Intermittent Fasting-Dietary Restriction as a Geroprotector

  • Gurcharan Kaur
  • Taranjeet Kaur
  • Anuradha Sharma
  • Shaffi Manchanda
  • Harpal Singh
  • Shikha Kalotra
  • Payal Bajaj


Old age is one of the major determinants of neurodegenerative diseases. There have been major advancements in understanding the biology of aging along with various interventions that may promote healthy aging. Many nutritional interventions such as caloric restriction, periodic fasting, and alternate day fasting have been proposed that may hamper age-associated cognitive decline. Among the various regimens, intermittent fasting-dietary restriction (IF-DR) seems to be most promising as it has been well documented to provide neuroprotection by enhancing synaptic plasticity and neurogenesis. It is also known to prolong life span and delay the onset of age-associated disorders by reducing inflammation and oxidative stress. IF-DR regimen is known to possibly work by establishing a conditioning response which maintains survival mode in organisms by focusing on energy conservation, thereby causing a metabolic shift from growth to maintenance activities and hence promoting anti-aging effects. IF-DR regimen is also known to improve many physiological indicators such as reduced levels of leptin, insulin, amount of body fat, reduced blood pressure, and increase in resistance to stress. Thus, IF-DR regimen initiated in middle or old age has the ability to impede age-associated neurodegeneration and cognitive decline and may be a potential intervention to abrogate age-related impairment of brain functions.


Aging Cognitive decline Intermittent fasting-dietary restriction Neuroprotection Oxidative stress 



Alzheimer’s disease


Alternate day caloric restriction


Alternate day fed


Ad libitum


Adenosine monophosphate


α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Adenosine monophosphate-activated protein kinase


Arcuate nucleus


Adenosine triphosphate


Brain-derived neurotrophic factor


Cornu ammonis








Caloric restriction


Cyclic AMP response element-binding protein


Deoxyribonucleic acid


Dietary restriction


Forkhead box O3




Glial fibrillary acidic protein


Glucagon-like peptide 1


Glutamate receptor subunit


Gonadotropin-releasing hormone






Hypothalamic-pituitary-adrenal axis


Ionized calcium-binding adapter molecule-1


Intracellular adhesion molecules


Intermittent fasting-dietary restriction


Intermittent fasting-dietary restriction plus herbal supplementation




Inducible nitric oxide synthase


Kainic acid




Middle-aged ad libitum fed


Mitogen-activated protein kinase


Middle-aged dietary restriction


1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (neurotoxin)


Messenger ribonucleic acid


Mammalian target of rapamycin


Nicotinamide adenine dinucleotide


Nicotinamide adenine dinucleotide plus hydrogen


Neural cell adhesion molecule


Nuclear factor kappa B




Nitric oxide


3-Nitropropionic acid




Nuclear respiratory factor


Neurotrophic factor-3


Piriform cortex


Parkinson’s disease


Proliferator-activated receptor gamma coactivator 1-alpha


Phosphatidylinositol 3-kinase


Plasma membrane


Plasma membrane redox system


Peroxisome proliferator-activated receptor gamma


Polysialylated neural cell adhesion molecule


Postsynaptic density protein 95 kDa


Reactive oxygen species




Suppressor of cytokine signaling 3


Thiobarbituric acid reactive substances


Mitochondrial transcription factor A


Tyrosine kinase


Vascular cell adhesion molecule


  1. Amigo I, Kowaltowski AJ (2014) Dietary restriction in cerebral bioenergetics and redox state. Redox Biol 2:296–304PubMedPubMedCentralCrossRefGoogle Scholar
  2. Anton S, Leeuwenburgh C (2013) Fasting or caloric restriction for healthy aging. Exp Gerontol 48:1003–1005PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bruce-Keller AJ, Umberger G, McFall R et al (1999) Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann Neurol 45:8–15PubMedCrossRefGoogle Scholar
  4. Caccamo A, Maldonado MA, Bokov AF et al (2010) CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 107:22687–22692PubMedPubMedCentralCrossRefGoogle Scholar
  5. Canto C, Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20(2):98PubMedPubMedCentralCrossRefGoogle Scholar
  6. Canto C, Auwerx J (2011) Calorie restriction: is AMPK a key sensor and effector? Physiology 26(4):214–224PubMedCrossRefGoogle Scholar
  7. Castello L, Froio T, Maina M et al (2010) Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation. Free Radic Biol Med 48:47–54PubMedCrossRefGoogle Scholar
  8. Catenacci VA, Pan Z, Ostendorf D et al (2016) A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity 24:1874–1883PubMedCrossRefGoogle Scholar
  9. Chung HY, Kim HJ, Kim KW et al (2002) Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction. Microsc Res Tech 59:264–272PubMedCrossRefGoogle Scholar
  10. Civitarese AE, Carling S, Heilbronn LK et al (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4(3):e76PubMedPubMedCentralCrossRefGoogle Scholar
  11. Cohen HY, Miller C, Bitterman KJ et al (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305(5682):390–392PubMedCrossRefGoogle Scholar
  12. Cotman CW, Berchtold NC, Christie LA (2007) Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30:464–472PubMedCrossRefGoogle Scholar
  13. Cui L, Jeong H, Borovecki F et al (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127:59–69PubMedCrossRefGoogle Scholar
  14. Dalle-Donne I, Rossi R, Giustarini D et al (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329(1):23–38PubMedPubMedCentralCrossRefGoogle Scholar
  15. Deogracias R, Espliguero G, Iglesias T et al (2004) Expression of the neurotrophin receptor trkB is regulated by the cAMP/CREB pathway in neurons. Mol Cell Neurosci 26(3):470–480PubMedCrossRefGoogle Scholar
  16. Donmez G, Arun A, Chung CY et al (2012) SIRT1 protects against α-synuclein aggregation by activating molecular chaperones. J Neurosci 32(1):124–132PubMedPubMedCentralCrossRefGoogle Scholar
  17. 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(2):195–206PubMedCrossRefGoogle Scholar
  18. Duan W, Guo Z, Mattson MP (2001) Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice. J Neurochem 76:619–626PubMedCrossRefGoogle Scholar
  19. Duan W, Guo Z, Jiang H et al (2003) Reversal of behavioral and metabolic abnormalities, and insulin resistance syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic factor. Endocrinology 144:2446–2453PubMedCrossRefGoogle Scholar
  20. Egan MF, Kojima M, Callicott JH et al (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112:257–269PubMedCrossRefGoogle Scholar
  21. Fann DYW, Ng GYQ, Poh L et al (2017) Positive effects of intermittent fasting in ischemic stroke. Exp Gerontol 89:93–102PubMedCrossRefGoogle Scholar
  22. Felies M, Von Hörsten S, Pabst R et al (2004) Neuropeptide Y stabilizes body temperature and prevents hypotension in endotoxaemic rats. J Physiol 561:245–252PubMedPubMedCentralCrossRefGoogle Scholar
  23. Fernandez-Fernandez R, Martini AC, Navarro VM et al (2006) Novel signals for the integration of energy balance and reproduction. Mol Cell Endocrinol 25:127–132CrossRefGoogle Scholar
  24. Finkbeiner S (2000) CREB couples neurotrophin signals to survival messages. Neuron 25:11–14PubMedCrossRefGoogle Scholar
  25. Fiskum G, Danilov CA, Mehrabian Z et al (2008) Post ischemic oxidative stress promotes mitochondrial metabolic failure in neurons and astrocytes. Ann N Y Acad Sci 1147:129–138PubMedPubMedCentralCrossRefGoogle Scholar
  26. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span–from yeast to humans. Science 328(5976):321–326PubMedPubMedCentralCrossRefGoogle Scholar
  27. Fusco S, Ripoli C, Podda MV et al (2012) A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction. Proc Natl Acad Sci U S A 109(2):621–626PubMedCrossRefGoogle Scholar
  28. Gao Z, Zhang J, Kheterpal I et al (2011) Sirtuin 1 (SIRT1) protein degradation in response to persistent c-Jun N-terminal kinase 1 (JNK1) activation contributes to hepatic steatosis in obesity. J Biol Chem 286(25):22227–22234PubMedPubMedCentralCrossRefGoogle Scholar
  29. Gehrmann J, Matsumoto Y, Kreutzberg GW (1995) Microglia: intrinsic immuneffector cell of the brain. Brain Res Rev 3:269–287CrossRefGoogle Scholar
  30. Govic A, Levay EA, Hazi A et al (2008) Alterations in male sexual behaviour, attractiveness and testosterone levels induced by an adult-onset calorie restriction regimen. Behav Brain Res 190:140–146PubMedCrossRefGoogle Scholar
  31. Greenberg ME, Xu B, Lu B et al (2009) New insights in the biology of BDNF synthesis and release: implications in CNS function. J Neurosci 29:12764–12767PubMedPubMedCentralCrossRefGoogle Scholar
  32. Grosjean J, Kiriakidis S, Reilly K et al (2006) Vascular endothelial growth factor signalling in endothelial cell survival: a role for NFκB. Biochem Biophys Res Commun 340:984–994PubMedCrossRefGoogle Scholar
  33. Gross DN, Van Den Heuvel APJ, Birnbaum MJ (2008) The role of FoxO in the regulation of metabolism. Oncogene 27(16):2320–2336PubMedCrossRefGoogle Scholar
  34. Guarente L (2000) Sir2 links chromatin silencing, metabolism, and aging. Genes Dev 14:1021–1026PubMedGoogle Scholar
  35. Hamilton ML, Van Remmen H, Drake JA et al (2001) Does oxidative damage to DNA increase with age? Proc Natl Acad Sci U S A 98:10469–10474PubMedPubMedCentralCrossRefGoogle Scholar
  36. Hariri AR, Goldberg TE, Mattay VS et al (2003) Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci 23:6690–6694PubMedCrossRefGoogle Scholar
  37. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300PubMedCrossRefGoogle Scholar
  38. Horne BD, Muhlestein JB, Anderson JL (2015) Health effects of intermittent fasting: hormesis or harm? A systematic review. Am J Clin Nutr 102:464–470PubMedCrossRefGoogle Scholar
  39. Hyun DH, Emerson SS, Jo DG et al (2006) Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging. Proc Natl Acad Sci U S A 103(52):19908–19912PubMedPubMedCentralCrossRefGoogle Scholar
  40. Ido Y, Duranton A, Lan F et al (2015) Resveratrol prevents oxidative stress-induced senescence and proliferative dysfunction by activating the AMPK-FOXO3 cascade in cultured primary human keratinocytes. PLoS One 10(2):e0115341PubMedPubMedCentralCrossRefGoogle Scholar
  41. Idrobo F, Nandy K, Mostofsky DI et al (1987) Dietary restriction: effects on radial maze learning and lipofuscin pigment deposition in the hippocampus and frontal cortex. Arch Gerontol Geriatr 6:355–362PubMedCrossRefGoogle Scholar
  42. Imai Y, Kohsaka S (2002) Intracellular signaling in M-CSF-induced microglia activation: role of Iba1. Glia 40:164–174PubMedCrossRefGoogle Scholar
  43. Johnson JB, Summer W, Cutler RG et al (2007) Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 42(5):665–674PubMedCrossRefGoogle Scholar
  44. Kauffman AL, Ashraf JM, Corces-Zimmerman MR et al (2010) Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age. PLoS Biol 8(5):e1000372PubMedPubMedCentralCrossRefGoogle Scholar
  45. Kaur G, Lakhman SS (2012) Dietary restriction as a potential intervention to retard age-associated impairment of brain functions. In: Thakur MK, Rattan SIS (eds) Brain aging and therapeutic interventions, 1st edn. Springer, Netherlands, pp 147–157CrossRefGoogle Scholar
  46. 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
  47. Kerr F, Augustin H, Piper MD et al (2011) Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer’s disease. Neurobiol Aging 32(11):1977–1989PubMedPubMedCentralCrossRefGoogle Scholar
  48. Komatsu T, Chiba T, Yamaza H et al (2008) Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8. Exp Gerontol 43:339–346PubMedCrossRefGoogle Scholar
  49. Koubova J, Guarente L (2003) How does calorie restriction work? Genes Dev 17:313–321PubMedCrossRefGoogle Scholar
  50. Kuipers SD, Bramham CR (2006) Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr Opin Drug Discov Devel 9:580–586PubMedGoogle Scholar
  51. Kumar S, Kaur G (2013) Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis. PLoS One 8:e52416PubMedPubMedCentralCrossRefGoogle Scholar
  52. Kumar S, Parkash J, Kataria H et al (2009) Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain. Neurosci Res 65:367–374PubMedCrossRefGoogle Scholar
  53. Kume S, Uzu T, Horiike K et al (2010) Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 120(4):1043–1055PubMedPubMedCentralCrossRefGoogle Scholar
  54. Lara-Padilla E, Godínez-Victoria M, Drago-Serrano ME et al (2015) Intermittent fasting modulates IgA levels in the small intestine under intense stress: a mouse model. J Neuroimmunol 285:22–30PubMedCrossRefGoogle Scholar
  55. Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhance-ment of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367–1375PubMedCrossRefGoogle Scholar
  56. Levay EA, Tammer AH, Penman J et al (2010) Calorie restriction at increasing levels leads to augmented concentrations of corticosterone and decreasing concentrations of testosterone in rats. Nutr Res 30:366–373PubMedCrossRefGoogle Scholar
  57. Li L, Wang Z, Zuo Z (2013) Chronic intermittent fasting improves cognitive functions and brain structures in mice. PLoS One 8:e66069PubMedPubMedCentralCrossRefGoogle Scholar
  58. Liu HX, Zhang JJ, Zhen P et al (2005) Altered expression of MAP-2, GAP-43 and synaptophysin in the hippocampus of rats with chronic cerebral hypoperfusion correlates with cognitive impairment. Mol Brain Res 139:169–177PubMedCrossRefGoogle Scholar
  59. Loeb LA, Wallace DC, Martin GM (2005) The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. Proc Natl Acad Sci U S A 102(52):18769–18770PubMedPubMedCentralCrossRefGoogle Scholar
  60. Longo VD, Mattson MP (2014) Fasting: molecular mechanisms and clinical applications. Cell Metab 19:181–192PubMedPubMedCentralCrossRefGoogle Scholar
  61. Lopez-Lluch G, Hunt N, Jones B et al (2006) Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci U S A 103(6):1768–1773PubMedPubMedCentralCrossRefGoogle Scholar
  62. López-Otín C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217PubMedPubMedCentralCrossRefGoogle Scholar
  63. Lu Y, Christian K, Lu B (2008) BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 89:312–323PubMedCrossRefGoogle Scholar
  64. Luheshi GN, Gardner JD, Rushforth DA et al (1999) Leptin actions on food intake and body temperature are mediated by IL-1. Proc Natl Acad Sci U S A 96:7047–7052PubMedPubMedCentralCrossRefGoogle Scholar
  65. MacDonald L, Radler M, Paolini AG et al (2011) Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias. Am J Physiol Regul Integr Comp Physiol 301:R172–R184PubMedCrossRefGoogle Scholar
  66. MacDonald L, Hazi A, Paolini AG et al (2014) Calorie restriction dose-dependently abates lipopolysaccharide-induced fever, sickness behavior, and circulating interleukin-6 while increasing corticosterone. Brain Behav Immun 40:18–26PubMedCrossRefGoogle Scholar
  67. Mattson MP (2009) Mitochondria in Neuroplasticity, Neurologic Disease and Aging. Blood 114:SCI-2Google Scholar
  68. Marosi K, Mattson MP (2014) BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab 25:89–98PubMedCrossRefGoogle Scholar
  69. Martin B, Mattson MP, Maudsley S (2006) Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev 5(3):332–353PubMedPubMedCentralCrossRefGoogle Scholar
  70. Mattson MP (2003) Gene–diet interactions in brain aging and neurodegenerative disorders. Ann Intern Med 139:441–444PubMedCrossRefGoogle Scholar
  71. Mattson MP (2008) Hormesis defined. Ageing Res Rev 7:1–7PubMedCrossRefGoogle Scholar
  72. Mattson MP (2015) Lifelong brain health is a lifelong challenge: from evolutionary principles to empirical evidence. Ageing Res Rev 20:37–45PubMedCrossRefGoogle Scholar
  73. Mattson MP, Duan W, Pedersen WA et al (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6(1–2):69–81PubMedCrossRefGoogle Scholar
  74. 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
  75. Mattson MP, Longo VD, Harvie M (2017) Impact of intermittent fasting on health and disease processes. Ageing Res Rev 39:46–58PubMedCrossRefGoogle Scholar
  76. Morselli E, Maiuri MC, Markaki M et al (2010) Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis 1(1):e10PubMedPubMedCentralCrossRefGoogle Scholar
  77. Munch G, Lüth HJ, Wong A et al (2000) Crosslinking of α-synuclein by advanced glycation endproducts—an early pathophysiological step in Lewy body formation? J Chem Neuroanat 20(3):253–257PubMedCrossRefGoogle Scholar
  78. Nakashima K, Yakabe Y (2007) AMPK activation stimulates myofibrillar protein degradation and expression of atrophy-related ubiquitin ligases by increasing FOXO transcription factors in C2C12 myotubes. Biosci Biotechnol Biochem 71(7):1650–1656CrossRefGoogle Scholar
  79. Nemoto S, Fergusson MM, Finkel T (2005) SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1α. J Biol Chem 280:16456–16460PubMedCrossRefGoogle Scholar
  80. Ntsapi C, Loos B (2016) Caloric restriction and the precision-control of autophagy: a strategy for delaying neurodegenerative disease progression. Exp Gerontol 83:97–111PubMedCrossRefGoogle Scholar
  81. Pani G (2015) Neuroprotective effects of dietary restriction: evidence and mechanisms. Semin Cell Dev Biol 40:106–114PubMedCrossRefGoogle Scholar
  82. Park H, Poo MM (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14:7–23PubMedCrossRefGoogle Scholar
  83. Parker JA, Arango M, Abderrahmane S et al (2005) Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 37(4):349–350PubMedCrossRefGoogle Scholar
  84. Powell JD, Pollizzi KN, Heikamp EB et al (2012) Regulation of immune responses by mTOR. Annu Rev Immunol 30:39–68PubMedCrossRefGoogle Scholar
  85. Price NL, Gomes AP, Ling AJ et al (2012) SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15(5):675–690PubMedPubMedCentralCrossRefGoogle Scholar
  86. Prolla TA, Mattson MP (2001) Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends Neurosci 24:21–31CrossRefGoogle Scholar
  87. Qiu G, Spangler EL, Wan R, Miller M, Mattson MP, So K, de Cabo R, Zou S, Ingram DK (2012) Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids. Neurobiol Aging 33(10):2398–2410PubMedCrossRefGoogle Scholar
  88. Radler ME, Hale MW, Kent S (2014) Calorie restriction attenuates lipopolysaccharide (LPS)-induced microglial activation in discrete regions of the hypothalamus and the subfornical organ. Brain Behav Immun 38:13–24PubMedCrossRefGoogle Scholar
  89. Radler ME, Wright BJ, Walker FR et al (2015) Calorie restriction increases lipopolysaccharide-induced neuropeptide Y immunolabeling and reduces microglial cell area in the arcuate hypothalamic nucleus. Neuroscience 285:236–247PubMedCrossRefGoogle Scholar
  90. Rattan SIS (2017) Hormetins as drugs for healthy aging. In: Vaiserman AM (ed) Anti-aging drugs: from basic research to clinical practice, 1st edn. Royal Society of Chemistry, London, pp 170–180CrossRefGoogle Scholar
  91. Riccio A, Ahn S, Davenport CM et al (1999) Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science 286:2358–2361PubMedCrossRefGoogle Scholar
  92. Robinet C, Pellerin L (2011) Brain-derived neurotrophic factor enhances the hippocampal expression of key postsynaptic proteins in vivo including the monocarboxylate transporter MCT2. Neuroscience 192:155–163PubMedCrossRefGoogle Scholar
  93. Rodgers JT, Lerin C, Haas W et al (2005) Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature 434:113–118PubMedCrossRefGoogle Scholar
  94. Sarkar D, Fisher PB (2006) Molecular mechanisms of aging-associated inflammation. Cancer Lett 236:13–23PubMedCrossRefGoogle Scholar
  95. Schulz TJ, Zarse K, Voigt A et al (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6(4):280–293PubMedCrossRefGoogle Scholar
  96. Serrano F, Klann E (2004) Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3:431–443PubMedCrossRefGoogle Scholar
  97. Sharma S, Kaur G (2008) Dietary restriction enhances kainate-induced increase in NCAM while blocking the glial activation in adult rat brain. Neurochem Res 33:1178–1188PubMedCrossRefGoogle Scholar
  98. Shi Y, Felley-Bosco E, Marti TM et al (2012) Starvation-induced activation of ATM/Chk2/p53 signaling sensitizes cancer cells to cisplatin. BMC Cancer 12:571PubMedPubMedCentralCrossRefGoogle Scholar
  99. Singh R, Lakhanpal D, Kumar S et al (2012) Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats. Age 34:917–933PubMedCrossRefGoogle Scholar
  100. Singh R, Manchanda S, Kaur T et al (2015) Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats. Biogerontology 16:775–788PubMedCrossRefGoogle Scholar
  101. Singh H, Kaur T, Manchanda S et al (2017) Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways. Biogerontology 18(4):601–614PubMedCrossRefGoogle Scholar
  102. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273(5271):59–63PubMedPubMedCentralCrossRefGoogle Scholar
  103. Solana R, Pawelec G, Tarazona R (2006) Aging and innate immunity. Immunity 24:491–494PubMedCrossRefGoogle Scholar
  104. Sonti G, Ilyin SE, Plata-Salamán CR (1996) Neuropeptide Y blocks and reverses interleukin-1β-induced anorexia in rats. Peptides 17:517–520PubMedCrossRefGoogle Scholar
  105. Sousa-Ferreira L, Garrido M, Nascimento-Ferreira I et al (2011) Moderate long-term modulation of neuropeptide Y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats. PLoS One 6:e22333PubMedPubMedCentralCrossRefGoogle Scholar
  106. Stanfel MN, Shamieh LS, Kaeberlein M et al (2009) The TOR pathway comes of age. Biochim Biophys Acta 1790(10):1067–1074PubMedPubMedCentralCrossRefGoogle Scholar
  107. St-Pierre J, Lin J, Krauss S et al (2003) Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1α and 1β (PGC-1α and PGC-1β) in muscle cells. J Biol Chem 278:26597–26603PubMedCrossRefGoogle Scholar
  108. Stranahan AM, Lee K, Martin B et al (2009) Voluntary exercise and caloric restriction enhance hippocampal den-dritic spine density and BDNF levels in diabetic mice. Hippocampus 19:951–961PubMedPubMedCentralCrossRefGoogle Scholar
  109. Su J, Liu J, Yan XY et al (2017) Cytoprotective effect of the UCP2-SIRT3 signaling pathway by decreasing mitochondrial oxidative stress on cerebral ischemia–reperfusion injury. Int J Mol Sci 18(7):E1599PubMedCrossRefGoogle Scholar
  110. Tang X, Chen XF, Chen HZ et al (2017) Mitochondrial Sirtuins in cardiometabolic diseases. Clin Sci 131(16):2063–2078PubMedCrossRefGoogle Scholar
  111. Tanner KG, Landry J, Sternglanz R et al (2000) Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci U S A 97:14178–14182PubMedPubMedCentralCrossRefGoogle Scholar
  112. Tinsley GM, La Bounty PM (2015) Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev 73:661–674PubMedCrossRefGoogle Scholar
  113. Valassi E, Scacchi M, Cavagnini F (2008) Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis 18:158–168PubMedCrossRefGoogle Scholar
  114. Varady KA (2011) Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? Obes Rev 12:e593–e601PubMedCrossRefGoogle Scholar
  115. Vasconcelos AR, Kinoshita PF, Yshii LM et al (2015) Effects of intermittent fasting on age-related changes on Na, K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus. Neurobiol Aging 36:1914–1923PubMedCrossRefGoogle Scholar
  116. Vasconcelos AR, Cabral-Costa JV, Mazucanti CH et al (2016) The role of steroid hormones in the modulation of neuroinflammation by dietary interventions. Front Endocrinol (Lausanne) 7(9)Google Scholar
  117. Walsh ME, Shi Y, Van Remmen H (2014) The effects of dietary restriction on oxidative stress in rodents. Free Radic Biol Med 66:88–99PubMedCrossRefGoogle Scholar
  118. Wohlgemuth SE, Seo AY, Marzetti E et al (2010) Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol 45(2):138–148CrossRefGoogle Scholar
  119. Wrann CD, White JP, Salogiannnis J et al (2013) Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab 18:649–659PubMedPubMedCentralCrossRefGoogle Scholar
  120. Wu Z, Puigserver P, Andersson U et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124CrossRefGoogle Scholar
  121. Xu J, Ji J, Yan XH (2012) Cross-talk between AMPK and mTOR in regulating energy balance. Crit Rev Food Sci Nutr 52(5):373–381PubMedCrossRefGoogle Scholar
  122. Yang F, Chu X, Yin M et al (2014) mTOR and autophagy in normal brain aging and caloric restriction ameliorating age-related cognition deficits. Behav Brain Res 264:82–90PubMedCrossRefGoogle Scholar
  123. Yu ZF, Mattson MP (1999) Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism. J Neurosci Res 57(6):830–839PubMedCrossRefGoogle Scholar
  124. Zhu H, Guo Q, Mattson MP (1999) Dietary restriction protects hippocampal neurons against the death-promoting action of a presenilin-1 mutation. Brain Res 842(1):224–229PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Gurcharan Kaur
    • 1
  • Taranjeet Kaur
    • 1
  • Anuradha Sharma
    • 1
  • Shaffi Manchanda
    • 1
  • Harpal Singh
    • 1
  • Shikha Kalotra
    • 1
  • Payal Bajaj
    • 1
  1. 1.Department of BiotechnologyGuru Nanak Dev UniversityAmritsarIndia

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