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

Aging Cell. 2013 Apr;12(2):257-68. doi: 10.1111/acel.12049. Epub 2013 Mar 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / metabolism*
  • Alzheimer Disease / blood
  • Alzheimer Disease / diet therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / blood
  • Animals
  • Cognition / physiology
  • Diet, Protein-Restricted / methods*
  • Disease Models, Animal
  • Gene Expression
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / blood*
  • Insulin-Like Growth Factor Binding Protein 1 / genetics
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mice
  • Phosphorylation
  • tau Proteins / blood*
  • tau Proteins / genetics

Substances

  • Amyloid beta-Peptides
  • Insulin-Like Growth Factor Binding Protein 1
  • insulin-like growth factor-1, mouse
  • tau Proteins
  • Insulin-Like Growth Factor I