NeuroMolecular Medicine

, Volume 9, Issue 1, pp 17–20

Energy intake and amyotrophic lateral sclerosis

  • Mark P. Mattson
  • Roy G. Cutler
  • Simonetta Camandola


Roy Walford, a physician and scientist who pioneered research on the anti-aging effects of caloric restriction and subjected himself to a low-energy diet, recently died from amyotrophic lateral sclerosis (ALS). Information from his case, epidemiological findings, and recent controlled studies in mouse models of ALS suggest that low-energy diets might render motor neurons vulnerable to degeneration, whereas high-energy diets are ameliorative. This contrasts with the effects of low-energy diets on various neuronal populations in the brain that respond adaptively, activating pathways that promote plasticity and resistance to disease. One reason that motor neurons might be selectively vulnerable to low-energy diets is that they are unable to engage neuroprotective responses to energetic stress response involving the protein chaperones, such as, heat-shock protein-70.

Index Entries

Caloric restriction motor neurons HSP-70 superoxide dismutase oxidative stress ALS 


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  1. Batulan Z., Shinder G. A., Minotti S., et al. (2003) High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1, J. Neurosci. 23, 5789–5798.PubMedGoogle Scholar
  2. Desport J. C., Preux P. M., Truong T. C., Vallat J. M., Sautereau D., and Couratier P. (1999) Nutritional status is a prognostic factor for survival in ALS patients. Neurology 53, 1059–1063.PubMedGoogle Scholar
  3. Desport J. C., Preux P. M., Magy L., et al. (2001) Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am. J. Clin. Nutr. 74, 328–334.PubMedGoogle Scholar
  4. Duan W., Guo Z., Jiang H., Ware M., Li X. J. and Mattson M. P. (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, 2911–2916.PubMedCrossRefGoogle Scholar
  5. Dupuis L., Oudart H., Rene F., Gonzalez de Aguilar J. L., and Loeffler J. P. (2004) Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc. Natl. Acad. Sci. USA 101, 11,159–11,164.CrossRefGoogle Scholar
  6. Hamadeh M. J. Rodriquez M. C., Kaczor J. J., and Tarnopolsky M. A. (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, 214–220.PubMedCrossRefGoogle Scholar
  7. Kasarskis E. J. and Winslow M. (1989) When did Lou Gehrig’s personal illness begin?, Neurology 39, 1243–1245.PubMedGoogle Scholar
  8. Klivenyi P., Ferrante R. J., Matthews R.T., et al. (1999) Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat. Med. 5, 347–350.PubMedCrossRefGoogle Scholar
  9. Kurzke J. F. (1982) Epidemiology of amyotrophic lateral sclerosis. Adv. Neurol. 36, 281–302.Google Scholar
  10. Lassinger B. K. Kwak C., Walford R. L., and Jankovic J. (2004) Atypical parkinsonism and motor neuron syndrome in a Biosphere 2 participant: a possible complication of chronic hypoxia and carbon monoxide toxicity. Movement Disorders 19, 465–469.PubMedCrossRefGoogle Scholar
  11. Majoor-Krakauer D., Willems P. J., and Hofman A. (2003) Genetic epidemiology of amyotrophic lateral sclerosis. Clin. Genet. 63, 83–101.PubMedCrossRefGoogle Scholar
  12. Maswood N., Young J., Tilmont E., et al. (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, 18,171–18,176.CrossRefGoogle Scholar
  13. O’Connor A. (2004) New York Times, May 4, 2004. news_announcements/walford_endowedlecture ship/NYTimes.htm.Google Scholar
  14. Okado-Matsumoto A. and Fridovich I. (2002) Amyotrophic lateral sclerosis: a proposed mechanism. Proc. Natl. Acad. Sci. USA 99, 9010–9014.PubMedGoogle Scholar
  15. Petel N. V., Gordon M. N., Connor K. E., et al. (2005) Caloric restriction attenuates A beta-deposition in Alzheimer transgenic models. Neurobiol. Aging 26, 995–1000.CrossRefGoogle Scholar
  16. Pedersen W. A., and Mattson M. P. (1999) No benefit of dietary restriction on disease onset or progression in amyotrophic lateral sclerosis Cu/Zn-superoxide dismutase mutant mice. Brain Res. 833, 117–120.PubMedCrossRefGoogle Scholar
  17. Scarmeas N., Shih T., Stern Y., Ottman R., and Rowland L. P. (2003) Premorbid weight, body mass, and varsity athletics in ALS. Neurology 59, 773–775.Google Scholar
  18. Sinclair D. A. (2005) Toward a unified theory of caloric restriction and longevity regulation. Mech. Ageing Dev. 126, 987–1002.PubMedCrossRefGoogle Scholar
  19. Veldink J. H., Kalmijn S., Groeneveld G. J., Titulaer M. J., Wokke J. H., and van den Berg L. H. (2005) Physical activity and the association with sporadic ALS. Neurology 64, 241–245.PubMedGoogle Scholar
  20. Walford R. L. (1985) The extension of maximum life span. Clin. Geriatr. Med. 1, 29–35.PubMedGoogle Scholar
  21. Walford R. L., Mock D., Verdery R., and MacCallum T. (2002) Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J. Gerontol. A Biol. Sci. Med. Sci. 57, B211-B224.PubMedGoogle Scholar
  22. Yu Z. F. and Mattson M. P. (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, 830–839.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2007

Authors and Affiliations

  • Mark P. Mattson
    • 1
  • Roy G. Cutler
    • 1
  • Simonetta Camandola
    • 1
  1. 1.Laboratory of NeurosciencesNational Institute on Aging Intramural Research ProgramBaltimore

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