Skip to main content
SpringerLink
Log in

Will Calorie Restriction Stave Off Age-Related Brain Dysfunction, Specifically to Learning and Memory? A Review and Critique of the Rodent Literature

  • Chapter
  • First Online:
Calorie Restriction, Aging and Longevity

Abstract

While studies of long-term calorie restriction (CR) have pointed to a plethora of health benefits in numerous species including humans, the effects on the brain and brain function are less well known and understood. In this chapter the effect of long-term CR on learning and memory in aging populations of laboratory rats and mice is evaluated. Included in this chapter is a discussion of the methodological issues that investigators must consider in constructing studies designed to assess learning and memory in aged rodents as well as how these studies need to be designed to assess the effects of CR on learning and memory in these aged populations. A section on CR and brain aging is included to provide a more comprehensive background to the understanding of the effects of CR on learning and memory. As the reader will discern, the hypothesis that CR is beneficial to learning and memory in senescent animals is only partially supported by the current data.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams, M. M., Shi, L., Linville, M. C., Forbes, M. E., Long, A. B., Bennett, C., Newton, I. G., Carter, C. S., Sonntag, W. E., Riddle, D. R. and Brunso-Bechtold, J. K., 2008. Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability. Exp Neurol 211, 141–149.

    Article  PubMed  CAS  Google Scholar 

  • Arbel, I., Kadar, T., Silbermann, M. and Levy, A., 1994. The effects of long-term corticosterone administration on hippocampal morphology and cognitive performance of middle-aged rats. Brain Res 657, 227–235.

    Article  PubMed  CAS  Google Scholar 

  • Beatty, W. W., Clouse, B. A. and Bierley, R. A., 1987. Effects of long-term restricted feeding on radial arm maze performance by aged rats. Neurobiol Aging 8, 325–327.

    Article  PubMed  CAS  Google Scholar 

  • Bellush, L. L., Wright, A. M., Walker, J. P., Kopchik, J. and Colvin, R. A., 1996. Caloric restriction and spatial learning in old mice. Physiol Behav 60, 541–547.

    Article  PubMed  CAS  Google Scholar 

  • Bond, N. W., Everitt, A. V. and Walton, J., 1989. Effects of dietary restriction on radial arm maze performance and flavor memory in aged rats. Neurobiol Aging 10, 27–30.

    Article  PubMed  CAS  Google Scholar 

  • Carter, C. S., Leeuwenburgh, C., Daniels, M. and Foster, T. C., 2009. Influence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity. J Gerontol A Biol Sci Med Sci 64, 1–10.

    Google Scholar 

  • Contestabile, A., 2009. Benefits of caloric restriction on brain aging and related pathological states: understanding mechanisms to devise novel therapies. Curr Med Chem 16, 350–361.

    Article  PubMed  CAS  Google Scholar 

  • Dubey, A., Forster, M. J., Lal, H., Sohal, R. S., 1996. Effect of age and caloric intake on protein oxidation in different brain regions and on behavioral functions of the mouse. Arch Biochem Biophys 333, 189–197.

    Google Scholar 

  • Eckles-Smith, K., Clayton, D., Bickford, P., Browning, M. D., 2000. Caloric restriction prevents age-related deficits in LTP and in NMDA receptor expression. Brain Res Mol Brain Res 78, 154–162.

    Google Scholar 

  • Fitting, S., Booze, R. M., Gilbert, C. A. and Mactutus, C. F., 2008. Effects of chronic adult dietary restriction on spatial learning in the aged F344 × BN hybrid F1 rat. Physiol Behav 93, 560–569.

    Article  PubMed  CAS  Google Scholar 

  • Fontán-Lozano, A., Lopez-Lluch, G., Delgado-Garcia, J. M., Navas, P. and Carrion, A. M., 2008. Molecular bases of caloric restriction regulation of neuronal synaptic plasticity. Mol Neurobiol 38, 167–177.

    Article  PubMed  Google Scholar 

  • Fontán-Lozano, A., Sáez-Cassanelli, J. L., Inda, M. C., de los Santos-Arteaga, M., Sierra-Domínguez, S. A., López-Lluch, G., Delgado-García, J. M. and Carrión, A. M., 2007. Caloric restriction increases learning consolidation and facilitates synaptic plasticity through mechanisms dependent on NR2B subunits of the NMDA receptor. J Neurosci 27, 10185–10195.

    Article  PubMed  Google Scholar 

  • Freemantle, E., Vandal, M., Tremblay-Mercier, J., Tremblay, S., Blachere, J. C., Begin, M. E., Brenna, J. T., Windust, A. and Cunnane, S. C., 2006. Omega-3 fatty acids, energy substrates, and brain function during aging. Prostaglandins Leu- kot Essent Fatty Acids 75, 213–220.

    Article  CAS  Google Scholar 

  • Frick, K. and Fernandez, S. M., 2003. Enrichment enhances spatial memory and increases synaptophysin levels in aged female mice. Neurobiol Aging 24, 615–626.

    Article  PubMed  CAS  Google Scholar 

  • Gillet-Guyonnet, S. and Vellas, B., 2008. Caloric restriction and brain function. Curr Opinion Clin Nutr Metab Care 11, 686–692.

    Article  Google Scholar 

  • Goodrick, C. L., 1984. Effects of lifelong restricted feeding on complex maze performance in rats. Age 7, 1–2.

    Article  Google Scholar 

  • Gould, T. J., Bowenkamp, K. E., Larson, G., Zahniser, N. R. and Bickford, P. C., 1995. Effects of dietary restriction on motor learning and cerebellar noradrenergic dysfunction in aged F344 rats. Brain Res 684, 150–158.

    Article  PubMed  CAS  Google Scholar 

  • Guo, Z. and Mattson, M. P., 2000. Neurotrophic factors protect synaptic terminals against amyloid – and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function. Cerebral Cort 10, 173–179.

    Google Scholar 

  • Halagappa, A., Guo, Z., Pearson, M., Matuoka, Y., Cutler, R. G., LaFerla, F. M. and Mattson, M. P., 2007. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzeheimer’s disease. Neurobiol Disease 26, 212–220.

    Article  CAS  Google Scholar 

  • Hashimoto, T. and Watanabe, S., 2005. Chronic food deprivation enhances memory in mice-analysis with matched drive levels. Neurorep 16, 1129–1133.

    Article  Google Scholar 

  • Ingram, D. K., 1985. Analysis of age-related impairments in learning and memory in rodent models. Ann N Y Acad Sci 444, 312–331.

    Google Scholar 

  • Ingram, D. K., Jucker, M. and Spangler, E. L., 1994. Behavioral manifestations of aging. In Mohr U., Cungworth D. L., Capen C. C. (eds), Pathology of the Aging Rat, vol 2. ILSI Press, Washington, DC.

    Google Scholar 

  • Ingram, D. K., Weindruch, R., Spangler, E. L., Freeman, J. R. and Walford, R. L., 1987. Dietary restriction benefits learning and motor performance of aged mice. J Gerontol 42, 78–81.

    Article  PubMed  CAS  Google Scholar 

  • Joseph, J. A., Shukitt-Hale, B., Casadesus, G. and Fisher, D., 2005. Oxidative stress and inflammation in brain aging: nutritional considerations. Neurochem Res 30, 927–935.

    Article  PubMed  CAS  Google Scholar 

  • Lee, J., Duan, W., Long, J. M., Ingram, D. K. and Mattson, M. P., 2001. Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Molec Neurosci 15, 99–108.

    Article  Google Scholar 

  • Lindner, M. D., 1997. Reliability, distribution, and validity of age-related cognitive deficits in the Morris water maze. Neurbiol Learning Mem 68, 203–220.

    Article  CAS  Google Scholar 

  • Maei, H., Zaslavsky, K., Teixeira, C. M. and Frankland, P. W., 2009. What is the most sensitive measure of water maze probe test performance. Front Integr Neurosci 3, 1–9.

    Google Scholar 

  • Magistretti, P. J., Pellerin, L. and Martin, J. L., 2000. Brain energy metabolism: an integrated cellular perspective. In Bloom, F. E., Kupfer, D. J. (eds), Back to Psychopharmacology–The Fourth Generation of Progress. Raven, New York.

    Google Scholar 

  • Magnusson, K. R., 1997. Influence of dietary restriction on ionotropic glutamate receptors during aging in C57Bl mice. Mech Aging Dev 95, 187–202.

    Article  PubMed  CAS  Google Scholar 

  • Magnusson, K. R., 1998. The aging of the NMDA receptor complex. Frontiers Biosci 3, e70–e80.

    CAS  Google Scholar 

  • Magnusson, K. R., 2001. Influence of diet restriction on NMDA receptor subunits and learning during aging. Neuobiol Aging 22, 613–627.

    Article  CAS  Google Scholar 

  • Markowska, A. L., 1999. Life-long diet restriction failed to retard cognitive aging in Fischer-344 rats. Neuobiol Aging 20, 177–189.

    Article  CAS  Google Scholar 

  • Markowska, A. L. and Savonenko, A., 2002. Retardation of cognitive aging by life-long diet restriction: implications for genetic variance. Neurobiol Aging 23, 75–86.

    Article  PubMed  Google Scholar 

  • Martin, B., Pearson, M., Kebejian, L., Golden, E., Keselman, A., Bender, M., Carlson, O., Egan, J., Ladenheim, B., Cadet, J. L., Becker, K. G., Wood, W., Duffy, K., Vinayakumar, P., Maudsley, S. and Mattson, M., 2007. Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess. Endocrinology 148, 4318–4333.

    Article  PubMed  CAS  Google Scholar 

  • Masoro, E. J., 1993. Dietary restriction and aging. J Amer Geriat Soc 41, 994–999.

    PubMed  CAS  Google Scholar 

  • Mattison, J. A., Black, A., Huck, J., Moscrip, T., Handy, A., Tilmont, E., Roth, G. S., Lane, M. A. and Ingram, D. K., 2005. Age-related decline in caloric intake and motivation for food in rhesus monkeys. Neurobiol Aging 26, 1117–1127.

    Article  PubMed  Google Scholar 

  • Mattison, J., Wright, C., Bronson, R. T., Roth, G. S., Ingram, D. K. and Bartke, A., 2000. Studies of aging in Ames dwarf mice: effects of calorie restriction. J Am Aging Assoc 23, 9–16.

    Google Scholar 

  • Mattson, M. P., 2000. Neuroprotective signaling and the aging brain: take away my food and let me run. Brain Res 886, 47–53.

    Article  PubMed  CAS  Google Scholar 

  • Mattson, M. P. and Cheng, A., 2006. Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses. TINS 29, 632–639.

    PubMed  CAS  Google Scholar 

  • Mattson, M. P., Duan, W., Lee, J. and Guo, Z., 2001. Suppression of brain aging and neurodegenerative disorders by dietary restriction and environmental enrichment: molecular mechanisms. Mech Ageing Dev 122, 757–778.

    Article  PubMed  CAS  Google Scholar 

  • Mattson, M. P. and Lee, J., 2002. Increasing brain healthspan by dietary restriction. In Mattson, M. P. (ed), Diet-Brain Connections: Impact on Memory, Mood, Aging and Disease. Kluwer Academic, Norwell, MA.

    Chapter  Google Scholar 

  • May, P., Telford, N., Salo, D., Anderson, D., Kohama, S. G., Finch, C., Walford, R. L. and Weindruch, R., 1992. Failure of dietary restriction to retard age-related neurochemical changes in mice. Neurobiol Aging 13, 787–791.

    Article  PubMed  CAS  Google Scholar 

  • McCay, C., Crowell, M. and Maynard, L., 1935. The effect of retarded growth upon the length of life and upon ultimate size. J Nutr 10, 63–79.

    CAS  Google Scholar 

  • Means, L. W., Higgins, J. L. and Fernandez, T. J., 1993. Mid-life onset of dietary restriction extends life and prolongs cognitive functioning. Physiol Behav 54, 503–508.

    Article  PubMed  CAS  Google Scholar 

  • Minor, R. K., Chang, J. W. and de Cabo, R., 2009. Hungry for life: How the arcuate nucleus and neuropeptide Y may play a critical role in mediating the benefits of calorie restriction. Mol Cell Endocrinol 299, 79–88.

    Google Scholar 

  • Moroi-Fetters, S. E., Mervis, R. F., London, E. D. and Ingram, D. K., 1989. Dietary restriction suppresses age-related changes in dendritic spines. Neurobiol Aging 10, 317–322.

    Article  PubMed  CAS  Google Scholar 

  • Mouton, P. R., Chachich, M. E., Quigley, C., Spangler, E. and Ingram, D. K., 2009. Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice. Neurosci Lett 464, 184–187.

    Google Scholar 

  • Newton, I. G., Forbes, M. E., Legault, C., Johnson, J. E., Brunso-Bechtold, J. K. and Riddle, D. R., 2005. Caloric restriction does not reverse aging-related changes in hippocampal BDNF. Neurobiol Aging 26, 683–688.

    Google Scholar 

  • Patel, N. V. and Finch, C. E., 2002. The glucocorticoid paradox of caloric restriction in slowing brain aging. Neurobiol Aging 23, 707–717.

    Article  PubMed  CAS  Google Scholar 

  • Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinsky, N., Swindell, W. R., Kamara, D., Minor, R. K., Perez, E., Jamieson, H. A., Zhang, Y., Dunn, S. R., Sharma, K., Pleshko, N., Woollet, L. A., Csiszar, A., Ikeno, Y., Le Couteur, D., Elliott, P. J., Becker, K. G., Navas, P., Ingram, D. K., Wolf, N. S., Ungvari, Z., Sinclair, D. A. and de Cabo, R., 2008. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8, 157–168.

    Article  PubMed  CAS  Google Scholar 

  • Pitsikas, N. and Algeri, S., 1992. Deterioration of spatial and non-spatial reference and working memory in aged rats: protective effect of life-long calorie restriction. Neurobiol Aging 13, 369–373.

    Article  PubMed  CAS  Google Scholar 

  • Pitsikas, N., Carli, M., Fidecka, S. and Algeri, S., 1990. Effect of life-long hypocaloric diet on age-related changes in motor and cognitive behavior in a rat population. Neurobiol Aging 11, 417–423.

    Article  PubMed  CAS  Google Scholar 

  • Poon, H. F., Shepherd, H. M., Reed, T. T., Calabrese, V., Stella, A. M., Pennisi, G., Cai, J., Pierce, W. M., Klein, J. B. and Butterfield, D. A., 2006. Proteomics analysis provides insight into caloric restriction mediated oxidation and expression of brain proteins associated with age-related impaired cellular processes: mitochondrial dysfunction, glutamate dysregulation, and impaired protein synthesis. Neurobiol Aging 27, 1020–1034.

    Article  PubMed  CAS  Google Scholar 

  • Prolla, T. A. and Mattson, M. P., 2001. Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. TINS 11, S21–S31.

    Google Scholar 

  • Rotta, L. N., Schmidt, A. P., Mello e Souza, T., Nogueira, C. W., Souza, K. B., Izquierdo, I. A., Perry, M. L. and Souza, D. O., 2003. Effects of undernutrition on glutamatergic parameters in rat brain. Neurochem Res 28, 1181–1186.

    Google Scholar 

  • Russell, S. J. and Kahn, C. R., 2007. Endocrine regulation of aging. Nat Rev: Molec Cell Biol 8, 681–691.

    Article  CAS  Google Scholar 

  • Shi, L., Adams, M. M., Linville, M. C., Newton, I. G., Forbes, M. E., Long, A. B., Riddle, D. R. and Brunso-Bechtold, J. K., 2007. Caloric restriction eliminates the aging-related decline in NMDA and AMPA receptor subunits in the rat hippocampus and induces homeostasis. Exp Neurol 206, 70–79.

    Google Scholar 

  • Shiarella, K. T. and Magnusson, K. R., 1995. Glutamate receptor binding correlates with spatial memory performance in the aging C57Bl mouse. Soc Neurosci 21(237), 5.

    Google Scholar 

  • Stewart, J., Mitchell, J. and 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 Morris water mazes. Neurobiol Aging 10, 669–675.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, R. and Goto, S., 2002. Effect of dietary restriction beyond middle age: accumulation of altered proteins and protein degradation. Microscopy Res Tech 59, 278–281.

    Article  CAS  Google Scholar 

  • Vitousek, K. M., Manke, F. P., Gray, J. A. and Vitousek, M. N., 2004. Caloric restriction for longevity: II-the systematic neglect of behavioural and psychological outcomes in animal research. Eur Eating Disorders Rev 12, 338–360.

    Article  Google Scholar 

  • Weindruch, R. and Walford, R. L., 1988. The Retardation of Aging and Disease by Dietary Restriction, Charles C. Thomas, Springfield, IL.

    Google Scholar 

  • Wu, A., Sun, X. and Liu, Y., 2003. Effects of caloric restriction and behavior in developing mice. Neurosci Lett 339, 166–168.

    Article  PubMed  CAS  Google Scholar 

  • Yanai, S., Okaichi, Y. and Okaichi, H., 2004. Long-term dietary restriction causes negative effects on cognitive functions in rats. Neurobiol Aging 25, 325–332.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA

    Edward L. Spangler, Jeffrey Long, Bennett Kelley-Bell, Marshall Miller & Rafael de Cabo

  2. Aging, Metabolism and Nutrition Unit, Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA

    Robin K. Minor

Authors
  1. Edward L. Spangler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bennett Kelley-Bell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marshall Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robin K. Minor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rafael de Cabo
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Sydney, 2006, Australia

    Arthur V. Everitt

  2. University of Aarhus, University of Aarhus, Aarhus, 8000, Denmark

    Suresh I. S. Rattan

  3. Sydney, 2006, Australia

    David G. le Couteur

  4. National Institute on Aging, Gerontology Research Center, National Institute of Health, Nathan Shock Drive 5600, Baltimore, 21224, USA

    Rafael de Cabo

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Spangler, E.L., Long, J., Kelley-Bell, B., Miller, M., Minor, R.K., de Cabo, R. (2010). Will Calorie Restriction Stave Off Age-Related Brain Dysfunction, Specifically to Learning and Memory? A Review and Critique of the Rodent Literature. In: Everitt, A., Rattan, S., le Couteur, D., de Cabo, R. (eds) Calorie Restriction, Aging and Longevity. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8556-6_10

Download citation

Publish with us

Policies and ethics

Search

Navigation