Advertisement

Mammalian Genome

, Volume 27, Issue 7–8, pp 300–319 | Cite as

Caloric restriction: beneficial effects on brain aging and Alzheimer’s disease

  • Caroline Van Cauwenberghe
  • Charysse Vandendriessche
  • Claude Libert
  • Roosmarijn E. Vandenbroucke
Article

Abstract

Dietary interventions such as caloric restriction (CR) extend lifespan and health span. Recent data from animal and human studies indicate that CR slows down the aging process, benefits general health, and improves memory performance. Caloric restriction also retards and slows down the progression of different age-related diseases, such as Alzheimer’s disease. However, the specific molecular basis of these effects remains unclear. A better understanding of the pathways underlying these effects could pave the way to novel preventive or therapeutic strategies. In this review, we will discuss the mechanisms and effects of CR on aging and Alzheimer’s disease. A potential alternative to CR as a lifestyle modification is the use of CR mimetics. These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. We discuss the effect of two of the most investigated mimetics, resveratrol and rapamycin, on aging and their potential as Alzheimer’s disease therapeutics. However, additional research will be needed to determine the safety, efficacy, and usability of CR and its mimetics before a general recommendation can be proposed to implement them.

Keywords

Metformin Amyotrophic Lateral Sclerosis Resveratrol Rapamycin Caloric Restriction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by the Research Council of Ghent University, the Belgian Foundation of Alzheimer’s Research (SAO), and the Research Foundation Flanders (FWO Vlaanderen). We thank Dr. Amin Bredan for careful editing of the manuscript.

References

  1. Adams MM, Shi L, Linville MC, Forbes ME, Long AB, Bennett C, Newton IG, Carter CS, Sonntag WE, Riddle DR, Brunso-Bechtold JK (2008) Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability. Exp Neurol 211(1):141–149PubMedPubMedCentralCrossRefGoogle Scholar
  2. Albert V, Hall MN (2015) mTOR signaling in cellular and organismal energetics. Curr Opin Cell Biol 33:55–66PubMedCrossRefGoogle Scholar
  3. Anisimov VN, Bartke A (2013) The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol 87:201–223PubMedPubMedCentralCrossRefGoogle Scholar
  4. Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Rosenfeld SV, Blagosklonny MV (2011) Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle 10:4230–4236PubMedCrossRefGoogle Scholar
  5. Armentero MT, Levandis G, Bramanti P, Nappi G, Blandini F (2008) Dietary restriction does not prevent nigrostriatal degeneration in the 6-hydroxydopamine model of Parkinson’s disease. Exp Neurol 212:548–551PubMedCrossRefGoogle Scholar
  6. Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA (2008) A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One 3:e2264PubMedPubMedCentralCrossRefGoogle Scholar
  7. Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581PubMedGoogle Scholar
  8. Bekinschtein P, Oomen CA, Saksida LM, Bussey TJ (2011) Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol 22:536–542PubMedCrossRefGoogle Scholar
  9. Bellaver B, Souza DG, Souza DO, Quincozes-Santos A (2014) Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats. Toxicol In Vitro 28:479–484PubMedCrossRefGoogle Scholar
  10. Boland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, Nixon RA (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci 28:6926–6937PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, Steele AD, Crowe H, Marmor S, Luo J, Gu W, Guarente L (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6:759–767PubMedCrossRefGoogle Scholar
  12. Brachmann CB, Sherman JM, Devine SE, Cameron EE, Pillus L, Boeke JD (1995) The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability. Genes Dev 9:2888–2902PubMedCrossRefGoogle Scholar
  13. Brownlow ML, Joly-Amado A, Azam S, Elza M, Selenica ML, Pappas C, Small B, Engelman R, Gordon MN, Morgan D (2014) Partial rescue of memory deficits induced by calorie restriction in a mouse model of tau deposition. Behav Brain Res 271:79–88PubMedCrossRefGoogle Scholar
  14. Caccamo A, Majumder S, Richardson A, Strong R, Oddo S (2010) Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem 285:13107–13120PubMedPubMedCentralCrossRefGoogle Scholar
  15. Caccamo A, Magri A, Medina DX, Wisely EV, Lopez-Aranda MF, Silva AJ, Oddo S (2013) mTOR regulates tau phosphorylation and degradation: implications for Alzheimer’s disease and other tauopathies. Aging Cell 12:370–380PubMedPubMedCentralCrossRefGoogle Scholar
  16. Calvert S, Tacutu R, Sharifi S, Teixeira R, Ghosh P, de Magalhaes JP (2016) A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans. Aging Cell 15:256–266PubMedCrossRefGoogle Scholar
  17. Canto C, Auwerx J (2011) Calorie restriction: is AMPK a key sensor and effector? Physiology (Bethesda) 26:214–224CrossRefGoogle Scholar
  18. Cava E, Fontana L (2013) Will calorie restriction work in humans? Aging (Albany NY) 5:507–514CrossRefGoogle Scholar
  19. Chan MF, Liang G, Jones PA (2000) Relationship between transcription and DNA methylation. Curr Top Microbiol Immunol 249:75–86PubMedGoogle Scholar
  20. Chen C, Liu Y, Liu Y, Zheng P (2009a) mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2:75Google Scholar
  21. Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF (2009b) Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci USA 106:3907–3912PubMedPubMedCentralCrossRefGoogle Scholar
  22. Chin D, Huebbe P, Pallauf K, Rimbach G (2013) Neuroprotective properties of curcumin in Alzheimer’s disease–merits and limitations. Curr Med Chem 20:3955–3985PubMedCrossRefGoogle Scholar
  23. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305:390–392PubMedCrossRefGoogle Scholar
  24. Colman RJ, Beasley TM, Allison DB, Weindruch R (2008) Attenuation of sarcopenia by dietary restriction in rhesus monkeys. J Gerontol A Biol Sci Med Sci 63:556–559PubMedPubMedCentralCrossRefGoogle Scholar
  25. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201–204PubMedPubMedCentralCrossRefGoogle Scholar
  26. Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM (2014) Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5:3557PubMedPubMedCentralCrossRefGoogle Scholar
  27. Craft S, Cholerton B, Baker LD (2013) Insulin and Alzheimer’s disease: untangling the web. J Alzheimers Dis 33(Suppl 1):S263–S275PubMedGoogle Scholar
  28. Cuervo AM (2008) Autophagy and aging: keeping that old broom working. Trends Genet 24:604–612PubMedPubMedCentralCrossRefGoogle Scholar
  29. da Luz PL, Tanaka L, Brum PC, Dourado PM, Favarato D, Krieger JE, Laurindo FR (2012) Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. Atherosclerosis 224:136–142PubMedCrossRefGoogle Scholar
  30. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749PubMedPubMedCentralCrossRefGoogle Scholar
  31. Dhahbi JM, Mote PL, Fahy GM, Spindler SR (2005) Identification of potential caloric restriction mimetics by microarray profiling. Physiol Genom 23:343–350CrossRefGoogle Scholar
  32. Duan W, Mattson MP (1999) Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson’s disease. J Neurosci Res 57:195–206PubMedCrossRefGoogle Scholar
  33. Duan W, Lee J, Guo Z, Mattson MP (2001) Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury. J Mol Neurosci 16:1–12PubMedCrossRefGoogle Scholar
  34. Duan W, Guo Z, Jiang H, Ware M, Li XJ, Mattson MP (2003) Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci USA 100:2911–2916PubMedPubMedCentralCrossRefGoogle Scholar
  35. Elshorbagy AK, Valdivia-Garcia M, Mattocks DA, Plummer JD, Orentreich DS, Orentreich N, Refsum H, Perrone CE (2013) Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance. Metabolism 62:509–517PubMedCrossRefGoogle Scholar
  36. Feng X, Liang N, Zhu D, Gao Q, Peng L, Dong H, Yue Q, Liu H, Bao L, Zhang J, Hao J, Gao Y, Yu X, Sun J (2013) Resveratrol inhibits beta-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway. PLoS One 8:e59888PubMedPubMedCentralCrossRefGoogle Scholar
  37. Finkel T (2015) The metabolic regulation of aging. Nat Med 21:1416–1423PubMedCrossRefGoogle Scholar
  38. Flynn JM, O’Leary MN, Zambataro CA, Academia EC, Presley MP, Garrett BJ, Zykovich A, Mooney SD, Strong R, Rosen CJ, Kapahi P, Nelson MD, Kennedy BK, Melov S (2013) Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell 12:851–862PubMedPubMedCentralCrossRefGoogle Scholar
  39. Fok WC, Chen Y, Bokov A, Zhang Y, Salmon AB, Diaz V, Javors M, Wood WH 3rd, Zhang Y, Becker KG, Perez VI, Richardson A (2014) Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome. PLoS One 9:e83988PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span–from yeast to humans. Science 328:321–326PubMedPubMedCentralCrossRefGoogle Scholar
  41. Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 102:1095–1104PubMedCrossRefGoogle Scholar
  42. Gillette-Guyonnet S, Secher M, Vellas B (2013) Nutrition and neurodegeneration: epidemiological evidence and challenges for future research. Br J Clin Pharmacol 75:738–755PubMedPubMedCentralCrossRefGoogle Scholar
  43. Goldberg EL, Romero-Aleshire MJ, Renkema KR, Ventevogel MS, Chew WM, Uhrlaub JL, Smithey MJ, Limesand KH, Sempowski GD, Brooks HL, Nikolich-Zugich J (2015) Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms. Aging Cell 14:130–138PubMedCrossRefGoogle Scholar
  44. Gorlé N, Van Cauwenberghe C, Libert C, Vandenbroucke RE (2016) The effect of aging on brain barriers and the consequences for Alzheimer's disease development. Mamm Genome. doi: 10.1007/s00335-016-9637-8 Google Scholar
  45. Goto S, Takahashi R, Radak Z, Sharma R (2007) Beneficial biochemical outcomes of late-onset dietary restriction in rodents. Ann N Y Acad Sci 1100:431–441PubMedCrossRefGoogle Scholar
  46. Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A (2007) An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol 17:1646–1656PubMedPubMedCentralCrossRefGoogle Scholar
  47. Guarente L, Picard F (2005) Calorie restriction–the SIR2 connection. Cell 120:473–482PubMedCrossRefGoogle Scholar
  48. Haigis MC, Guarente LP (2006) Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction. Genes Dev 20:2913–2921PubMedCrossRefGoogle Scholar
  49. Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 26:212–220PubMedCrossRefGoogle Scholar
  50. Halloran J, Hussong SA, Burbank R, Podlutskaya N, Fischer KE, Sloane LB, Austad SN, Strong R, Richardson A, Hart MJ, Galvan V (2012) Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience 223:102–113PubMedPubMedCentralCrossRefGoogle Scholar
  51. Hamadeh MJ, Rodriguez MC, Kaczor JJ, Tarnopolsky MA (2005) Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse. Muscle Nerve 31:214–220PubMedCrossRefGoogle Scholar
  52. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395PubMedPubMedCentralGoogle Scholar
  53. Heitman J, Movva NR, Hall MN (1991) Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253:905–909PubMedCrossRefGoogle Scholar
  54. Hine C, Mitchell JR (2015) Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway. Exp Gerontol 68:26–32PubMedCrossRefGoogle Scholar
  55. Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Trevino-Villarreal JH, Mejia P, Ozaki CK, Wang R, Gladyshev VN, Madeo F, Mair WB, Mitchell JR (2015) Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell 160:132–144PubMedCrossRefGoogle Scholar
  56. Holloszy JO, Fontana L (2007) Caloric restriction in humans. Exp Gerontol 42:709–712PubMedPubMedCentralCrossRefGoogle Scholar
  57. Horie NC, Serrao VT, Simon SS, Polo Gascon MR, Xavier Dos Santos A, Zambone MA, Bigio de Freitas MM, Cunha-Neto E, Marques EL, Halpern A, Edna de Melo M, Mancini MC, Cercato C (2016) Cognitive effects of intentional weight loss in elderly obese individuals with mild cognitive impairment. J Clin Endocrinol Metab 101:1104–1112PubMedCrossRefGoogle Scholar
  58. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196PubMedCrossRefGoogle Scholar
  59. Hsu CC, Wahlqvist ML, Lee MS, Tsai HN (2011) Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin. J Alzheimers Dis 24:485–493PubMedGoogle Scholar
  60. Hu J, Lin T, Gao Y, Xu J, Jiang C, Wang G, Bu G, Xu H, Chen H, Zhang YW (2015) The resveratrol trimer miyabenol C inhibits beta-secretase activity and beta-amyloid generation. PLoS One 10:e0115973PubMedPubMedCentralCrossRefGoogle Scholar
  61. Huang TC, Lu KT, Wo YY, Wu YJ, Yang YL (2011) Resveratrol protects rats from Abeta-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. PLoS One 6:e29102PubMedPubMedCentralCrossRefGoogle Scholar
  62. Hulbert AJ (2005) On the importance of fatty acid composition of membranes for aging. J Theor Biol 234:277–288PubMedCrossRefGoogle Scholar
  63. Imfeld P, Bodmer M, Jick SS, Meier CR (2012) Metformin, other antidiabetic drugs, and risk of Alzheimer’s disease: a population-based case-control study. J Am Geriatr Soc 60:916–921PubMedCrossRefGoogle Scholar
  64. Ingram DK, Weindruch R, Spangler EL, Freeman JR, Walford RL (1987) Dietary restriction benefits learning and motor performance of aged mice. J Gerontol 42:78–81PubMedCrossRefGoogle Scholar
  65. Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS, deCabo R (2006) Calorie restriction mimetics: an emerging research field. Aging Cell 5:97–108PubMedCrossRefGoogle Scholar
  66. Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–590PubMedCrossRefGoogle Scholar
  67. Jiang M, Wang J, Fu J, Du L, Jeong H, West T, Xiang L, Peng Q, Hou Z, Cai H, Seredenina T, Arbez N, Zhu S, Sommers K, Qian J, Zhang J, Mori S, Yang XW, Tamashiro KL, Aja S, Moran TH, Luthi-Carter R, Martin B, Maudsley S, Mattson MP, Cichewicz RH, Ross CA, Holtzman DM, Krainc D, Duan W (2012) Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nat Med 18:153–158CrossRefGoogle Scholar
  68. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493:338–345PubMedPubMedCentralCrossRefGoogle Scholar
  69. Joseph JA, Fisher DR, Cheng V, Rimando AM, Shukitt-Hale B (2008) Cellular and behavioral effects of stilbene resveratrol analogues: implications for reducing the deleterious effects of aging. J Agric Food Chem 56:10544–10551PubMedCrossRefGoogle Scholar
  70. Juhasz G, Erdi B, Sass M, Neufeld TP (2007) Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Dev 21:3061–3066PubMedPubMedCentralCrossRefGoogle Scholar
  71. Kadonaga JT (1998) Eukaryotic transcription: an interlaced network of transcription factors and chromatin-modifying machines. Cell 92:307–313PubMedCrossRefGoogle Scholar
  72. Kanaya T, Kyo S, Takakura M, Ito H, Namiki M, Inoue M (1998) hTERT is a critical determinant of telomerase activity in renal-cell carcinoma. Int J Cancer 78:539–543PubMedCrossRefGoogle Scholar
  73. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14:885–890PubMedPubMedCentralCrossRefGoogle Scholar
  74. Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE (2009) Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem Int 54:111–118PubMedCrossRefGoogle Scholar
  75. Kaur M, Sharma S, Kaur G (2008) Age-related impairments in neuronal plasticity markers and astrocytic GFAP and their reversal by late-onset short term dietary restriction. Biogerontology 9:441–454PubMedCrossRefGoogle Scholar
  76. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464PubMedCrossRefGoogle Scholar
  77. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH (2007) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J 26:3169–3179PubMedPubMedCentralCrossRefGoogle Scholar
  78. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942–946PubMedCrossRefGoogle Scholar
  79. Ladiwala AR, Lin JC, Bale SS, Marcelino-Cruz AM, Bhattacharya M, Dordick JS, Tessier PM (2010) Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Abeta into off-pathway conformers. J Biol Chem 285:24228–24237PubMedPubMedCentralCrossRefGoogle Scholar
  80. Lafay-Chebassier C, Perault-Pochat MC, Page G, Rioux Bilan A, Damjanac M, Pain S, Houeto JL, Gil R, Hugon J (2006) The immunosuppressant rapamycin exacerbates neurotoxicity of Abeta peptide. J Neurosci Res 84:1323–1334PubMedCrossRefGoogle Scholar
  81. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122PubMedCrossRefGoogle Scholar
  82. Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T (2002) Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21:2383–2396PubMedPubMedCentralCrossRefGoogle Scholar
  83. Law BK (2005) Rapamycin: an anti-cancer immunosuppressant? Crit Rev Oncol Hematol 56:47–60PubMedCrossRefGoogle Scholar
  84. Lee J, Duan W, Long JM, Ingram DK, Mattson MP (2000) Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci 15:99–108PubMedCrossRefGoogle Scholar
  85. Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367–1375PubMedCrossRefGoogle Scholar
  86. Lee CC, Kuo YM, Huang CC, Hsu KS (2009) Insulin rescues amyloid beta-induced impairment of hippocampal long-term potentiation. Neurobiol Aging 30:377–387PubMedCrossRefGoogle Scholar
  87. Leibiger IB, Berggren PO (2006) Sirt1: a metabolic master switch that modulates lifespan. Nat Med 12:34–36 discussion 36 PubMedCrossRefGoogle Scholar
  88. Li E, Beard C, Jaenisch R (1993) Role for DNA methylation in genomic imprinting. Nature 366:362–365PubMedCrossRefGoogle Scholar
  89. Li Y, Liu L, Tollefsbol TO (2010) Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J 24:1442–1453PubMedPubMedCentralCrossRefGoogle Scholar
  90. Li Y, Daniel M, Tollefsbol TO (2011) Epigenetic regulation of caloric restriction in aging. BMC Med 9:98PubMedPubMedCentralCrossRefGoogle Scholar
  91. Li XM, Zhou MT, Wang XM, Ji MH, Zhou ZQ, Yang JJ (2014) Resveratrol pretreatment attenuates the isoflurane-induced cognitive impairment through its anti-inflammation and -apoptosis actions in aged mice. J Mol Neurosci 52:286–293PubMedCrossRefGoogle Scholar
  92. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21:8370–8377PubMedGoogle Scholar
  93. Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289:2126–2128PubMedCrossRefGoogle Scholar
  94. Lin AL, Zheng W, Halloran JJ, Burbank RR, Hussong SA, Hart MJ, Javors M, Shih YY, Muir E, Solano Fonseca R, Strong R, Richardson AG, Lechleiter JD, Fox PT, Galvan V (2013) Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer’s disease. J Cereb Blood Flow Metab 33:1412–1421PubMedPubMedCentralCrossRefGoogle Scholar
  95. Lipinski MM, Zheng B, Lu T, Yan Z, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR, Yuan J (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci USA 107:14164–14169PubMedPubMedCentralCrossRefGoogle Scholar
  96. Lopez-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, Cascajo MV, Allard J, Ingram DK, Navas P, de Cabo R (2006) Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci USA 103:1768–1773PubMedPubMedCentralCrossRefGoogle Scholar
  97. Lord J, Cruchaga C (2014) The epigenetic landscape of Alzheimer’s disease. Nat Neurosci 17:1138–1140PubMedCrossRefGoogle Scholar
  98. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107:137–148PubMedCrossRefGoogle Scholar
  99. Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM (2009) Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci 29:9078–9089PubMedPubMedCentralCrossRefGoogle Scholar
  100. Mair W, Morantte I, Rodrigues AP, Manning G, Montminy M, Shaw RJ, Dillin A (2011) Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470:404–408PubMedPubMedCentralCrossRefGoogle Scholar
  101. Majumder S, Richardson A, Strong R, Oddo S (2011) Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. PLoS One 6:e25416PubMedPubMedCentralCrossRefGoogle Scholar
  102. Marambaud P, Zhao H, Davies P (2005) Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem 280:37377–37382PubMedCrossRefGoogle Scholar
  103. Marino G, Pietrocola F, Madeo F, Kroemer G (2014) Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers. Autophagy 10:1879–1882PubMedPubMedCentralCrossRefGoogle Scholar
  104. Martin B, Mattson MP, Maudsley S (2006) Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev 5:332–353PubMedPubMedCentralCrossRefGoogle Scholar
  105. Martin CK, Anton SD, Han H, York-Crowe E, Redman LM, Ravussin E, Williamson DA (2007) Examination of cognitive function during six months of calorie restriction: results of a randomized controlled trial. Rejuvenation Res 10:179–190PubMedPubMedCentralCrossRefGoogle Scholar
  106. Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, Schwab M, Pollak M, Zhang Y, Yu Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, de Cabo R (2013) Metformin improves healthspan and lifespan in mice. Nat Commun 4:2192PubMedPubMedCentralCrossRefGoogle Scholar
  107. Martins R, Lithgow GJ, Link W (2016) Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell 15:196–207PubMedCrossRefGoogle Scholar
  108. Marwarha G, Dasari B, Prabhakara JP, Schommer J, Ghribi O (2010) beta-Amyloid regulates leptin expression and tau phosphorylation through the mTORC1 signaling pathway. J Neurochem 115:373–384PubMedPubMedCentralCrossRefGoogle Scholar
  109. Masoro EJ (2005) Overview of caloric restriction and ageing. Mech Ageing Dev 126:913–922PubMedCrossRefGoogle Scholar
  110. Maswood N, Young J, Tilmont E, Zhang Z, Gash DM, Gerhardt GA, Grondin R, Roth GS, Mattison J, Lane MA, Carson RE, Cohen RM, Mouton PR, Quigley C, Mattson MP, Ingram DK (2004) Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson’s disease. Proc Natl Acad Sci USA 101:18171–18176PubMedPubMedCentralCrossRefGoogle Scholar
  111. Mattson MP (2002) Brain evolution and lifespan regulation: conservation of signal transduction pathways that regulate energy metabolism. Mech Ageing Dev 123:947–953PubMedCrossRefGoogle Scholar
  112. Mattson MP (2012) Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metab 16:706–722PubMedPubMedCentralCrossRefGoogle Scholar
  113. Mattson MP (2015) Lifelong brain health is a lifelong challenge: from evolutionary principles to empirical evidence. Ageing Res Rev 20:37–45PubMedCrossRefGoogle Scholar
  114. Mattson MP, Duan W, Guo Z (2003) Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms. J Neurochem 84:417–431PubMedCrossRefGoogle Scholar
  115. McCay CM, Crowell MF, Maynard LA (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5:155–171 discussion 172 PubMedGoogle Scholar
  116. Means LW, Higgins JL, Fernandez TJ (1993) Mid-life onset of dietary restriction extends life and prolongs cognitive functioning. Physiol Behav 54:503–508PubMedCrossRefGoogle Scholar
  117. Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, Caddle SD, Ziaugra L, Beijersbergen RL, Davidoff MJ, Liu Q, Bacchetti S, Haber DA, Weinberg RA (1997) hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90:785–795PubMedCrossRefGoogle Scholar
  118. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R (2011) Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 66:191–201PubMedCrossRefGoogle Scholar
  119. Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, Van Roekel S, Winkleman L, Strong R (2014) Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell 13:468–477PubMedPubMedCentralCrossRefGoogle Scholar
  120. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741PubMedCrossRefGoogle Scholar
  121. Mladenovic Djordjevic A, Perovic M, Tesic V, Tanic N, Rakic L, Ruzdijic S, Kanazir S (2010) Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. Neurochem Int 56:250–255PubMedCrossRefGoogle Scholar
  122. Mouton PR, Chachich ME, Quigley C, Spangler E, Ingram DK (2009) Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice. Neurosci Lett 464:184–187PubMedPubMedCentralCrossRefGoogle Scholar
  123. Munoz-Najar U, Sedivy JM (2011) Epigenetic control of aging. Antioxid Redox Signal 14:241–259PubMedPubMedCentralCrossRefGoogle Scholar
  124. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:277–283PubMedCrossRefGoogle Scholar
  125. Murphy T, Dias GP, Thuret S (2014) Effects of diet on brain plasticity in animal and human studies: mind the gap. Neural Plast 2014:563160PubMedPubMedCentralGoogle Scholar
  126. Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schroder S, Adler T, Afonso LC, Aguilar-Pimentel JA, Becker L, Garrett L, Hans W, Hettich MM, Holtmeier R, Holter SM, Moreth K, Prehn C, Puk O, Racz I, Rathkolb B, Rozman J, Naton B, Ordemann R, Adamski J, Beckers J, Bekeredjian R, Busch DH, Ehninger G, Graw J, Hofler H, Klingenspor M, Klopstock T, Ollert M, Stypmann J, Wolf E, Wurst W, Zimmer A, Fuchs H, Gailus-Durner V, Hrabe de Angelis M, Ehninger D (2013) Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest 123:3272–3291PubMedPubMedCentralCrossRefGoogle Scholar
  127. Nikolai S, Pallauf K, Huebbe P, Rimbach G (2015) Energy restriction and potential energy restriction mimetics. Nutr Res Rev 28:100–120PubMedCrossRefGoogle Scholar
  128. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cani O, Clementi E, Carruba MO, Valerio A (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317PubMedCrossRefGoogle Scholar
  129. Omodei D, Fontana L (2011) Calorie restriction and prevention of age-associated chronic disease. FEBS Lett 585:1537–1542PubMedPubMedCentralCrossRefGoogle Scholar
  130. Pamplona R, Barja G, Portero-Otin M (2002) Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation? Ann N Y Acad Sci 959:475–490PubMedCrossRefGoogle Scholar
  131. Pani G (2015) Neuroprotective effects of dietary restriction: evidence and mechanisms. Semin Cell Dev Biol 40:106–114PubMedCrossRefGoogle Scholar
  132. Park SK, Prolla TA (2005) Lessons learned from gene expression profile studies of aging and caloric restriction. Ageing Res Rev 4:55–65PubMedCrossRefGoogle Scholar
  133. Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH (2012) Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148:421–433PubMedPubMedCentralCrossRefGoogle Scholar
  134. Pasinetti GM, Eberstein JA (2008) Metabolic syndrome and the role of dietary lifestyles in Alzheimer’s disease. J Neurochem 106:1503–1514PubMedPubMedCentralCrossRefGoogle Scholar
  135. Patel NV, Gordon MN, Connor KE, Good RA, Engelman RW, Mason J, Morgan DG, Morgan TE, Finch CE (2005) Caloric restriction attenuates Abeta-deposition in Alzheimer transgenic models. Neurobiol Aging 26:995–1000PubMedCrossRefGoogle Scholar
  136. Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K (2011) Clinical trials of resveratrol. Ann N Y Acad Sci 1215:161–169PubMedCrossRefGoogle Scholar
  137. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157–168PubMedPubMedCentralCrossRefGoogle Scholar
  138. Peric A, Annaert W (2015) Early etiology of Alzheimer’s disease: tipping the balance toward autophagy or endosomal dysfunction? Acta Neuropathol 129:363–381PubMedPubMedCentralCrossRefGoogle Scholar
  139. Perrone CE, Malloy VL, Orentreich DS, Orentreich N (2013) Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents. Exp Gerontol 48:654–660PubMedCrossRefGoogle Scholar
  140. Porquet D, Casadesus G, Bayod S, Vicente A, Canudas AM, Vilaplana J, Pelegri C, Sanfeliu C, Camins A, Pallas M, del Valle J (2013) Dietary resveratrol prevents Alzheimer’s markers and increases life span in SAMP8. Age (Dordr) 35:1851–1865CrossRefGoogle Scholar
  141. Porquet D, Grinan-Ferre C, Ferrer I, Camins A, Sanfeliu C, Del Valle J, Pallas M (2014) Neuroprotective role of trans-resveratrol in a murine model of familial Alzheimer’s disease. J Alzheimers Dis 42:1209–1220PubMedGoogle Scholar
  142. Prolla TA (2002) DNA microarray analysis of the aging brain. Chem Senses 27:299–306PubMedCrossRefGoogle Scholar
  143. Pugh TD, Oberley TD, Weindruch R (1999) Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. Cancer Res 59:1642–1648PubMedGoogle Scholar
  144. Pyo JO, Yoo SM, Ahn HH, Nah J, Hong SH, Kam TI, Jung S, Jung YK (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4:2300PubMedPubMedCentralCrossRefGoogle Scholar
  145. Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB, Group CS (2015) A 2-Year Randomized Controlled Trial of Human Caloric Restriction: feasibility and Effects on Predictors of Health Span and Longevity. J Gerontol A Biol Sci Med Sci 70:1097–1104PubMedCrossRefGoogle Scholar
  146. Redman LM, Ravussin E (2011) Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes. Antioxid Redox Signal 14:275–287PubMedPubMedCentralCrossRefGoogle Scholar
  147. Reichardt LF (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 361:1545–1564PubMedPubMedCentralCrossRefGoogle Scholar
  148. Ribaric S (2012) Diet and aging. Oxid Med Cell Longev 2012:741468PubMedPubMedCentralCrossRefGoogle Scholar
  149. Richardson A, Galvan V, Lin AL, Oddo S (2015) How longevity research can lead to therapies for Alzheimer’s disease: the rapamycin story. Exp Gerontol 68:51–58PubMedCrossRefGoogle Scholar
  150. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434:113–118PubMedCrossRefGoogle Scholar
  151. Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998–16003PubMedPubMedCentralCrossRefGoogle Scholar
  152. Rothman SM, Griffioen KJ, Wan R, Mattson MP (2012) Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health. Ann N Y Acad Sci 1264:49–63PubMedPubMedCentralCrossRefGoogle Scholar
  153. Sanchez-Roman I, Barja G (2013) Regulation of longevity and oxidative stress by nutritional interventions: role of methionine restriction. Exp Gerontol 48:1030–1042PubMedCrossRefGoogle Scholar
  154. Santos J, Leitao-Correia F, Sousa MJ, Leao C (2015) Ammonium is a key determinant on the dietary restriction of yeast chronological aging in culture medium. Oncotarget 6:6511–6523PubMedCrossRefGoogle Scholar
  155. Savaskan E, Olivieri G, Meier F, Seifritz E, Wirz-Justice A, Muller-Spahn F (2003) Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity. Gerontology 49:380–383PubMedCrossRefGoogle Scholar
  156. Schafer MJ, Alldred MJ, Lee SH, Calhoun ME, Petkova E, Mathews PM, Ginsberg SD (2015) Reduction of beta-amyloid and gamma-secretase by calorie restriction in female Tg2576 mice. Neurobiol Aging 36:1293–1302PubMedCrossRefGoogle Scholar
  157. Schulingkamp RJ, Pagano TC, Hung D, Raffa RB (2000) Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev 24:855–872PubMedCrossRefGoogle Scholar
  158. Selkoe DJ (2011) Alzheimer’s disease. Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a004457 PubMedPubMedCentralGoogle Scholar
  159. Sharma S, Singh R, Kaur M, Kaur G (2010) Late-onset dietary restriction compensates for age-related increase in oxidative stress and alterations of HSP 70 and synapsin 1 protein levels in male Wistar rats. Biogerontology 11:197–209PubMedCrossRefGoogle Scholar
  160. Shen LR, Parnell LD, Ordovas JM, Lai CQ (2013) Curcumin and aging. BioFactors 39:133–140PubMedCrossRefGoogle Scholar
  161. Shytle RD, Tan J, Bickford PC, Rezai-Zadeh K, Hou L, Zeng J, Sanberg PR, Sanberg CD, Alberte RS, Fink RC, Roschek B Jr (2012) Optimized turmeric extract reduces beta-Amyloid and phosphorylated Tau protein burden in Alzheimer’s transgenic mice. Curr Alzheimer Res 9:500–506PubMedCrossRefGoogle Scholar
  162. Siman R, Cocca R, Dong Y (2015) The mTOR Inhibitor Rapamycin Mitigates Perforant Pathway Neurodegeneration and Synapse Loss in a Mouse Model of Early-Stage Alzheimer-Type Tauopathy. PLoS ONE 10:e0142340PubMedPubMedCentralCrossRefGoogle Scholar
  163. Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4:176–184PubMedCrossRefGoogle Scholar
  164. Smith DL Jr, Elam CF Jr, Mattison JA, Lane MA, Roth GS, Ingram DK, Allison DB (2010a) Metformin supplementation and life span in Fischer-344 rats. J Gerontol A Biol Sci Med Sci 65:468–474PubMedCrossRefGoogle Scholar
  165. Smith PJ, Blumenthal JA, Babyak MA, Craighead L, Welsh-Bohmer KA, Browndyke JN, Strauman TA, Sherwood A (2010b) Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension 55:1331–1338PubMedPubMedCentralCrossRefGoogle Scholar
  166. Sohal RS, Forster MJ (2014) Caloric restriction and the aging process: a critique. Free Radic Biol Med 73:366–382PubMedCrossRefGoogle Scholar
  167. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273:59–63PubMedPubMedCentralCrossRefGoogle Scholar
  168. Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H (1994) Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 74:121–133PubMedCrossRefGoogle Scholar
  169. Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, Richardson A, Strong R, Galvan V (2010) Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer’s disease. PLoS One 5:e9979PubMedPubMedCentralCrossRefGoogle Scholar
  170. Sridhar GR, Lakshmi G, Nagamani G (2015) Emerging links between type 2 diabetes and Alzheimer’s disease. World J Diabetes 6:744–751PubMedPubMedCentralCrossRefGoogle Scholar
  171. Srivastava S, Haigis MC (2011) Role of sirtuins and calorie restriction in neuroprotection: implications in Alzheimer’s and Parkinson’s diseases. Curr Pharm Des 17:3418–3433PubMedCrossRefGoogle Scholar
  172. Stenesen D, Suh JM, Seo J, Yu K, Lee KS, Kim JS, Min KJ, Graff JM (2013) Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies. Cell Metab 17:101–112PubMedPubMedCentralCrossRefGoogle Scholar
  173. Stewart J, Mitchell J, Kalant N (1989) The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes. Neurobiol Aging 10:669–675PubMedCrossRefGoogle Scholar
  174. Strong R, Miller RA, Astle CM, Baur JA, de Cabo R, Fernandez E, Guo W, Javors M, Kirkland JL, Nelson JF, Sinclair DA, Teter B, Williams D, Zaveri N, Nadon NL, Harrison DE (2013) Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 68:6–16PubMedCrossRefGoogle Scholar
  175. Subramanian L, Youssef S, Bhattacharya S, Kenealey J, Polans AS, van Ginkel PR (2010) Resveratrol: challenges in translation to the clinic–a critical discussion. Clin Cancer Res 16:5942–5948PubMedPubMedCentralCrossRefGoogle Scholar
  176. Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292:107–110PubMedCrossRefGoogle Scholar
  177. Theendakara V, Patent A, Peters Libeu CA, Philpot B, Flores S, Descamps O, Poksay KS, Zhang Q, Cailing G, Hart M, John V, Rao RV, Bredesen DE (2013) Neuroprotective Sirtuin ratio reversed by ApoE4. Proc Natl Acad Sci USA 110:18303–18308PubMedPubMedCentralCrossRefGoogle Scholar
  178. Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, Orosz L, Kovacs AL, Csikos G, Sass M, Vellai T (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4:330–338PubMedCrossRefGoogle Scholar
  179. Tung BT, Rodriguez-Bies E, Ballesteros-Simarro M, Motilva V, Navas P, Lopez-Lluch G (2014) Modulation of endogenous antioxidant activity by resveratrol and exercise in mouse liver is age dependent. J Gerontol A Biol Sci Med Sci 69:398–409PubMedCrossRefGoogle Scholar
  180. Tung BT, Rodriguez-Bies E, Thanh HN, Le-Thi-Thu H, Navas P, Sanchez VM, Lopez-Lluch G (2015) Organ and tissue-dependent effect of resveratrol and exercise on antioxidant defenses of old mice. Aging Clin Exp Res 27:775–783PubMedCrossRefGoogle Scholar
  181. Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, Reynolds BA, Brewer JB, Rissman RA, Raman R, Aisen PS, Alzheimer’s Disease Cooperative S (2015) A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology 85:1383–1391PubMedPubMedCentralCrossRefGoogle Scholar
  182. van der Heide LP, Ramakers GM, Smidt MP (2006) Insulin signaling in the central nervous system: learning to survive. Prog Neurobiol 79:205–221PubMedCrossRefGoogle Scholar
  183. Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA (2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107:149–159PubMedCrossRefGoogle Scholar
  184. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426:620PubMedCrossRefGoogle Scholar
  185. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F (2012) Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) 122:253–270CrossRefGoogle Scholar
  186. Vivar C, Potter MC, van Praag H (2013) All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis. Curr Top Behav Neurosci 15:189–210PubMedPubMedCentralCrossRefGoogle Scholar
  187. Wakeling LA, Ions LJ, Ford D (2009) Could Sirt1-mediated epigenetic effects contribute to the longevity response to dietary restriction and be mimicked by other dietary interventions? Age (Dordr) 31:327–341CrossRefGoogle Scholar
  188. Wang J, Ho L, Qin W, Rocher AB, Seror I, Humala N, Maniar K, Dolios G, Wang R, Hof PR, Pasinetti GM (2005) Caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer’s disease. FASEB J 19:659–661PubMedCrossRefGoogle Scholar
  189. Wang Y, Oh SW, Deplancke B, Luo J, Walhout AJ, Tissenbaum HA (2006) C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech Ageing Dev 127:741–747PubMedCrossRefGoogle Scholar
  190. Wang DT, He J, Wu M, Li SM, Gao Q, Zeng QP (2015) Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice. PeerJ 3:e822PubMedPubMedCentralCrossRefGoogle Scholar
  191. Weiss EP, Fontana L (2011) Caloric restriction: powerful protection for the aging heart and vasculature. Am J Physiol Heart Circ Physiol 301:H1205–H1219PubMedPubMedCentralCrossRefGoogle Scholar
  192. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK, Woodward MA, Miller RA (2012) Rapamycin slows aging in mice. Aging Cell 11:675–682PubMedPubMedCentralCrossRefGoogle Scholar
  193. Willcox BJ, Willcox DC (2014) Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: controversies and clinical implications. Curr Opin Clin Nutr Metab Care 17:51–58PubMedGoogle Scholar
  194. Witte AV, Fobker M, Gellner R, Knecht S, Floel A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci USA 106:1255–1260PubMedPubMedCentralCrossRefGoogle Scholar
  195. Witte AV, Kerti L, Margulies DS, Floel A (2014) Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J Neurosci 34:7862–7870PubMedCrossRefGoogle Scholar
  196. Wood SH, van Dam S, Craig T, Tacutu R, O’Toole A, Merry BJ, de Magalhaes JP (2015) Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging. Genome Biol 16:285PubMedPubMedCentralCrossRefGoogle Scholar
  197. Wu P, Shen Q, Dong S, Xu Z, Tsien JZ, Hu Y (2008) Calorie restriction ameliorates neurodegenerative phenotypes in forebrain-specific presenilin-1 and presenilin-2 double knockout mice. Neurobiol Aging 29:1502–1511PubMedCrossRefGoogle Scholar
  198. Wu JJ, Liu J, Chen EB, Wang JJ, Cao L, Narayan N, Fergusson MM, Rovira II, Allen M, Springer DA, Lago CU, Zhang S, DuBois W, Ward T, deCabo R, Gavrilova O, Mock B, Finkel T (2013) Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep 4:913–920PubMedPubMedCentralCrossRefGoogle Scholar
  199. Zhang S, Salemi J, Hou H, Zhu Y, Mori T, Giunta B, Obregon D, Tan J (2010) Rapamycin promotes beta-amyloid production via ADAM-10 inhibition. Biochem Biophys Res Commun 398:337–341PubMedPubMedCentralCrossRefGoogle Scholar
  200. Zhang Y, Bokov A, Gelfond J, Soto V, Ikeno Y, Hubbard G, Diaz V, Sloane L, Maslin K, Treaster S, Rendon S, van Remmen H, Ward W, Javors M, Richardson A, Austad SN, Fischer K (2014) Rapamycin extends life and health in C57BL/6 mice. J Gerontol A Biol Sci Med Sci 69:119–130PubMedCrossRefGoogle Scholar
  201. Zhao HF, Li N, Wang Q, Cheng XJ, Li XM, Liu TT (2015a) Resveratrol decreases the insoluble Abeta1-42 level in hippocampus and protects the integrity of the blood-brain barrier in AD rats. Neuroscience 310:641–649PubMedCrossRefGoogle Scholar
  202. Zhao J, Zhai B, Gygi SP, Goldberg AL (2015b) mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy. Proc Natl Acad Sci USA 112:15790–15797PubMedPubMedCentralCrossRefGoogle Scholar
  203. Zhao Z, Sui Y, Gao W, Cai B, Fan D (2015c) Effects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model. J Int Med Res 43:67–79PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Caroline Van Cauwenberghe
    • 1
    • 2
  • Charysse Vandendriessche
    • 1
    • 2
  • Claude Libert
    • 1
    • 2
  • Roosmarijn E. Vandenbroucke
    • 1
    • 2
  1. 1.Inflammation Research Center (IRC), Mouse Genetics in Inflammation (MGI)Ghent University, VIBGhentBelgium
  2. 2.Department of Biomedical Molecular BiologyGhent UniversityGhentBelgium

Personalised recommendations