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

Aging Cell

Edoardo Parrella¹  Tom Maxim¹  Francesca Maialetti²  Lu Zhang¹  Junxiang Wan¹  Min Wei¹  Pinchas Cohen¹  Luigi Fontana³ 

[1] Longevity Institute, Davis School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA;Division of Nutrition and Aging, Istituto Superiore di Sanità, Rome, Italy;Division of Geriatrics and Nutritional Science, Washington University in St. Louis, St. Louis, MO, USA

关键词: aging;    alzheimer;    IGF‐1;    IGFBP‐1;    protein restriction;    tau;   

DOI  :  10.1111/acel.12049

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland