• Open Access

Protein restriction cycles reduce IGF-1 and phosphorylated Tau, and improve behavioral performance in an Alzheimer's disease mouse model

Authors

  • Edoardo Parrella,

    1. Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author
  • Tom Maxim,

    1. Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author
  • Francesca Maialetti,

    1. Division of Nutrition and Aging, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Lu Zhang,

    1. Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author
  • Junxiang Wan,

    1. Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author
  • Min Wei,

    1. Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author
  • Pinchas Cohen,

    1. Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author
  • Luigi Fontana,

    1. Division of Geriatrics and Nutritional Science, Washington University in St. Louis, St. Louis, MO, USA
    2. Department of Medicine, Salerno University School of Medicine, Salerno, Italy
    3. Healthy Aging Platform, CEINGE Biotecnologie Avanzate, Napoli, Italy
    Search for more papers by this author
  • Valter D. Longo

    Corresponding author
    • Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
    Search for more papers by this author

Correspondence

Valter D. Longo, Longevity Institute, Davis School of Gerontology, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA. Tel.: +1 213 7406212; fax: +1 213 8215714; e-mail: vlongo@usc.edu

Summary

In laboratory animals, calorie restriction (CR) protects against aging, oxidative stress, and neurodegenerative pathologies. Reduced levels of growth hormone and IGF-1, which mediate some of the protective effects of CR, can also extend longevity and/or protect against age-related diseases in rodents and humans. However, severely restricted diets are difficult to maintain and are associated with chronically low weight and other major side effects. Here we show that 4 months of periodic protein restriction cycles (PRCs) with supplementation of nonessential amino acids in mice already displaying significant cognitive impairment and Alzheimer's disease (AD)-like pathology reduced circulating IGF-1 levels by 30–70% and caused an 8-fold increase in IGFBP-1. Whereas PRCs did not affect the levels of β amyloid (Aβ), they decreased tau phosphorylation in the hippocampus and alleviated the age-dependent impairment in cognitive performance. These results indicate that periodic protein restriction cycles without CR can promote changes in circulating growth factors and tau phosphorylation associated with protection against age-related neuropathologies.

Ancillary