Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans

Luigi Fontana, Edward P. Weiss, Dennis T. Villareal, Samuel Klein, John O. Holloszy

Research output: Contribution to journalArticlepeer-review

331 Scopus citations

Abstract

Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF-1 concentration by ∼40%, protects against cancer and slows aging in rodents. However, the long-term effects of CR with adequate nutrition on circulating IGF-1 levels in humans are unknown. Here we report data from two long-term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF-1 and IGF-1: IGFBP-3 ratio levels in humans. In contrast, total and free IGF-1 concentrations were significantly lower in moderately protein-restricted individuals. Reducing protein intake from an average of 1.67 g kg-1 of body weight per day to 0.95 g kg-1 of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194 ng mL-1 to 152 ng mL-1. These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1: IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.

Original languageEnglish
Pages (from-to)681-687
Number of pages7
JournalAging Cell
Volume7
Issue number5
DOIs
StatePublished - 2008

Keywords

  • Aging
  • Calorie restriction
  • IGF-1
  • Metabolism
  • Protein restriction

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