About this Journal Submit a Manuscript Table of Contents
Oxidative Medicine and Cellular Longevity
Volume 2012 (2012), Article ID 741468, 20 pages
http://dx.doi.org/10.1155/2012/741468
Review Article

Diet and Aging

Institute of Pathophysiology, Medical Faculty, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia

Received 1 June 2012; Revised 12 July 2012; Accepted 16 July 2012

Academic Editor: Paula Ludovico

Copyright © 2012 Samo Ribarič. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. A. Mckay and J. C. Mathers, “Diet induced epigenetic changes and their implications for health,” Acta Physiologica, vol. 202, no. 2, pp. 103–118, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. “Diet, nutrition and the prevention of chronic diseases,” World Health Organization Technical Report Series, vol. 916, no. 1–8, pp. 1–149, 2003.
  3. D. J. P. Barker and C. Osmond, “Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales,” The Lancet, vol. 1, no. 8489, pp. 1077–1081, 1986. View at Scopus
  4. O. A. Kensara, S. A. Wootton, D. I. Phillips, M. Patel, A. A. Jackson, and M. Elia, “Fetal programming of body composition: relation between birth weight and body composition measured with dual-energy X-ray absorptiometry and anthropometric methods in older Englishmen,” The American Journal of Clinical Nutrition, vol. 82, no. 5, pp. 980–987, 2005. View at Scopus
  5. C. Osmond, D. J. P. Barker, P. D. Winter, C. H. D. Fall, and S. J. Simmonds, “Early growth and death from cardiovascular disease in women,” British Medical Journal, vol. 307, no. 6918, pp. 1519–1524, 1993. View at Scopus
  6. C. N. Hales and D. J. P. Barker, “Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis,” Diabetologia, vol. 35, no. 7, pp. 595–601, 1992. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Cooper, C. Fall, P. Egger, R. Hobbs, R. Eastell, and D. Barker, “Growth in infancy and bone mass in later life,” Annals of the Rheumatic Diseases, vol. 56, no. 1, pp. 17–21, 1997. View at Scopus
  8. S. E. Ozanne and C. N. Hales, “Lifespan: catch-up growth and obesity in male mice,” Nature, vol. 427, no. 6973, pp. 411–412, 2004. View at Scopus
  9. V. M. Vehaskari, “Prenatal programming of kidney disease,” Current Opinion in Pediatrics, vol. 22, no. 2, pp. 176–182, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Gabory, L. Attig, and C. Junien, “Sexual dimorphism in environmental epigenetic programming,” Molecular and Cellular Endocrinology, vol. 304, no. 1-2, pp. 8–18, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. A. Bird, “DNA methylation patterns and epigenetic memory,” Genes & Development, vol. 16, no. 1, pp. 6–21, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Wu, J. Tao, and Y. E. Sun, “Regulation and function of mammalian DNA methylation patterns: a genomic perspective,” Briefings in Functional Genomics, vol. 11, no. 3, pp. 240–250, 2012.
  13. X. Zou, W. Ma, I. A. Solov'yov, C. Chipot, and K. Schulten, “Recognition of methylated DNA through methyl-CpG binding domain proteins,” Nucleic Acids Research, vol. 40, no. 6, pp. 2747–2758, 2012.
  14. K. S. Crider, T. P. Yang, R. J. Berry, and L. B. Bailey, “Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role,” Advances in Nutrition, vol. 3, no. 1, pp. 21–38, 2012.
  15. T. A. Rauch, X. Zhong, X. Wu et al., “High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 1, pp. 252–257, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Ehrlich, “DNA hypomethylation in cancer cells,” Epigenomics, vol. 1, pp. 239–259, 2009.
  17. C. D. Davis, E. O. Uthus, and J. W. Finley, “Dietary selenium and arsenic affect DNA methylation in vitro in Caco-2 cells and in vivo in rat liver and colon,” The Journal of Nutrition, vol. 130, no. 12, pp. 2903–2909, 2000. View at Scopus
  18. H. Zeng, L. Yan, W. H. Cheng, and E. O. Uthus, “Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa,” The Journal of Nutrition, vol. 141, no. 8, pp. 1464–1468, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. E. M. E. Van Straten, V. W. Bloks, N. C. A. Huijkman et al., “The liver X-receptor gene promoter is hypermethylated in a mouse model of prenatal protein restriction,” American Journal of Physiology, vol. 298, no. 2, pp. R275–R282, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. A. J. Bannister and T. Kouzarides, “Regulation of chromatin by histone modifications,” Cell Research, vol. 21, no. 3, pp. 381–395, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Link, F. Balaguer, and A. Goel, “Cancer chemoprevention by dietary polyphenols: promising role for epigenetics,” Biochemical Pharmacology, vol. 80, no. 12, pp. 1771–1792, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. X. Cheng and R. M. Blumenthal, “Coordinated chromatin control: structural and functional linkage of DNA and histone methylation,” Biochemistry, vol. 49, no. 14, pp. 2999–3008, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. Tan, B. Zhang, T. Wu et al., “Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells,” BMC Molecular Biology, vol. 10, article 12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. P. G. Hawkins and K. V. Morris, “RNA and transcriptional modulation of gene expression,” Cell Cycle, vol. 7, no. 5, pp. 602–607, 2008. View at Scopus
  25. D. P. Bartel, “MicroRNAs: target recognition and regulatory functions,” Cell, vol. 136, no. 2, pp. 215–233, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. B. Kusenda, M. Mraz, J. Mayer, and S. Pospisilova, “MicroRNA biogenesis, functionality and cancer relevance,” Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, vol. 150, no. 2, pp. 205–215, 2006. View at Scopus
  27. I. Bentwich, A. Avniel, Y. Karov et al., “Identification of hundreds of conserved and nonconserved human microRNAs,” Nature Genetics, vol. 37, no. 7, pp. 766–770, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. B. P. Lewis, C. B. Burge, and D. P. Bartel, “Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets,” Cell, vol. 120, no. 1, pp. 15–20, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. R. C. Friedman, K. K. H. Farh, C. B. Burge, and D. P. Bartel, “Most mammalian mRNAs are conserved targets of microRNAs,” Genome Research, vol. 19, no. 1, pp. 92–105, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. L. P. Lim, N. C. Lau, E. G. Weinstein et al., “The microRNAs of Caenorhabditis elegans,” Genes & Development, vol. 17, no. 8, pp. 991–1008, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Esquela-Kerscher and F. J. Slack, “Oncomirs—microRNAs with a role in cancer,” Nature Reviews Cancer, vol. 6, no. 4, pp. 259–269, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. J. C. Mathers, G. Strathdee, and C. L. Relton, “Induction of epigenetic alterations by dietary and other environmental factors,” Advances in Genetics, vol. 71, pp. 4–39, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. D. Milenkovic, C. Deval, E. Gouranton, et al., “Modulation of miRNA expression by dietary polyphenols in apoE deficient mice: a new mechanism of the action of polyphenols,” PLoS One, vol. 7, no. 1, Article ID e29837, 2012.
  34. Q. Sun, R. Cong, H. Yan et al., “Genistein inhibits growth of human uveal melanoma cells and affects microRNA-27a and target gene expression,” Oncology Reports, vol. 22, no. 3, pp. 563–567, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Sun, Z. Estrov, Y. Ji, K. R. Coombes, D. H. Harris, and R. Kurzrock, “Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells,” Molecular Cancer Therapeutics, vol. 7, no. 3, pp. 464–473, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Yang, Y. Cao, J. Sun, and Y. Zhang, “Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells,” Medical Oncology, vol. 27, no. 4, pp. 1114–1118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Careccia, S. Mainardi, A. Pelosi et al., “A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes,” Oncogene, vol. 28, no. 45, pp. 4034–4040, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. F. U. Weiss, I. J. Marques, J. M. Woltering et al., “Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer,” Gastroenterology, vol. 137, no. 6, pp. 2136–2145, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. L. A. Davidson, N. Wang, M. S. Shah, J. R. Lupton, I. Ivanov, and R. S. Chapkin, “n-3 Polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon,” Carcinogenesis, vol. 30, no. 12, pp. 2077–2084, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. T. Melkamu, X. Zhang, J. Tan, Y. Zeng, and F. Kassie, “Alteration of microRNA expression in vinyl carbamate-induced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol,” Carcinogenesis, vol. 31, no. 2, Article ID bgp208, pp. 252–258, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. C. J. Marsit, K. Eddy, and K. T. Kelsey, “MicroRNA responses to cellular stress,” Cancer Research, vol. 66, no. 22, pp. 10843–10848, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. H. Kutay, S. Bai, J. Datta et al., “Downregulation of miR-122 in the rodent and human hepatocellular carcinomas,” Journal of Cellular Biochemistry, vol. 99, no. 3, pp. 671–678, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. R. Loewith and M. N. Hall, “Target of rapamycin (TOR) in nutrient signaling and growth control,” Genetics, vol. 189, no. 4, pp. 1177–1201, 2011.
  44. M. Laplante and D. M. Sabatini, “mTOR signaling in growth control and disease,” Cell, vol. 149, no. 2, pp. 274–293, 2012.
  45. W. L. Yen and D. J. Klionsky, “How to live long and prosper: autophagy, mitochondria, and aging,” Physiology, vol. 23, no. 5, pp. 248–262, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. L. R. Pearce, D. Komander, and D. R. Alessi, “The nuts and bolts of AGC protein kinases,” Nature Reviews, vol. 11, no. 1, pp. 9–22, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. Sancak, C. C. Thoreen, T. R. Peterson et al., “PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase,” Molecular Cell, vol. 25, no. 6, pp. 903–915, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. C. A. Easley IV, A. Ben-Yehudah, C. J. Redinger et al., “MTOR-mediated activation of p70 S6K induces differentiation of pluripotent human embryonic stem cells,” Cellular Reprogramming, vol. 12, no. 3, pp. 263–273, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. L. A. Julien, A. Carriere, J. Moreau, and P. P. Roux, “mTORC1-activated S6K1 phosphorylates rictor on threonine 1135 and regulates mTORC2 signaling,” Molecular and Cellular Biology, vol. 30, no. 4, pp. 908–921, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Y. Choo, S. O. Yoon, S. G. Kim, P. P. Roux, and J. Blenis, “Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 45, pp. 17414–17419, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. D. Zhang, R. Contu, M. V. G. Latronico et al., “MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice,” The Journal of Clinical Investigation, vol. 120, no. 8, pp. 2805–2816, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. R. J. O. Dowling, I. Topisirovic, T. Alain et al., “mTORCI-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs,” Science, vol. 328, no. 5982, pp. 1172–1176, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. K. G. Foster, H. A. Acosta-Jaquez, Y. Romeo et al., “Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation,” The Journal of Biological Chemistry, vol. 285, no. 1, pp. 80–94, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. D. Kwak, S. Choi, H. Jeong, et al., “Osmotic stress regulates mammalian target of rapamycin(mTOR) complex 1 via c-Jun N-terminal Kinase (JNK)-mediated Raptor protein phosphorylation,” The Journal of Biological Chemistry, vol. 287, no. 22, pp. 18398–18407, 2012.
  55. T. Sato, A. Nakashima, L. Guo, and F. Tamanoi, “Specific activation of mTORC1 by Rheb G-protein in vitro involves enhanced recruitment of its substrate protein,” The Journal of Biological Chemistry, vol. 284, no. 19, pp. 12783–12791, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. D. M. Gwinn, D. B. Shackelford, D. F. Egan et al., “AMPK phosphorylation of raptor mediates a metabolic checkpoint,” Molecular Cell, vol. 30, no. 2, pp. 214–226, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. B. Magnuson, B. Ekim, and D. C. Fingar, “Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks,” The Biochemical Journal, vol. 441, no. 1, pp. 1–21, 2012.
  58. B. C. Melnik, “Excessive Leucine-mTORC1-signalling of cow milk-based infant formula: the missing link to understand early childhood obesity,” Journal of Obesity, vol. 2012, Article ID 197653, 2012.
  59. A. K. A. DeHart, J. D. Schnell, D. A. Allen, J. Y. Tsai, and L. Hicke, “Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway,” Molecular Biology of the Cell, vol. 14, no. 11, pp. 4676–4684, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. T. Powers, S. Aronova, and B. Niles, “TORC2 and sphingolipid biosynthesis and signaling. lessons from budding yeast,” The Enzymes, vol. 27, pp. 177–197, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. V. Zinzalla, D. Stracka, W. Oppliger, and M. N. Hall, “Activation of mTORC2 by association with the ribosome,” Cell, vol. 144, no. 5, pp. 757–768, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. A. Hagiwara, M. Cornu, N. Cybulski, et al., “Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c,” Cell Metabolism, vol. 15, no. 5, pp. 725–738, 2012.
  63. N. Cybulski and M. N. Hall, “TOR complex 2: a signaling pathway of its own,” Trends in Biochemical Sciences, vol. 34, no. 12, pp. 620–627, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. C. A. Sparks and D. A. Guertin, “Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy,” Oncogene, vol. 29, no. 26, pp. 3733–3744, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. N. Ikai, N. Nakazawa, T. Hayashi, and M. Yanagida, “The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe,” Open Biology, vol. 1, 2011. View at Publisher · View at Google Scholar
  66. M. A. Frias, C. C. Thoreen, J. D. Jaffe et al., “mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s,” Current Biology, vol. 16, no. 18, pp. 1865–1870, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. C. M. McCay, M. F. Crowell, and L. A. Maynard, “The effect of retarded growth upon the Length of life span and upon the ultimate body size,” The Journal of Nutrition, vol. 10, no. 1, pp. 63–79, 1935.
  68. R. J. Colman, R. M. Anderson, S. C. Johnson et al., “Caloric restriction delays disease onset and mortality in rhesus monkeys,” Science, vol. 325, no. 5937, pp. 201–204, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. R. Anderson and R. Weindruch, “Metabolic reprogramming in dietary restriction,” Interdisciplinary Topics in Gerontology, vol. 35, pp. 18–38, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. B. K. Kennedy, K. K. Steffen, and M. Kaeberlein, “Ruminations on dietary restriction and aging,” Cellular and Molecular Life Sciences, vol. 64, no. 11, pp. 1323–1328, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. M. D. W. Piper and A. Bartke, “Diet and aging,” Cell Metabolism, vol. 8, no. 2, pp. 99–104, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. G. S. Roth, D. K. Ingram, and M. A. Lane, “Caloric restriction in primates and relevance to humans,” Annals of the New York Academy of Sciences, vol. 928, pp. 305–315, 2001. View at Scopus
  73. R. L. Walford, D. Mock, R. Verdery, and T. MacCallum, “Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period,” The Journals of Gerontology A, vol. 57, no. 6, pp. B211–B224, 2002. View at Scopus
  74. L. Fontana, T. E. Meyer, S. Klein, and J. O. Holloszy, “Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 17, pp. 6659–6663, 2004. View at Publisher · View at Google Scholar · View at Scopus
  75. V. Tsagareli, M. Noakes, and R. J. Norman, “Effect of a very-low-calorie diet on in vitro fertilization outcomes,” Fertility and Sterility, vol. 86, no. 1, pp. 227–229, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. L. K. Heilbronn, L. De Jonge, M. I. Frisard et al., “Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial,” Journal of the American Medical Association, vol. 295, no. 13, pp. 1539–1548, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. S. B. Racette, E. P. Weiss, D. T. Villareal et al., “One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue,” The Journals of Gerontology A, vol. 61, no. 9, pp. 943–950, 2006. View at Scopus
  78. T. E. Meyer, S. J. Kovács, A. A. Ehsani, S. Klein, J. O. Holloszy, and L. Fontana, “Long-term caloric restriction ameliorates the decline in diastolic function in humans,” Journal of the American College of Cardiology, vol. 47, no. 2, pp. 398–402, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. L. Fontana, S. Klein, J. O. Holloszy, and B. N. Premachandra, “Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones,” The Journal of Clinical Endocrinology & Metabolism, vol. 91, no. 8, pp. 3232–3235, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Fontana and S. Klein, “Aging, adiposity, and calorie restriction,” Journal of the American Medical Association, vol. 297, no. 9, pp. 986–994, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. J. O. Holloszy and L. Fontana, “Caloric restriction in humans,” Experimental Gerontology, vol. 42, no. 8, pp. 709–712, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. B. J. Willcox, D. C. Willcox, H. Todoriki et al., “Caloric restriction, the traditional okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on morbidity and life span,” Annals of the New York Academy of Sciences, vol. 1114, pp. 434–455, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. L. Fontana, D. T. Villareal, E. P. Weiss et al., “Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial,” American Journal of Physiology, vol. 293, no. 1, pp. E197–E202, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. J. O. Holloszy and L. Fontana, “Caloric restriction in humans,” Experimental Gerontology, vol. 42, no. 8, pp. 709–712, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. T. Hofer, L. Fontana, S. D. Anton et al., “Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans,” Rejuvenation Research, vol. 11, no. 4, pp. 793–799, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. L. M. Redman, J. Rood, S. D. Anton, C. Champagne, S. R. Smith, and E. Ravussin, “Calorie restriction and bone health in young, overweight individuals,” Archives of Internal Medicine, vol. 168, no. 17, pp. 1859–1866, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. C. Cruzen and R. J. Colman, “Effects of caloric restriction on cardiovascular aging in non-human primates and humans,” Clinics in Geriatric Medicine, vol. 25, no. 4, pp. 733–743, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. R. Cangemi, A. J. Friedmann, J. O. Holloszy, and L. Fontana, “Long-term effects of calorie restriction on serum sex-hormone concentrations in men,” Aging Cell, vol. 9, no. 2, pp. 236–242, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. J. F. Trepanowski and R. J. Bloomer, “The impact of religious fasting on human health,” Nutrition Journal, vol. 9, no. 1, article 57, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Soare, R. Cangemi, D. Omodei, J. O. Holloszy, and L. Fontana, “Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans,” Aging, vol. 3, no. 4, pp. 374–379, 2011.
  91. J. Rochon, C. W. Bales, E. Ravussin et al., “Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy,” The Journals of Gerontology A, vol. 66, no. 1, pp. 97–108, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. C. K. Martin, S. K. Das, L. Lindblad et al., “Effect of calorie restriction on the free-living physical activity levels of nonobese humans: results of three randomized trials,” Journal of Applied Physiology, vol. 110, no. 4, pp. 956–963, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. K. Stein, A. Soare, T. E. Meyer, R. Cangemi, J. O. Holloszy, and L. Fontana, “Caloric restriction may reverse age-related autonomic decline in humans,” Aging Cell, vol. 11, no. 4, pp. 644–650, 2012.
  94. R. M. Anderson and R. Weindruch, “Metabolic reprogramming, caloric restriction and aging,” Trends in Endocrinology and Metabolism, vol. 21, no. 3, pp. 134–141, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. J. M. Zahn, S. Poosala, A. B. Owen et al., “AGEMAP: a gene expression database for aging in mice,” PLoS Genetics, vol. 3, no. 11, p. e201, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. J. P. de Magalhães, J. Curado, and G. M. Church, “Meta-analysis of age-related gene expression profiles identifies common signatures of aging,” Bioinformatics, vol. 25, no. 7, pp. 875–881, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. S. K. Park and T. A. Prolla, “Lessons learned from gene expression profile studies of aging and caloric restriction,” Ageing Research Reviews, vol. 4, no. 1, pp. 55–65, 2005. View at Publisher · View at Google Scholar · View at Scopus
  98. G. S. Hotamisligil, “Inflammation and metabolic disorders,” Nature, vol. 444, no. 7121, pp. 860–867, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. F. Lago, C. Dieguez, J. Gómez-Reino, and O. Gualillo, “The emerging role of adipokines as mediators of inflammation and immune responses,” Cytokine & Growth Factor Reviews, vol. 18, no. 3-4, pp. 313–325, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. U. Meier and A. M. Gressner, “Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin,” Clinical Chemistry, vol. 50, no. 9, pp. 1511–1525, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Zhu, G. D. Lee, L. Ding et al., “Adipogenic signaling in rat white adipose tissue: modulation by aging and calorie restriction,” Experimental Gerontology, vol. 42, no. 8, pp. 733–744, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. K. Shinmura, K. Tamaki, K. Saito, Y. Nakano, T. Tobe, and R. Bolli, “Cardioprotective effects of short-term caloric restriction are mediated by adiponectin via activation of AMP-activated protein kinase,” Circulation, vol. 116, no. 24, pp. 2809–2817, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. J. J. Díez and P. Iglesias, “The role of the novel adipocyte-derived hormone adiponectin in human disease,” European Journal of Endocrinology, vol. 148, no. 3, pp. 293–300, 2003. View at Publisher · View at Google Scholar · View at Scopus
  104. O. Ukkola and M. Santaniemi, “Adiponectin: a link between excess adiposity and associated comorbidities?” Journal of Molecular Medicine, vol. 80, no. 11, pp. 696–702, 2002. View at Publisher · View at Google Scholar · View at Scopus
  105. O. Renaldi, B. Pramono, H. Sinorita, L. B. Purnomo, R. H. Asdie, and A. H. Asdie, “Hypoadiponectinemia: a risk factor for metabolic syndrome,” Acta medica Indonesiana, vol. 41, no. 1, pp. 20–24, 2009. View at Scopus
  106. A. E. Civitarese, B. Ukropcova, S. Carling et al., “Role of adiponectin in human skeletal muscle bioenergetics,” Cell Metabolism, vol. 4, no. 1, pp. 75–87, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Nishimura, Y. Izumiya, A. Higuchi et al., “Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase-dependent mechanisms,” Circulation, vol. 117, no. 2, pp. 216–223, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. J. M. Fernández-Real, A. López-Bermejo, R. Casamitjana, and W. Ricart, “Novel interactions of adiponectin with the endocrine system and inflammatory parameters,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 6, pp. 2714–2718, 2003. View at Scopus
  109. W. Aldhahi and O. Hamdy, “Adipokines, inflammation, and the endothelium in diabetes,” Current Diabetes Reports, vol. 3, no. 4, pp. 293–298, 2003. View at Scopus
  110. N. Ouchi, S. Kihara, T. Funahashi, Y. Matsuzawa, and K. Walsh, “Obesity, adiponectin and vascular inflammatory disease,” Current Opinion in Lipidology, vol. 14, no. 6, pp. 561–566, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. D. M. Huffman, D. R. Moellering, W. E. Grizzle, C. R. Stockard, M. S. Johnson, and T. R. Nagy, “Effect of exercise and calorie restriction on biomarkers of aging in mice,” American Journal of Physiology, vol. 294, no. 5, pp. R1618–R1627, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. L. Fontana, E. P. Weiss, D. T. Villareal, S. Klein, and J. O. Holloszy, “Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans,” Aging Cell, vol. 7, no. 5, pp. 681–687, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. A. R. Cameron, S. Anton, L. Melville et al., “Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a,” Aging Cell, vol. 7, no. 1, pp. 69–77, 2008. View at Publisher · View at Google Scholar · View at Scopus
  114. W. Qin, W. Zhao, L. Ho et al., “Regulation of forkhead transcription factor FOXO3a contributes to calorie restriction-induced prevention of Alzheimer's disease-type amyloid neuropathology and spatial memory deterioration,” Annals of the New York Academy of Sciences, vol. 1147, pp. 335–347, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. F. Flachsbart, A. Caliebe, R. Kleindorp et al., “Association of FOX03A variation with human longevity confirmed in German centenarians,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2700–2705, 2009. View at Publisher · View at Google Scholar · View at Scopus
  116. E. J. Anderson, M. E. Lustig, K. E. Boyle et al., “Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans,” The Journal of Clinical Investigation, vol. 119, no. 3, pp. 573–581, 2009. View at Publisher · View at Google Scholar · View at Scopus
  117. D. E. Harrison, R. Strong, Z. D. Sharp et al., “Rapamycin fed late in life extends lifespan in genetically heterogeneous mice,” Nature, vol. 460, no. 7253, pp. 392–395, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. C. Chen, Y. Liu, Y. Liu, and P. Zheng, “mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells,” Science Signaling, vol. 2, no. 98, p. ra75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  119. P. Kapahi, D. Chen, A. N. Rogers et al., “With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging,” Cell Metabolism, vol. 11, no. 6, pp. 453–465, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. B. M. Zid, A. N. Rogers, S. D. Katewa et al., “4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila,” Cell, vol. 139, no. 1, pp. 149–160, 2009. View at Publisher · View at Google Scholar · View at Scopus
  121. S. Sengupta, T. R. Peterson, M. Laplante, S. Oh, and D. M. Sabatini, “mTORC1 controls fasting-induced ketogenesis and its modulation by ageing,” Nature, vol. 468, no. 7327, pp. 1100–1106, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. J. T. Cunningham, J. T. Rodgers, D. H. Arlow, F. Vazquez, V. K. Mootha, and P. Puigserver, “mTOR controls mitochondrial oxidative function through a YY1-PGC-1α transcriptional complex,” Nature, vol. 450, no. 7170, pp. 736–740, 2007. View at Publisher · View at Google Scholar · View at Scopus
  123. A. Ramanathan and S. L. Schreiber, “Direct control of mitochondrial function by mTOR,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 52, pp. 22229–22232, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. J. Knapowski, K. Wieczorowska-Tobis, and J. Witowski, “Pathophysiology of ageing,” Journal of Physiology and Pharmacology, vol. 53, no. 2, pp. 135–146, 2002. View at Scopus
  125. J. P. J. Issa, N. Ahuja, M. Toyota, M. P. Bronner, and T. A. Brentnall, “Accelerated age-related CpG island methylation in ulcerative colitis,” Cancer Research, vol. 61, no. 9, pp. 3573–3577, 2001. View at Scopus
  126. J. P. J. Issa, Y. L. Ottaviano, P. Celano, S. R. Hamilton, N. E. Davidson, and S. B. Baylin, “Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon,” Nature Genetics, vol. 7, no. 4, pp. 536–540, 1994. View at Publisher · View at Google Scholar · View at Scopus
  127. J. P. J. Issa, P. M. Vertino, C. D. Boehm, I. F. Newsham, and S. B. Baylin, “Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 21, pp. 11757–11762, 1996. View at Publisher · View at Google Scholar · View at Scopus
  128. R. P. Singhal, L. L. Mays-Hoopes, and G. L. Eichhorn, “DNA methylation in aging of mice,” Mechanisms of Ageing and Development, vol. 41, no. 3, pp. 199–210, 1987. View at Scopus
  129. T. Waki, G. Tamura, M. Sato, and T. Motoyama, “Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples,” Oncogene, vol. 22, no. 26, pp. 4128–4133, 2003. View at Publisher · View at Google Scholar · View at Scopus
  130. V. L. Wilson, R. A. Smith, S. Ma, and R. G. Cutler, “Genomic 5-methyldeoxycytidine decreases with age,” The Journal of Biological Chemistry, vol. 262, no. 21, pp. 9948–9951, 1987. View at Scopus
  131. T. Y. Kim, H. J. Lee, K. S. Hwang et al., “Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma,” Laboratory Investigation, vol. 84, no. 4, pp. 479–484, 2004. View at Publisher · View at Google Scholar · View at Scopus
  132. Y. Li, M. Daniel, and T. O. Tollefsbol, “Epigenetic regulation of caloric restriction in aging,” BMC Medicine, vol. 9, article 98, 2011.
  133. A. Vaquero and D. Reinberg, “Calorie restriction and the exercise of chromatin,” Genes & Development, vol. 23, no. 16, pp. 1849–1869, 2009. View at Publisher · View at Google Scholar · View at Scopus
  134. U. Muñoz-Najar and J. M. Sedivy, “Epigenetic control of aging,” Antioxidants & Redox Signaling, vol. 14, no. 2, pp. 241–259, 2011. View at Publisher · View at Google Scholar · View at Scopus
  135. B. S. Hass, R. W. Hart, M. H. Lu, and B. D. Lyn-Cook, “Effects of caloric restriction in animals on cellular function, oncogene expression, and DNA methylation in vitro,” Mutation Research, vol. 295, no. 4–6, pp. 281–289, 1993. View at Scopus
  136. Y. Li, L. Liu, and T. O. Tollefsbol, “Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression,” The FASEB Journal, vol. 24, no. 5, pp. 1442–1453, 2010. View at Publisher · View at Google Scholar · View at Scopus
  137. R. S. Ahima, “Connecting obesity, aging and diabetes,” Nature Medicine, vol. 15, no. 9, pp. 996–997, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. T. M. Larsen, S. Dalskov, M. Van Baak et al., “The diet, obesity and genes (diogenes) dietary study in eight European countries—a comprehensive design for long-term intervention,” Obesity Reviews, vol. 11, no. 1, pp. 76–91, 2010. View at Publisher · View at Google Scholar · View at Scopus
  139. F. I. Milagro, J. Campión, P. Cordero et al., “A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss,” The FASEB Journal, vol. 25, no. 4, pp. 1378–1389, 2011. View at Publisher · View at Google Scholar · View at Scopus
  140. L. Bouchard, R. Rabasa-Lhoret, M. Faraj et al., “Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction,” The American Journal of Clinical Nutrition, vol. 91, no. 2, pp. 309–320, 2010. View at Publisher · View at Google Scholar · View at Scopus
  141. J. Campión, F. I. Milagro, E. Goyenechea, and J. A. Martínez, “TNF-α promoter methylation as a predictive biomarker for weight-loss response,” Obesity, vol. 17, no. 6, pp. 1293–1297, 2009. View at Publisher · View at Google Scholar · View at Scopus
  142. A. L. Clayton, C. A. Hazzalin, and L. C. Mahadevan, “Enhanced histone acetylation and transcription: a dynamic perspective,” Molecular Cell, vol. 23, no. 3, pp. 289–296, 2006. View at Publisher · View at Google Scholar · View at Scopus
  143. M. Meyerson, C. M. Counter, E. N. Eaton et al., “hEST2, the putative human telomerase catalytic subunit gene, is up- regulated in tumor cells and during immortalization,” Cell, vol. 90, no. 4, pp. 785–795, 1997. View at Publisher · View at Google Scholar · View at Scopus
  144. T. Kanaya, S. Kyo, M. Takakura, H. Ito, M. Namiki, and M. Inoue, “hTERT is a critical determinant of telomerase activity in renal-cell carcinoma,” International Journal of Cancer, vol. 78, no. 5, pp. 539–543, 1998.
  145. S. J. Lin, P. A. Defossez, and L. Guarente, “Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae,” Science, vol. 289, no. 5487, pp. 2126–2128, 2000. View at Publisher · View at Google Scholar · View at Scopus
  146. L. Guarente and F. Picard, “Calorie restriction—the SIR2 connection,” Cell, vol. 120, no. 4, pp. 473–482, 2005. View at Publisher · View at Google Scholar · View at Scopus
  147. I. B. Leibiger and P. O. Berggren, “Sirt1: a metabolic master switch that modulates lifespan,” Nature Medicine, vol. 12, no. 1, pp. 34–36, 2006. View at Publisher · View at Google Scholar · View at Scopus
  148. L. Bordone, D. Cohen, A. Robinson et al., “SIRT1 transgenic mice show phenotypes resembling calorie restriction,” Aging Cell, vol. 6, no. 6, pp. 759–767, 2007. View at Publisher · View at Google Scholar · View at Scopus
  149. H. Y. Cohen, C. Miller, K. J. Bitterman et al., “Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase,” Science, vol. 305, no. 5682, pp. 390–392, 2004. View at Publisher · View at Google Scholar · View at Scopus
  150. Y. Kanfi, V. Peshti, Y. M. Gozlan, M. Rathaus, R. Gil, and H. Y. Cohen, “Regulation of SIRT1 protein levels by nutrient availability,” FEBS Letters, vol. 582, no. 16, pp. 2417–2423, 2008. View at Publisher · View at Google Scholar · View at Scopus
  151. A. B. Crujeiras, D. Parra, E. Goyenechea, and J. A. Martínez, “Sirtuin gene expression in human mononuclear cells is modulated by caloric restriction,” European Journal of Clinical Investigation, vol. 38, no. 9, pp. 672–678, 2008. View at Publisher · View at Google Scholar · View at Scopus
  152. L. A. Wakeling, L. J. Ions, and D. Ford, “Could Sirt1-mediated epigenetic effects contribute to the longevity response to dietary restriction and be mimicked by other dietary interventions?” Age, vol. 31, no. 4, pp. 327–341, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. Y. Li and T. O. Tollefsbol, “P16INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms,” PLoS ONE, vol. 6, no. 2, Article ID e17421, 2011. View at Publisher · View at Google Scholar · View at Scopus
  154. M. C. Haigis and L. P. Guarente, “Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction,” Genes & Development, vol. 20, no. 21, pp. 2913–2921, 2006. View at Publisher · View at Google Scholar · View at Scopus
  155. J. Luo, A. Y. Nikolaev, S. I. Imai et al., “Negative control of p53 by Sir2α promotes cell survival under stress,” Cell, vol. 107, no. 2, pp. 137–148, 2001. View at Publisher · View at Google Scholar · View at Scopus
  156. E. Langley, M. Pearson, M. Faretta et al., “Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence,” The EMBO Journal, vol. 21, no. 10, pp. 2383–2396, 2002. View at Publisher · View at Google Scholar · View at Scopus
  157. H. Vaziri, S. K. Dessain, E. N. Eaton et al., “hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase,” Cell, vol. 107, no. 2, pp. 149–159, 2001. View at Publisher · View at Google Scholar · View at Scopus
  158. A. Brunet, L. B. Sweeney, J. F. Sturgill et al., “Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase,” Science, vol. 303, no. 5666, pp. 2011–2015, 2004. View at Publisher · View at Google Scholar · View at Scopus
  159. M. C. Motta, N. Divecha, M. Lemieux et al., “Mammalian SIRT1 represses forkhead transcription factors,” Cell, vol. 116, no. 4, pp. 551–563, 2004. View at Publisher · View at Google Scholar · View at Scopus
  160. M. M. Schilling, J. K. Oeser, J. N. Boustead, B. P. Flemming, and R. M. O'Brien, “Gluconeogenesis: re-evaluating the FOXO1-PGC-1α connection,” Nature, vol. 443, no. 7111, pp. E10–E11, 2006. View at Publisher · View at Google Scholar · View at Scopus
  161. R. B. Vega, J. M. Huss, and D. P. Kelly, “The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor α in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes,” Molecular and Cellular Biology, vol. 20, no. 5, pp. 1868–1876, 2000. View at Publisher · View at Google Scholar · View at Scopus
  162. J. Koubova and L. Guarente, “How does calorie restriction work?” Genes & Development, vol. 17, no. 3, pp. 313–321, 2003. View at Publisher · View at Google Scholar · View at Scopus
  163. R. S. Sohal and R. Weindruch, “Oxidative stress, caloric restriction, and aging,” Science, vol. 273, no. 5271, pp. 59–63, 1996. View at Scopus
  164. B. J. Merry, “Molecular mechanisms linking calorie restriction and longevity,” The International Journal of Biochemistry & Cell Biology, vol. 34, no. 11, pp. 1340–1354, 2002. View at Publisher · View at Google Scholar · View at Scopus
  165. J. Jeong, K. Juhn, H. Lee et al., “SIRT1 promotes DNA repair activity and deacetylation of Ku70,” Experimental & Molecular Medicine, vol. 39, no. 1, pp. 8–13, 2007. View at Scopus
  166. H. Y. Cohen, S. Lavu, K. J. Bitterman et al., “Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis,” Molecular Cell, vol. 13, no. 5, pp. 627–638, 2004. View at Publisher · View at Google Scholar · View at Scopus
  167. H. Wong and K. Riabowol, “Differential CDK-inhibitor gene expression in aging human diploid fibroblasts,” Experimental Gerontology, vol. 31, no. 1-2, pp. 311–325, 1996. View at Publisher · View at Google Scholar · View at Scopus
  168. J. Gil and G. Peters, “Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all,” Nature Reviews, vol. 7, no. 9, pp. 667–677, 2006. View at Publisher · View at Google Scholar · View at Scopus
  169. J. Krishnamurthy, C. Torrice, M. R. Ramsey et al., “Ink4a/Arf expression is a biomarker of aging,” The Journal of Clinical Investigation, vol. 114, no. 9, pp. 1299–1307, 2004. View at Publisher · View at Google Scholar · View at Scopus
  170. D. A. Alcorta, Y. Xiong, D. Phelps, G. Hannon, D. Beach, and J. C. Barrett, “Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 24, pp. 13742–13747, 1996. View at Publisher · View at Google Scholar · View at Scopus
  171. A. Melk, B. M. W. Schmidt, O. Takeuchi, B. Sawitzki, D. C. Rayner, and P. F. Halloran, “Expression of p16INK4a and other cell cycle regulator and senescence associated genes in aging human kidney,” Kidney International, vol. 65, no. 2, pp. 510–520, 2004. View at Publisher · View at Google Scholar · View at Scopus
  172. W. Fischle, Y. Wang, and C. D. Allis, “Histone and chromatin cross-talk,” Current Opinion in Cell Biology, vol. 15, no. 2, pp. 172–183, 2003. View at Publisher · View at Google Scholar · View at Scopus
  173. T. Kouzarides, “Histone methylation in transcriptional control,” Current Opinion in Genetics & Development, vol. 12, no. 2, pp. 198–209, 2002. View at Publisher · View at Google Scholar · View at Scopus
  174. N. Noren Hooten, K. Abdelmohsen, M. Gorospe, N. Ejiogu, A. B. Zonderman, and M. K. Evans, “microRNA expression patterns reveal differential expression of target genes with age,” PloS One, vol. 5, no. 5, Article ID e10724, 2010. View at Publisher · View at Google Scholar · View at Scopus
  175. A. De Lencastre, Z. Pincus, K. Zhou, M. Kato, S. S. Lee, and F. J. Slack, “MicroRNAs both promote and antagonize longevity in C. elegans,” Current Biology, vol. 20, no. 24, pp. 2159–2168, 2010. View at Publisher · View at Google Scholar · View at Scopus
  176. D. J. Bates, N. Li, R. Liang et al., “MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging,” Aging Cell, vol. 9, no. 1, pp. 1–18, 2010. View at Publisher · View at Google Scholar · View at Scopus
  177. U. A. Ørom, M. K. Lim, J. E. Savage et al., “MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction,” Cell Cycle, vol. 11, no. 7, pp. 1291–1295, 2012.
  178. A. Khanna, S. Muthusamy, R. Liang, H. Sarojini, and E. Wang, “Gain of survival signaling by down-regulation of three key miRNAs in brain of calorie-restricted mice,” Aging, vol. 3, no. 3, pp. 223–236, 2011.
  179. E. Paradis, H. Douillard, M. Koutroumanis, C. Goodyer, and A. LeBlanc, “Amyloid β peptide of Alzheimer's disease downregulates bcl-2 and upregulates bax expression in human neurons,” Journal of Neuroscience, vol. 16, no. 23, pp. 7533–7539, 1996. View at Scopus
  180. C. Perier, J. Bové, D. C. Wu et al., “Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 19, pp. 8161–8166, 2007. View at Publisher · View at Google Scholar · View at Scopus
  181. N. Louneva, J. W. Cohen, L. Y. Han et al., “Caspase-3 is enriched in postsynaptic densities and increased in Alzheimer's disease,” The American Journal of Pathology, vol. 173, no. 5, pp. 1488–1495, 2008. View at Publisher · View at Google Scholar · View at Scopus
  182. M. Yamada, K. Kida, W. Amutuhaire, F. Ichinose, and M. Kaneki, “Gene disruption of caspase-3 prevents MPTP-induced Parkinson's disease in mice,” Biochemical and Biophysical Research Communications, vol. 402, no. 2, pp. 312–318, 2010. View at Publisher · View at Google Scholar · View at Scopus
  183. W. Kudo, H. P. Lee, M. A. Smith, X. Zhu, S. Matsuyama, and H. G. Lee, “Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity,” Cell Death & Disease, vol. 3, Article ID e309, 2012. View at Publisher · View at Google Scholar
  184. D. K. Ingram, M. Zhu, J. Mamczarz et al., “Calorie restriction mimetics: an emerging research field,” Aging Cell, vol. 5, no. 2, pp. 97–108, 2006. View at Publisher · View at Google Scholar · View at Scopus
  185. H. R. Warner, D. Ingram, R. A. Miller, N. L. Nadon, and A. G. Richardson, “Program for testing biological interventions to promote healthy aging,” Mechanisms of Ageing and Development, vol. 115, no. 3, pp. 199–207, 2000. View at Publisher · View at Google Scholar · View at Scopus
  186. N. L. Nadon, R. Strong, R. A. Miller et al., “Design of aging intervention studies: the NIA interventions testing program,” Age, vol. 30, no. 4, pp. 187–199, 2008. View at Publisher · View at Google Scholar · View at Scopus
  187. R. A. Miller, D. E. Harrison, C. M. Astle et al., “An aging interventions testing program: study design and interim report,” Aging Cell, vol. 6, no. 4, pp. 565–575, 2007. View at Publisher · View at Google Scholar · View at Scopus
  188. R. Strong, R. A. Miller, C. M. Astle et al., “Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice,” Aging Cell, vol. 7, no. 5, pp. 641–650, 2008. View at Publisher · View at Google Scholar · View at Scopus
  189. N. L. Nadon, “Exploiting the rodent model for studies on the pharmacology of lifespan extension,” Aging Cell, vol. 5, no. 1, pp. 9–15, 2006. View at Publisher · View at Google Scholar · View at Scopus
  190. J. O. Holloszy, “Mortality rate and longevity of food-restricted exercising male rats: a reevaluation,” Journal of Applied Physiology, vol. 82, no. 2, pp. 399–403, 1997. View at Scopus
  191. K. C. Deruisseau, A. N. Kavazis, S. Judge et al., “Moderate caloric restriction increases diaphragmatic antioxidant enzyme mRNA, but not when combined with lifelong exercise,” Antioxidants & Redox Signaling, vol. 8, no. 3-4, pp. 539–547, 2006. View at Publisher · View at Google Scholar · View at Scopus
  192. A. Y. Seo, T. Hofer, B. Sung, S. Judge, H. Y. Chung, and C. Leeuwenburgh, “Hepatic oxidative stress during aging: effects of 8% long-term calorie restriction and lifelong exercise,” Antioxidants & Redox Signaling, vol. 8, no. 3-4, pp. 529–538, 2006. View at Publisher · View at Google Scholar · View at Scopus
  193. R. Kalani, S. Judge, C. Carter, M. Pahor, and C. Leeuwenburgh, “Effects of caloric restriction and exercise on age-related, chronic inflammation assessed by C-reactive protein and interleukin-6,” The Journals of Gerontology A, vol. 61, no. 3, pp. 211–217, 2006. View at Scopus
  194. P. Abete, G. Testa, G. Galizia et al., “Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart,” Experimental Gerontology, vol. 40, no. 1-2, pp. 43–50, 2005. View at Publisher · View at Google Scholar · View at Scopus
  195. D. L. Crandall, R. P. Feirer, D. R. Griffith, and D. C. Beitz, “Relative role of caloric restriction and exercise training upon susceptibility to isoproterenol-induced myocardial infarction in male rats,” The American Journal of Clinical Nutrition, vol. 34, no. 5, pp. 841–847, 1981. View at Scopus
  196. A. E. Civitarese, S. Carling, L. K. Heilbronn et al., “Calorie restriction increases muscle mitochondrial biogenesis in healthy humans,” PLoS Medicine, vol. 4, no. 3, article e76, 2007. View at Publisher · View at Google Scholar · View at Scopus
  197. D. E. Larson-Meyer, B. R. Newcomer, L. K. Heilbronn et al., “Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function,” Obesity, vol. 16, no. 6, pp. 1355–1362, 2008. View at Publisher · View at Google Scholar · View at Scopus
  198. M. Lefevre, L. M. Redman, L. K. Heilbronn et al., “Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals,” Atherosclerosis, vol. 203, no. 1, pp. 206–213, 2009. View at Publisher · View at Google Scholar · View at Scopus
  199. D. E. Larson-Meyer, L. Redman, L. K. Heilbronn, C. K. Martin, and E. Ravussin, “Caloric restriction with or without exercise: the fitness versus fatness debate,” Medicine and Science in Sports and Exercise, vol. 42, no. 1, pp. 152–159, 2010. View at Publisher · View at Google Scholar · View at Scopus
  200. N. E. Silverman, B. J. Nicklas, and A. S. Ryan, “Addition of aerobic exercise to a weight loss program increases BMD, with an associated reduction in inflammation in overweight postmenopausal women,” Calcified Tissue International, vol. 84, no. 4, pp. 257–265, 2009. View at Publisher · View at Google Scholar · View at Scopus
  201. J. F. Trepanowski, R. E. Canale, K. E. Marshall, M. M. Kabir, and R. J. Bloomer, “Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings,” Nutrition Journal, vol. 10, article 107, 2011.
  202. K. Iwasaki, C. A. Gleiser, E. J. Masoro, C. A. McMahan, E. Seo, and B. P. Yu, “The influence of dietary protein source on longevity and age-related disease processes of Fischer rats,” Journals of Gerontology, vol. 43, no. 1, pp. B5–B12, 1988. View at Scopus
  203. I. Shimokawa, Y. Higami, B. P. Yu, E. J. Masoro, and T. Ikeda, “Influence of dietary components on occurrence of and mortality due to neoplasms in male F344 rats,” Aging, vol. 8, no. 4, pp. 254–262, 1996. View at Scopus
  204. M. Khorakova, Z. Deil, D. Khausman, and K. Matsek, “Effect of carbohydrate-enriched diet and subsequent food restriction on life prolongation in Fischer 344 male rats,” Fiziologicheskii Zhurnal, vol. 36, no. 5, pp. 16–21, 1990. View at Scopus
  205. C. Kubo, B. C. Johnson, A. Gajjar, and R. A. Good, “Crucial dietary factors in maximizing life span and longevity in autoimmune-prone mice,” The Journal of Nutrition, vol. 117, no. 6, pp. 1129–1135, 1987. View at Scopus
  206. R. Pamplona and G. Barja, “Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection,” Biochimica et Biophysica Acta, vol. 1757, no. 5-6, pp. 496–508, 2006. View at Publisher · View at Google Scholar · View at Scopus
  207. A. Sanz, P. Caro, J. G. Sanchez, and G. Barja, “Effect of lipid restriction on mitochondrial free radical production and oxidative DNA damage,” Annals of the New York Academy of Sciences, vol. 1067, no. 1, pp. 200–209, 2006. View at Publisher · View at Google Scholar · View at Scopus
  208. A. Sanz, J. Gómez, P. Caro, and G. Barja, “Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage,” Journal of Bioenergetics and Biomembranes, vol. 38, no. 5-6, pp. 327–333, 2006. View at Publisher · View at Google Scholar · View at Scopus
  209. P. E. Segall and P. S. Timiras, “Pathophysiologic findings after chronic tryptophan deficiency in rats: a model for delayed growth and aging,” Mechanisms of Ageing and Development, vol. 5, no. 2, pp. 109–124, 1976. View at Scopus
  210. H. Ooka, P. E. Segall, and P. S. Timiras, “Histology and survival in age-delayed low-tryptophan-fed rats,” Mechanisms of Ageing and Development, vol. 43, no. 1, pp. 79–98, 1988. View at Scopus
  211. R. A. Miller, G. Buehner, Y. Chang, J. M. Harper, R. Sigler, and M. Smith-Wheelock, “Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance,” Aging Cell, vol. 4, no. 3, pp. 119–125, 2005. View at Publisher · View at Google Scholar · View at Scopus
  212. N. Orentreich, J. R. Matias, A. DeFelice, and J. A. Zimmerman, “Low methionine ingestion by rats extends life span,” The Journal of Nutrition, vol. 123, no. 2, pp. 269–274, 1993. View at Scopus
  213. J. P. Richie Jr., Y. Leutzinger, S. Parthasarathy, V. Malloy, N. Orentreich, and J. A. Zimmerman, “Methionine restriction increases blood glutathione and longevity in F344 rats,” The FASEB Journal, vol. 8, no. 15, pp. 1302–1307, 1994. View at Scopus
  214. J. P. Richie Jr., D. Komninou, Y. Leutzinger et al., “Tissue glutathione and cysteine levels in methionine-restricted rats,” Nutrition, vol. 20, no. 9, pp. 800–805, 2004. View at Publisher · View at Google Scholar · View at Scopus
  215. J. A. Zimmerman, V. Malloy, R. Krajcik, and N. Orentreich, “Nutritional control of aging,” Experimental Gerontology, vol. 38, no. 1-2, pp. 47–52, 2003. View at Publisher · View at Google Scholar · View at Scopus
  216. A. Sanz, P. Caro, V. Ayala, M. Portero-Otin, R. Pamplona, and G. Barja, “Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins,” The FASEB Journal, vol. 20, no. 8, pp. 1064–1073, 2006. View at Publisher · View at Google Scholar · View at Scopus
  217. P. Caro, J. Gómez, M. López-Torres et al., “Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver,” Biogerontology, vol. 9, no. 3, pp. 183–196, 2008. View at Publisher · View at Google Scholar · View at Scopus
  218. M. C. Ruiz, V. Ayala, M. Portero-Otín, J. R. Requena, G. Barja, and R. Pamplona, “Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals,” Mechanisms of Ageing and Development, vol. 126, no. 10, pp. 1106–1114, 2005. View at Publisher · View at Google Scholar · View at Scopus
  219. N. Hidiroglou, G. S. Gilani, L. Long et al., “The influence of dietary vitamin E, fat, and methionine on blood cholesterol profile, homocysteine levels, and oxidizability of low density lipoprotein in the gerbil,” The Journal of Nutritional Biochemistry, vol. 15, no. 12, pp. 730–740, 2004. View at Publisher · View at Google Scholar · View at Scopus
  220. P. Caro, J. Gomez, I. Sanchez et al., “Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver,” Biogerontology, vol. 10, no. 5, pp. 579–592, 2009. View at Publisher · View at Google Scholar · View at Scopus
  221. M. F. McCarty, J. Barroso-Aranda, and F. Contreras, “The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy,” Medical Hypotheses, vol. 72, no. 2, pp. 125–128, 2009. View at Publisher · View at Google Scholar · View at Scopus
  222. K. A. Varady and M. K. Hellerstein, “Alternate-day fasting and chronic disease prevention: a review of human and animal trials,” The American Journal of Clinical Nutrition, vol. 86, no. 1, pp. 7–13, 2007. View at Scopus
  223. R. M. Anson, Z. Guo, R. de Cabo et al., “Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 10, pp. 6216–6220, 2003. View at Publisher · View at Google Scholar · View at Scopus
  224. O. Descamps, J. Riondel, V. Ducros, and A. M. Roussel, “Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting,” Mechanisms of Ageing and Development, vol. 126, no. 11, pp. 1185–1191, 2005. View at Publisher · View at Google Scholar · View at Scopus
  225. W. Duan, Z. Guo, H. Jiang, M. Ware, and M. P. Mattson, “Reversal of behavioral and metabolic abnormalities, and insulin resistance syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic factor,” Endocrinology, vol. 144, no. 6, pp. 2446–2453, 2003. View at Publisher · View at Google Scholar · View at Scopus
  226. I. Ahmet, R. Wan, M. P. Mattson, E. G. Lakatta, and M. Talan, “Cardioprotection by intermittent fasting in rats,” Circulation, vol. 112, no. 20, pp. 3115–3121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  227. D. E. Mager, R. Wan, M. Brown et al., “Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats,” The FASEB Journal, vol. 20, no. 6, pp. 631–637, 2006. View at Publisher · View at Google Scholar · View at Scopus
  228. C. R. Pedersen, I. Hagemann, T. Bock, and K. Buschard, “Intermittent feeding and fasting reduces diabetes incidence in BB rats,” Autoimmunity, vol. 30, no. 4, pp. 243–250, 1999. View at Scopus
  229. K. Tikoo, D. N. Tripathi, D. G. Kabra, V. Sharma, and A. B. Gaikwad, “Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53,” FEBS Letters, vol. 581, no. 5, pp. 1071–1078, 2007. View at Publisher · View at Google Scholar · View at Scopus
  230. R. Wan, S. Camandola, and M. P. Mattson, “Intermittent fasting and dietary supplementation with 2-deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats,” The FASEB Journal, vol. 17, no. 9, pp. 1133–1134, 2003. View at Scopus
  231. L. K. Heilbronn, S. R. Smith, C. K. Martin, S. D. Anton, and E. Ravussin, “Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism,” The American Journal of Clinical Nutrition, vol. 81, no. 1, pp. 69–73, 2005. View at Scopus
  232. N. Halberg, M. Henriksen, N. Söderhamn et al., “Effect of intermittent fasting and refeeding on insulin action in healthy men,” Journal of Applied Physiology, vol. 99, no. 6, pp. 2128–2136, 2005. View at Publisher · View at Google Scholar · View at Scopus
  233. J. B. Johnson, W. Summer, R. G. Cutler et al., “Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma,” Free Radical Biology and Medicine, vol. 42, no. 5, pp. 665–674, 2007. View at Publisher · View at Google Scholar · View at Scopus
  234. V. D. Dixit, H. Yang, K. S. Sayeed et al., “Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production,” Journal of Inflammation, vol. 8, article 6, 2011. View at Publisher · View at Google Scholar · View at Scopus
  235. K. T. Howitz, K. J. Bitterman, H. Y. Cohen et al., “Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan,” Nature, vol. 425, no. 6954, pp. 191–196, 2003. View at Publisher · View at Google Scholar · View at Scopus
  236. J. G. Wood, B. Rogina, S. Lavu, et al., “Sirtuin activators mimic caloric restriction and delay ageing in metazoans,” Nature, vol. 430, no. 7000, pp. 686–689, 2004.
  237. H. Yang, J. A. Baur, A. Chen, C. Miller, and D. A. Sinclair, “Design and synthesis of compounds that extend yeast replicative lifespan,” Aging Cell, vol. 6, no. 1, pp. 35–43, 2007. View at Publisher · View at Google Scholar · View at Scopus
  238. D. R. Valenzano, E. Terzibasi, T. Genade, A. Cattaneo, L. Domenici, and A. Cellerino, “Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate,” Current Biology, vol. 16, no. 3, pp. 296–300, 2006. View at Publisher · View at Google Scholar · View at Scopus
  239. M. Kaeberlein, T. McDonagh, B. Heltweg et al., “Substrate-specific activation of sirtuins by resveratrol,” The Journal of Biological Chemistry, vol. 280, no. 17, pp. 17038–17045, 2005. View at Publisher · View at Google Scholar · View at Scopus
  240. M. Kaeberlein and R. W. Powers III, “Sir2 and calorie restriction in yeast: a skeptical perspective,” Ageing Research Reviews, vol. 6, no. 2, pp. 128–140, 2007. View at Publisher · View at Google Scholar · View at Scopus
  241. M. Kaeberlein and B. K. Kennedy, “Does resveratrol activate yeast Sir2 in vivo?” Aging Cell, vol. 6, no. 4, pp. 415–416, 2007. View at Publisher · View at Google Scholar · View at Scopus
  242. D. L. Smith Jr., C. Li, M. Matecic, N. Maqani, M. Bryk, and J. S. Smith, “Calorie restriction effects on silencing and recombination at the yeast rDNA,” Aging Cell, vol. 8, no. 6, pp. 633–642, 2009. View at Publisher · View at Google Scholar · View at Scopus
  243. T. M. Bass, D. Weinkove, K. Houthoofd, D. Gems, and L. Partridge, “Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans,” Mechanisms of Ageing and Development, vol. 128, no. 10, pp. 546–552, 2007. View at Publisher · View at Google Scholar · View at Scopus
  244. E. L. Greer and A. Brunet, “Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans,” Aging Cell, vol. 8, no. 2, pp. 113–127, 2009. View at Publisher · View at Google Scholar · View at Scopus
  245. T. L. Kaeberlein, E. D. Smith, M. Tsuchiya et al., “Lifespan extension in Caenorhabditis elegans by complete removal of food,” Aging Cell, vol. 5, no. 6, pp. 487–494, 2006. View at Publisher · View at Google Scholar · View at Scopus
  246. S. Zou, J. R. Carey, P. Liedo et al., “The prolongevity effect of resveratrol depends on dietary composition and calorie intake in a tephritid fruit fly,” Experimental Gerontology, vol. 44, no. 6-7, pp. 472–476, 2009. View at Publisher · View at Google Scholar · View at Scopus
  247. M. Riesen and A. Morgan, “Calorie restriction reduces rDNA recombination independently of rDNA silencing,” Aging Cell, vol. 8, no. 6, pp. 624–632, 2009. View at Publisher · View at Google Scholar · View at Scopus
  248. M. Pacholec, J. E. Bleasdale, B. Chrunyk et al., “SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1,” The Journal of Biological Chemistry, vol. 285, no. 11, pp. 8340–8351, 2010. View at Publisher · View at Google Scholar · View at Scopus
  249. J. A. Baur, K. J. Pearson, N. L. Price et al., “Resveratrol improves health and survival of mice on a high-calorie diet,” Nature, vol. 444, no. 7117, pp. 337–342, 2006. View at Publisher · View at Google Scholar · View at Scopus
  250. M. Zang, S. Xu, K. A. Maitland-Toolan et al., “Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice,” Diabetes, vol. 55, no. 8, pp. 2180–2191, 2006. View at Publisher · View at Google Scholar · View at Scopus
  251. B. Dasgupta and J. Milbrandt, “Resveratrol stimulates AMP kinase activity in neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 17, pp. 7217–7222, 2007. View at Publisher · View at Google Scholar · View at Scopus
  252. N. L. Price, A. P. Gomes, A. J. Ling, et al., “SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function,” Cell Metabolism, vol. 15, no. 5, pp. 675–690, 2012.
  253. J. L. Barger, T. Kayo, J. M. Vann et al., “A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice,” PLoS ONE, vol. 3, no. 6, Article ID e2264, 2008. View at Publisher · View at Google Scholar · View at Scopus
  254. K. J. Pearson, J. A. Baur, K. N. Lewis et al., “Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span,” Cell Metabolism, vol. 8, no. 2, pp. 157–168, 2008. View at Publisher · View at Google Scholar · View at Scopus
  255. R. A. Miller, D. E. Harrison, C. M. Astle et al., “Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice,” The Journals of Gerontology A, vol. 66, no. 2, pp. 191–201, 2011. View at Publisher · View at Google Scholar · View at Scopus
  256. D. L. Smith Jr., T. R. Nagy, and D. B. Allison, “Calorie restriction: what recent results suggest for the future of ageing research,” European Journal of Clinical Investigation, vol. 40, no. 5, pp. 440–450, 2010. View at Publisher · View at Google Scholar · View at Scopus
  257. A. Dal-Pan, S. Blanc, and F. Aujard, “Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity,” BMC Physiology, vol. 10, no. 1, article 11, 2010. View at Publisher · View at Google Scholar · View at Scopus
  258. A. Dal-Pan, J. Terrien, F. Pifferi et al., “Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus,” Age, vol. 33, no. 1, pp. 15–31, 2011. View at Publisher · View at Google Scholar · View at Scopus
  259. L. Peltz, J. Gomez, M. Marquez, et al., “Resveratrol exerts dosage and duration dependent effect on human mesenchymal stem cell development,” PLoS One, vol. 7, no. 5, Article ID e37162, 2012.
  260. J. Mikuła-Pietrasik, A. Kuczmarska, B. Rubiś, et al., “Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms,” Free Radical Biology & Medicine, vol. 52, pp. 2234–2245, 2012.
  261. J. M. Smoliga, J. A. Baur, and H. A. Hausenblas, “Resveratrol and health—a comprehensive review of human clinical trials,” Molecular Nutrition & Food Research, vol. 55, no. 8, pp. 1129–1141, 2011. View at Publisher · View at Google Scholar · View at Scopus
  262. H. Ghanim, C. L. Sia, S. Abuaysheh et al., “An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol,” The Journal of Clinical Endocrinology & Metabolism, vol. 95, no. 9, pp. E1–E8, 2010. View at Publisher · View at Google Scholar · View at Scopus
  263. H. Ghanim, S. Abuaysheh, C. L. Sia et al., “Increase in plasma endotoxin concentrations and the expression of toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance,” Diabetes Care, vol. 32, no. 12, pp. 2281–2287, 2009. View at Publisher · View at Google Scholar · View at Scopus
  264. H. Ghanim, C. L. Sia, K. Korzeniewski et al., “A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal,” The Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 5, pp. 1409–1414, 2011. View at Publisher · View at Google Scholar · View at Scopus
  265. P. Brasnyó, G. A. Molnár, M. Mohás, et al., “Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients,” The British Journal of Nutrition, vol. 106, no. 3, pp. 383–389, 2011.
  266. L. M. Vislocky and M. L. Fernandez, “Biomedical effects of grape products,” Nutrition Reviews, vol. 68, no. 11, pp. 656–670, 2010. View at Publisher · View at Google Scholar · View at Scopus
  267. A. A. A. Bertelli and D. K. Das, “Grapes, wines, resveratrol, and heart health,” Journal of Cardiovascular Pharmacology, vol. 54, no. 6, pp. 468–476, 2009. View at Publisher · View at Google Scholar · View at Scopus
  268. M. M. Dohadwala and J. A. Vita, “Grapes and cardiovascular disease,” The Journal of Nutrition, vol. 139, no. 9, pp. 17885–17935, 2009. View at Publisher · View at Google Scholar · View at Scopus
  269. W. R. Leifert and M. Y. Abeywardena, “Grape seed and red wine polyphenol extracts inhibit cellular cholesterol uptake, cell proliferation, and 5-lipoxygenase activity,” Nutrition Research, vol. 28, no. 11, pp. 729–737, 2008. View at Publisher · View at Google Scholar · View at Scopus
  270. T. Wallerath, G. Deckert, T. Ternes et al., “Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase,” Circulation, vol. 106, no. 13, pp. 1652–1658, 2002. View at Publisher · View at Google Scholar · View at Scopus
  271. T. Wallerath, H. Li, U. Gödtel-Ambrust, P. M. Schwarz, and U. Förstermann, “A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase,” Nitric Oxide, vol. 12, no. 2, pp. 97–104, 2005. View at Publisher · View at Google Scholar · View at Scopus
  272. J. F. Leikert, T. R. Räthel, P. Wohlfart, V. Cheynier, A. M. Vollmar, and V. M. Dirsch, “Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells,” Circulation, vol. 106, no. 13, pp. 1614–1617, 2002. View at Publisher · View at Google Scholar · View at Scopus
  273. P. Gresele, P. Pignatelli, G. Guglielmini et al., “Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production,” The Journal of Nutrition, vol. 138, no. 9, pp. 1602–1608, 2008. View at Scopus
  274. D. O. Kennedy, E. L. Wightman, J. L. Reay et al., “Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation,” The American Journal of Clinical Nutrition, vol. 91, no. 6, pp. 1590–1597, 2010. View at Publisher · View at Google Scholar · View at Scopus
  275. R. H. X. Wong, P. R. C. Howe, J. D. Buckley, A. M. Coates, I. Kunz, and N. M. Berry, “Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 21, no. 11, pp. 851–856, 2011. View at Publisher · View at Google Scholar · View at Scopus
  276. B. Agarwal and J. A. Baur, “Resveratrol and life extension,” Annals of the New York Academy of Sciences, vol. 1215, no. 1, pp. 138–143, 2011. View at Publisher · View at Google Scholar · View at Scopus
  277. J. L. Crespo and M. N. Hall, “Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae,” Microbiology and Molecular Biology Reviews, vol. 66, no. 4, pp. 579–591, 2002. View at Publisher · View at Google Scholar · View at Scopus
  278. I. Bjedov, J. M. Toivonen, F. Kerr et al., “Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster,” Cell Metabolism, vol. 11, no. 1, pp. 35–46, 2010. View at Publisher · View at Google Scholar · View at Scopus
  279. N. Anisimov, M. A. Zabezhinski, I. G. Popovich, et al., “Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice,” Cell Cycle, vol. 10, no. 24, pp. 4230–4236, 2011. View at Publisher · View at Google Scholar
  280. S. Majumder, A. Caccamo, D. X. Medina, et al., “Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1β and enhancing NMDA signaling,” Aging Cell, vol. 11, no. 2, pp. 326–335, 2012. View at Publisher · View at Google Scholar
  281. G. Payne, A. Laporte, R. Deber, and P. C. Coyte, “Counting backward to health care's future: using time-to-death modeling to identify changes in end-of-life morbidity and the impact of aging on health care expenditures,” The Milbank Quarterly, vol. 85, no. 2, pp. 213–257, 2007. View at Publisher · View at Google Scholar · View at Scopus
  282. A. Yazdanyar and A. B. Newman, “The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs,” Clinics in Geriatric Medicine, vol. 25, no. 4, pp. 563–577, 2009. View at Publisher · View at Google Scholar · View at Scopus
  283. J. Mesterton, A. Wimo, Å. By, S. Langworth, B. Winblad, and L. Jönsson, “Cross sectional observational study on the societal costs of Alzheimer's disease,” Current Alzheimer Research, vol. 7, no. 4, pp. 358–367, 2010. View at Publisher · View at Google Scholar · View at Scopus
  284. G. Atzmon, C. Schechter, W. Greiner, D. Davidson, G. Rennert, and N. Barzilai, “Clinical phenotype of families with longevity,” Journal of the American Geriatrics Society, vol. 52, no. 2, pp. 274–277, 2004. View at Publisher · View at Google Scholar · View at Scopus
  285. G. Atzmon, M. Rincon, P. Rabizadeh, and N. Barzilai, “Biological evidence for inheritance of exceptional longevity,” Mechanisms of Ageing and Development, vol. 126, no. 2, pp. 341–345, 2005. View at Publisher · View at Google Scholar · View at Scopus
  286. N. Barzilai and I. Gabriely, “Genetic studies reveal the role of the endocrine and metabolic systems in aging,” The Journal of Clinical Endocrinology & Metabolism, vol. 95, no. 10, pp. 4493–4500, 2010. View at Publisher · View at Google Scholar · View at Scopus
  287. M. C. Haigis and B. A. Yankner, “The aging stress response,” Molecular Cell, vol. 40, no. 2, pp. 333–344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  288. D. Nipič, A. Pirc, B. Banič, D. Šuput, and I. Milisav, “Preapoptotic cell stress response of primary hepatocytes,” Hepatology, vol. 51, no. 6, pp. 2140–2151, 2010. View at Publisher · View at Google Scholar · View at Scopus