction and cardiovascular biomarkers in type 2 diabetes. Cardiovasc. Diagn. Ther. 4:August (4) (2014), 324–332, 10.3978/j.issn.2223-3652.2014.08.02 (Review).
178. Pang, B., Zhao, L.H., Zhou, Q., Zhao, T.Y., Wang, H., Gu, C.J., Tong, X.L., Application of berberine on treating type 2 diabetes mellitus. Int. J. Endocrinol., 2015, 2015, 905749, 10.1155/2015/905749 (Review).
179. Pascoe, J., Hollern, D., Stamateris, R., Abbasi, M., Romano, L.C., Zou, B., O'Donnell, C.P., Garcia-Ocana, A., Alonso, L.C., Free fatty acids block glucose-induced β-cell proliferation in mice by inducing cell cycle inhibitors p16 and p18. Diabetes 61:March (3) (2012), 632–641, 10.2337/db11-0991.
180. Pazienza, V., Borghesan, M., Mazza, T., Sheedfar, F., Panebianco, C., Williams, R., Mazzoccoli, G., Andriulli, A., Nakanishi, T., Vinciguerra, M., SIRT1-metabolite binding histone macroH2A1.1 protects hepatocytes against lipid accumulation. Ageing (Albany N. Y.) 6:January (1) (2014), 35–47.
181. Petersen, K.E., Rakipovski, G., Raun, K., Lykkesfeldt, J., Does glucagon-like peptide-1 ameliorate oxidative stress in diabetes? Evidence based on experimental and clinical studies. Curr. Diabetes Rev. 12:4 (2016), 331–358 (Review.).
182. Pickup, J.C., Mattock, M.B., Chusney, G.D., Burt, D., NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 40:November (11) (1997), 1286–1292.
183. Pirola, L., Balcerczyk, A., Okabe, J., El-Osta, A., Epigenetic phenomena linked to diabetic complications. Nat. Rev. Endocrinol. 6 (2010), 665–675.
184. Plovier, H., Everard, A., Druart, C., Depommier, C., Van Hul, M., Geurts, L., Chilloux, J., Ottman, N., Duparc, T., Lichtenstein, L., Myridakis, A., Delzenne, N.M., Klievink, J., Bhattacharjee, A., van der Ark, K.C., Aalvink, S., Martinez, L.O., Dumas, M.E., Maiter, D., Loumaye, A., Hermans, M.P., Thissen, J.P., Belzer, C., de Vos, W.M., Cani, P.D., A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med. 23:January (1) (2017), 107–113, 10.1038/nm.4236.
185. Pollack, R.M., Donath, M.Y., LeRoith, D., Leibowitz, G., Anti-inflammatory agents in the treatment of diabetes and its vascular complications. Diabetes Care 39:August (Suppl. 2) (2016), S244–S252, 10.2337/dcS15-3015.
186. Prattichizzo, F., Giuliani, A., Ceka, A., Rippo, M.R., Bonfigli, A.R., Testa, R., Procopio, A.D., Olivieri, F., Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes. Clin. Epigenet., 23(May (7)), 2015, 56, 10.1186/s13148-015-0090-4.
187. Prattichizzo, F., De Nigris, V., La Sala, L., Procopio, A.D., Olivieri, F., Ceriello, A., Inflammageing as a druggable target: a senescence-associated secretory phenotype-centered view of type 2 diabetes. Oxid. Med. Cell. Longev., 2016, 2016, 1810327, 10.1155/2016/1810327 (Review).
188. Prattichizzo, F., Giuliani, A., De Nigris, V., Pujadas, G., Ceka, A., La Sala, L., Genovese, S., Testa, R., Procopio, A.D., Olivieri, F., Ceriello, A., Extracellular microRNAs and endothelial hyperglycaemic memory: a therapeutic opportunity?. Diabet. Obes. Metab. 18:September (9) (2016), 855–867, 10.1111/dom.12688 (Epub 2016 Jun 22. Review).
189. Prattichizzo, F., Giuliani, A., Recchioni, R., Bonafè, M., Marcheselli, F., De Carolis, S., Campanati, A., Giuliodori, K., Rippo, M.R., Brugè, F., Tiano, L., Micucci, C., Ceriello, A., Offidani, A., Procopio, A.D., Olivieri, F., Anti-TNF-α treatment modulates SASP and SASP-related microRNAs in endothelial cells and in circulating angiogenic cells. Oncotarget 7:March (11) (2016), 11945–11958, 10.18632/oncotarget.7858.
190. Pujadas, G., Drucker, D.J., Vascular biology of glucagon receptor superfamily peptides: mechanistic and clinical relevance. Endocr. Rev. 37:December (6) (2016), 554–583.
191. Pujadas, G., De Nigris, V., Prattichizzo, F., La Sala, L., Testa, R., Ceriello, A., The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin functions as antioxidant on human endothelial cells exposed to chronic hyperglycaemia and metabolic high-glucose memory. Endocrine 56:June (3) (2017), 509–520, 10.1007/s12020-016-1052-0.
192. Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., Peng, Y., Zhang, D., Jie, Z., Wu, W., Qin, Y., Xue, W., Li, J., Han, L., Lu, D., Wu, P., Dai, Y., Sun, X., Li, Z., Tang, A., Zhong, S., Li, X., Chen, W., Xu, R., Wang, M., Feng, Q., Gong, M., Yu, J., Zhang, Y., Zhang, M., Hansen, T., Sanchez, G., Raes, J., Falony, G., Okuda, S., Almeida, M., LeChatelier, E., Renault, P., Pons, N., Batto, J.M., Zhang, Z., Chen, H., Yang, R., Zheng, W., Li, S., Yang, H., Wang, J., Ehrlich, S.D., Nielsen, R., Pedersen, O., Kristiansen, K., Wang, J., A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:October (7418) (2012), 55–60, 10.1038/nature11450.
193. Quach, A., Levine, M.E., Tanaka, T., Lu, A.T., Chen, B.H., Ferrucci, L., Ritz, B., Bandinelli, S., Neuhouser, M.L., Beasley, J.M., Snetselaar, L., Wallace, R.B., Tsao, P.S., Absher, D., Assimes, T.L., Stewart, J.D., Li, Y., Hou, L., Baccarelli, A.A., Whitsel, E.A., Horvath, S., Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging (Albany N. Y.) 9:February (2) (2017), 419–446, 10.18632/aging.101168.
194. Rönn, T., Ling, C., DNA methylation as a diagnostic and therapeutic target in the battle against type 2 diabetes. Epigenomics 7:3 (2015), 451–460, 10.2217/epi.15.7 (Review).
195. Rajapakse, A.G., Yepuri, G., Carvas, J.M., Stein, S., Matter, C.M., Scerri, I., Ruffieux, J., Montani, J.P., Ming, X.F., Yang, Z., Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in ageing: inhibition by resveratrol. PLoS One, 6(April (4)), 2011, e19237, 10.1371/journal.pone.0019237.
196. Ranieri, S.C., Fusco, S., Panieri, E., Labate, V., Mele, M., Tesori, V., Ferrara, A.M., Maulucci, G., De Spirito, M., Martorana, G.E., Galeotti, T., Pani, G., Mammalian life-span determinant p66shcA mediates obesity-induced insulin resistance. Proc. Natl. Acad. Sci. U. S. A. 107:July (30) (2010), 13420–13425, 10.1073/pnas.1008647107.
197. Rawshani, A., Rawshani, A., Franzén, S., Eliasson, B., Svensson, A.M., Miftaraj, M., McGuire, D.K., Sattar, N., Rosengren, A., Gudbjörnsdottir, S., Mortality and cardiovascular disease in type 1 and type 2 diabetes. N. Engl. J. Med. 376:April (15) (2017), 1407–1418, 10.1056/NEJMoa1608664.
198. Reddy, M.A., Zhang, E., Natarajan, R., Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia 58 (2015), 443–455.
199. Ribel-Madsen, R., Fraga, M.F., Jacobsen, S., et al. Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for Type 2 diabetes. PLoS One, 7(12), 2012, e51302.
200. Roberts, M.N., Wallace, M.A., Tomilov, A.A., Zhou, Z., Marcotte, G.R., Tran, D., Perez, G., Gutierrez-Casado, E., Koike, S., Knotts, T.A., Imai, D.M., Griffey, S.M., Kim, K., Hagopian, K., Haj, F.G., Baar, K., Cortopassi, G.A., Ramsey, J.J., Lopez-Dominguez, J.A., A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab. 26:September (3) (2017), 539–546, 10.1016/j.cmet.2017.08.005 (e5).
201. Round, J.L., Mazmanian, S.K., The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9:5 (2009), 313–323.
202. Sahoo, S., Emanueli, C., Exosomes in diabetic cardiomyopathy: the next-generation therapeutic targets?. Diabetes 65:October (10) (2016), 2829–2831, 10.2337/dbi16-0041.
203. Salminen, A., Kauppinen, A., Kaarniranta, K., Emerging role of NF-(B signaling in the induction of senescence-associated secretory phenotype (SASP). Cell. Signal. 24:April (4) (2012), 835–845, 10.1016/j.cellsig.2011.12.006 (Epub 2011 Dec 11. Review.).
204. Sanders, Y.Y., Liu, H., Zhang, X., Hecker, L., Bernard, K., Desai, L., Liu, G., Thannickal, V.J., Histone modifications in senescence-associated resistance to apoptosis by oxidative stress. Redox Biol. 1:January (2013), 8–16, 10.1016/j.redox.2012.11.004.
205. Sandovici, I., Hammerle, C.M., Cooper, W.N., Smith, N.H., Tarry-Adkins, J.L., Dunmore, B.J., Bauer, J., Andrews, S.R., Yeo, G.S., Ozanne, S.E., Constância, M., Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets. Diabetologia 59:March (3) (2016), 502–511, 10.1007/s00125-015-3837-8.
206. Schafer, M.J., White, T.A., Evans, G., Tonne, J.M., Verzosa, G.C., Stout, M.B., Mazula, D.L., Palmer, A.K., Baker, D.J., Jensen, M.D., Torbenson, M.S., Miller, J.D., Ikeda, Y., Tchkonia, T., van Deursen, J.M., Kirkland, J.L., LeBrasseur, N.K., Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes 65:June (6) (2016), 1606–1615, 10.2337/db15-0291 (Epub 2016 Mar 16).
207. Schisano, B., Tripathi, G., McGee, K., McTernan, P.G., Ceriello, A., Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells. Diabetologia 54:May (5) (2011), 1219–1226, 10.1007/s00125-011-2049-0.
208. Schnell, O., Standl, E., Catrinoiu, D., Genovese, S., Lalic, N., Skra, J., Valensi, P., Rahelic, D., Ceriello, A., Report from the 2nd cardiovascular outcome trial (CVOT) summit of the diabetes and cardiovascular disease (D&CVD) EASD study group. Cardiovasc. Diabetol., 16(March (1)), 2017, 35, 10.1186/s12933-017-0508-8.
209. Schulz, T.J., Zarse, K., Voigt, A., Urban, N., Birringer, M., Ristow, M., Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 6:October (4) (2007), 280–293.
210. Shahzad, K., Bock, F., Al-Dabet, M.M., Gadi, I., Nazir, S., Wang, H., Kohli, S., Ranjan, S., Mertens, P.R., Nawroth, P.P., Isermann, B., Stabilization of endogenous Nrf2 by minocycline protects against Nlrp3-inflammasome induced diabetic nephropathy. Sci. Rep., 6(October), 2016, 34228, 10.1038/srep34228.
211. Shi, L.Z., Wang, R., Huang, G., Vogel, P., Neale, G., Green, D.R., Chi, H., HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 208:July (7) (2011), 1367–1376, 10.1084/jem.20110278.
212. Shinohara, T., Takahashi, N., Okada, N., Ayabe, R., Kondo, H., et al. Interleukin-6 as an independent predictor of future cardiovascular events in patients with type-2 diabetes without structural heart disease. J. Clin. Exp. Cardiol., 3, 2012, 209, 10.4172/2155-9880.1000209.
213. Shu, C.J., Benoist, C., Mathis, D., The immune system's involvement in obesity-driven type 2 diabetes. Semin. Immunol. 24:December (6) (2012), 436–442, 10.1016/j.smim.2012.12.001 (Epub 2013 Jan 18. Review.).
214. Simpson, S.J., Le Couteur, D.G., Raubenheimer, D., Solon-Biet, S.M., Cooney, G.J., Cogger, V.C., Fontana, L., Dietary protein, ageing and nutritional geometry. Ageing Res. Rev. 39:October (2017), 78–86, 10.1016/j.arr.2017.03.001 Epub 2017 Mar 6. Review.
215. Siri-Tarino, P.W., Sun, Q., Hu, F.B., Krauss, R.M., Saturated fat, carbohydrate, and cardiovascular disease. Am. J. Clin. Nutr. 91:March (3) (2010), 502–509, 10.3945/ajcn.2008.26285 (Review).
216. Song, R., Mechanism of metformin: a tale of two sites. Diabetes Care 39:February (2) (2016), 187–189, 10.2337/dci15-0013.
217. Sousa-Victor, P., Gutarra, S., García-Prat, L., Rodriguez-Ubreva, J., Ortet, L., Ruiz-Bonilla, V., Jardí, M., Ballestar, E., González, S., Serrano, A.L., Perdiguero, E., Muñoz-Cánoves, P., Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506:February (7488) (2014), 316–321, 10.1038/nature13013 (Epub 2014 Feb 12).
218. Spiga, R., Marini, M.A., Mancuso, E., Di Fatta, C., Fuoco, A., Perticone, F., Andreozzi, F., Mannino, G.C., Sesti, G., Uric acid is associated with inflammatory biomarkers and induces inflammation via activating the NF-κB signaling pathway in HepG2 cells. Arterioscler. Thromb. Vasc. Biol. 37:June (6) (2017), 1241–1249, 10.1161/ATVBAHA.117.309128.
219. Standl, E., Schnell, O., McGuire, D.K., Ceriello, A., Rydén, L., Integration of recent evidence into management of patients with atherosclerotic cardiovascular disease and type 2 diabetes. Lancet Diabetes Endocrinol. 5:May (5) (2017), 391–402, 10.1016/S2213-8587(17)30033-5.
220. Steer, K.A., Sochor, M., McLean, P., Renal hypertrophy in experimental diabetes. Changes in pentose phosphate pathway activity. Diabetes 34:May (5) (1985), 485–490.
221. Strong, R., Miller, R.A., Antebi, A., Astle, C.M., Bogue, M., Denzel, M.S., Fernandez, E., Flurkey, K., Hamilton, K.L., Lamming, D.W., Javors, M.A., de Magalhães, J.P., Martinez, P.A., McCord, J.M., Miller, B.F., Müller, M., Nelson, J.F., Ndukum, J., Rainger, G.E., Richardson, A., Sabatini, D.M., Salmon, A.B., Simpkins, J.W., Steegenga, W.T., Nadon, N.L., Harrison, D.E., Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Ageing Cell 15:October (5) (2016), 872–884, 10.1111/acel.12496.
222. Szarc vel Szic, K., Declerck, K., Vidaković, M., Vanden Berghe, W., From inflammageing to healthy ageing by dietary lifestyle choices: is epigenetics the key to personalized nutrition?. Clin. Epigenet., 7(March), 2015, 33, 10.1186/s13148-015-0068-2 (eCollection 2015).
223. Szkudelski, T., Szkudelska, K., Resveratrol and diabetes: from animal to human studies. Biochim. Biophys. Acta 1852:June (6) (2015), 1145–1154, 10.1016/j.bbadis.2014.10.013 (Review).
224. Tanaka, M., Masuda, S., Matsuo, Y., Sasaki, Y., Yamakage, H., Muranaka, K., Wada, H., Hasegawa, K., Tsukahara, T., Shimatsu, A., Satoh-Asahara, N., Hyperglycaemia and inflammatory property of circulating monocytes are associated with inflammatory property of carotid plaques in patients undergoing carotid endarterectomy. J. Atheroscler. Thromb. 23:October (10) (2016), 1212–1221.
225. Tannahill, G.M., Curtis, A.M., Adamik, J., Palsson-McDermott, E.M., McGettrick, A.F., Goel, G., Frezza, C., Bernard, N.J., Kelly, B., Foley, N.H., Zheng, L., Gardet, A., Tong, Z., Jany, S.S., Corr, S.C., Haneklaus, M., Caffrey, B.E., Pierce, K., Walmsley, S., Beasley, F.C., Cummins, E., Nizet, V., Whyte, M., Taylor, C.T., Lin, H., Masters, S.L., Gottlieb, E., Kelly, V.P., Clish, C., Auron, P.E., Xavier, R.J., O'Neill, L.A., Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496:April (7444) (2013), 238–242, 10.1038/nature11986.
226. Tao, S.C., Guo, S.C., Li, M., Ke, Q.F., Guo, Y.P., Zhang, C.Q., Chitosan wound dressings incorporating exosomes derived from microRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model. Stem Cells Transl. Med. 6:March (3) (2017), 736–747, 10.5966/sctm.2016-0275.
227. Tchkonia, T., Morbeck, D.E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M.D., Kirkland, J.L., Fat tissue, ageing, and cellular senescence. Ageing Cell 9 (2010), 667–684.
228. Thaler, J.P., Yi, C.X., Schur, E.A., Guyenet, S.J., Hwang, B.H., Dietrich, M.O., Zhao, X., Sarruf, D.A., Izgur, V., Maravilla, K.R., Nguyen, H.T., Fischer, J.D., Matsen, M.E., Wisse, B.E., Morton, G.J., Horvath, T.L., Baskin, D.G., Tschöp, M.H., Schwartz, M.W., Obesity is associated with hypothalamic injury in rodents and humans. J. Clin. Invest. 122:January (1) (2012), 153–162, 10.1172/JCI59660 (Epub 2011 Dec 27).
229. Thevaranjan, N., Puchta, A., Schulz, C., Naidoo, A., Szamosi, J.C., Verschoor, C.P., Loukov, D., Schenck, L.P., Jury, J., Foley, K.P., Schertzer, J.D., Larché, M.J., Davidson, D.J., Verdú, E.F., Surette, M.G., Bowdish, D.M., Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe 21:April (4) (2017), 455–466, 10.1016/j.chom.2017.03.002 (e4).
230. Timmers, S., de Ligt, M., Phielix, E., van de Weijer, T., Hansen, J., Moonen-Kornips, E., Schaart, G., Kunz, I., Hesselink, M.K., Schrauwen-Hinderling, V.B., Schrauwen, P., Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: a randomized controlled trial. Diabetes Care 39:December (12) (2016), 2211–2217.
231. Tzeng, Y.L., Datta, A., Kolli, V.K., Carlson, R.W., Stephens, D.S., Endotoxin of Neisseria meningitidis composed only of intact lipid A: inactivation of the meningococcal 3-deoxy-D-manno-octulosonic acid transferase. J. Bacteriol. 184:May (9) (2002), 2379–2388.
232. UKPDS, UK Prospective Diabetes Study Group, Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. BMJ 317:September (7160) (1998), 703–713.
233. van Greevenbroek, M.M., Schalkwijk, C.G., Stehouwer, C.D., Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and consequences. Neth. J. Med. 71:May (4) (2013), 174–187 (Review).
234. Vaiserman, A.M., Koliada, A.K., Marotta, F., Gut microbiota: a player in ageing and a target for anti-ageing intervention. Ageing Res. Rev. 35:May (2017), 36–45, 10.1016/j.arr.2017.01.001 (Review).
235. Vander Heiden, M.G., Cantley, L.C., Thompson, C.B., Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:May (5930) (2009), 1029–1033, 10.1126/science.1160809 (Review).
236. Velarde, M.C., Flynn, J.M., Day, N.U., Melov, S., Campisi, J., Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and ageing phenotypes in the skin. Ageing (Albany N. Y.) 4:January (1) (2012), 3–12.
237. Vikram, A., Kim, Y.R., Kumar, S., Li, Q., Kassan, M., Jacobs, J.S., Irani, K., Vascular microRNA-204 is remotely governed by the microbiome and impairs endothelium-dependent vasorelaxation by downregulating Sirtuin1. Nat. Commun., 7(September), 2016 Sep, 12565, 10.1038/ncomms12565.
238. Villaret, A., Galitzky, J., Decaunes, P., Estève, D., Marques, M.A., Sengenès, C., Chiotasso, P., Tchkonia, T., Lafontan, M., Kirkland, J.L., Bouloumié, A., Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. Diabetes 59:November (11) (2010), 2755–2763, 10.2337/db10-0398 (Epub 2010 Aug 16).
239. Wärnberg, J., Cunningham, K., Romeo, J., Marcos, A., Physical activity, exercise and low-grade systemic inflammation. Proc. Nutr. Soc. 69:August (3) (2010), 400–406, 10.1017/S0029665110001928 (Epub 2010 Jul 2. Review).
240. Wagner, W., Epigenetic ageing clocks in mice and men. Genome Biol., 18(June (1)), 2017, 107, 10.1186/s13059-017-1245-8.
241. Wang, X., Bao, W., Liu, J., Ouyang, Y.Y., Wang, D., Rong, S., Xiao, X., Shan, Z.L., Zhang, Y., Yao, P., Liu, L.G., Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 36:January (1) (2013), 166–175, 10.2337/dc12-0702 (Review).
242. Wang, X., He, G., Peng, Y., Zhong, W., Wang, Y., Zhang, B., Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway. Sci. Rep., 5(August), 2015, 12676, 10.1038/srep12676.
243. Wei, M., Brandhorst, S., Shelehchi, M., Mirzaei, H., Cheng, C.W., Budniak, J., Groshen, S., Mack, W.J., Guen, E., Di Biase, S., Cohen, P., Morgan, T.E., Dorff, T., Hong, K., Michalsen, A., Laviano, A., Longo, V.D., Fasting-mimicking diet and markers/risk factors for ageing, diabetes, cancer, and cardiovascular disease. Sci. Transl. Med., 9(February (377)), 2017 (pii: eaai8700).
244. Weichhart, T., Hengstschläger, M., Linke, M., Regulation of innate immune cell function by mTOR. Nat. Rev. Immunol. 15:October (10) (2015), 599–614, 10.1038/nri3901 (Review).
245. Wiley, C.D., Campisi, J., From ancient pathways to ageing cells-connecting metabolism and cellular senescence. Cell Metab. 23:June (6) (2016), 1013–1021, 10.1016/j.cmet.2016.05.010 (Review).
246. Woods, J.A., Wilund, K.R., Martin, S.A., Kistler, B.M., Exercise, inflammation and aging. Aging Dis. 3:February (1) (2012), 130–140 (Epub 2011 Oct 29).
247. Wu, L., Zhou, B., Oshiro-Rapley, N., Li, M., Paulo, J.A., Webster, C.M., Mou, F., Kacergis, M.C., Talkowski, M.E., Carr, C.E., Gygi, S.P., Zheng, B., Soukas, A.A., An ancient, unified mechanism for metformin growth inhibition in C. elegans and cancer. Cell 167:December (7) (2016), 1705–1718, 10.1016/j.cell.2016.11.055 (e13).
248. Xie, M., Yu, Y., Kang, R., Zhu, S., Yang, L., Zeng, L., Sun, X., Yang, M., Billiar, T.R., Wang, H., Cao, L., Jiang, J., Tang, D., PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nat. Commun., 25(October (7)), 2016, 13280, 10.1038/ncomms13280.
249. Xu, M., Palmer, A.K., Ding, H., Weivoda, M.M., Pirtskhalava, T., White, T.A., Sepe, A., Johnson, K.O., Stout, M.B., Giorgadze, N., Jensen, M.D., LeBrasseur, N.K., Tchkonia, T., Kirkland, J.L., Targeting senescent cells enhances adipogenesis and metabolic function in old age. Elife, 4(December), 2015, e12997, 10.7554/eLife.12997.
250. Yang, Y., Wang, J., Qin, L., Shou, Z., Zhao, J., Wang, H., et al. Rapamycin prevents early steps of the development of diabetic nephropathy in rats. Am. J. Nephrol. 27 (2007), 495–502.
251. Yoshimoto, S., Loo, T.M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., Honda, K., Ishikawa, Y., Hara, E., Ohtani, N., Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499:July (7456) (2013), 97–101, 10.1038/nature12347.
252. Yoshizaki, T., Schenk, S., Imamura, T., Babendure, J.L., Sonoda, N., Bae, E.J., Oh, D.Y., Lu, M., Milne, J.C., Westphal, C., Bandyopadhyay, G., Olefsky, J.M., SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am. J. Physiol. Endocrinol. Metab. 298:March (3) (2010), E419–E428, 10.1152/ajpendo.00417.2009.
253. Youm, Y.H., Nguyen, K.Y., Grant, R.W., Goldberg, E.L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T.D., Kang, S., Horvath, T.L., Fahmy, T.M., Crawford, P.A., Biragyn, A., Alnemri, E., Dixit, V.D., The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat. Med. 21:March (3) (2015), 263–269, 10.1038/nm.3804.
254. Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., Cai, D., Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135:1 (2008), 61–73.
255. Zhang, G., Li, J., Purkayastha, S., Tang, Y., Zhang, H., Yin, Y., Li, B., Liu, G., Cai, D., Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature 497:May (7448) (2013), 211–216, 10.1038/nature12143 (Epub 2013 May 1).
256. Zhang, Y., Sun, X., Icli, B., Feinberg, M.W., Emerging roles for MicroRNAs in diabetic microvascular disease: novel targets for therapy. Endocr. Rev. 2017:April (1) (2017), 1–22, 10.1210/er.2016-1122.2017.1.test.
257. Zhao, J., Goldberg, J., Bremner, J.D., Vaccarino, V., Global DNA methylation is associated with insulin resistance: a monozygotic twin study. Diabetes 61:February (2) (2012), 542–546, 10.2337/db11-1048 (Epub 2011 Dec 30).
258. Zhao, D., Yang, J., Yang, L., Insights for oxidative stress and mTOR signaling in myocardial ischemia/reperfusion injury under diabetes. Oxid. Med. Cell. Longev., 2017, 2017, 6437467, 10.1155/2017/6437467 (Review).
259. Zhong, Q., Kowluru, R.A., Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy. Diabetes 60:April (4) (2011), 1304–1313, 10.2337/db10-0133.
260. Zhu, Y., Tchkonia, T., Fuhrmann-Stroissnigg, H., Dai, H.M., Ling, Y.Y., Stout, M.B., Pirtskhalava, T., Giorgadze, N., Johnson, K.O., Giles, C.B., Wren, J.D., Niedernhofer, L.J., Robbins, P.D., Kirkland, J.L., Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Ageing Cell 15:June (3) (2016), 428–435, 10.1111/acel.12445 (Epub 2016 Mar 18).
261. Zwerschke, W., Mazurek, S., Stöckl, P., Hütter, E., Eigenbrodt, E., Jansen-Dürr, P., Metabolic analysis of senescent human fibroblasts reveals a role for AMP in cellular senescence. Biochem. J. 376:December (Pt. 2) (2003), 403–411.