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Aging Cell. 2016 Feb;15(1):22-7. doi: 10.1111/acel.12400. Epub 2015 Oct 6.

Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial.

Author information

1
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
2
Department of Clinical and Experimental Sciences, University of Brescia Medical School, Brescia, Italy.
3
CEINGE Biotecnologie Avanzate, Napoli, Italy.
4
Center for Translational Research on Inflammatory Diseases (CTRID), Baylor College of Medicine, Michael E DeBakey VA Medical Center, Houston, TX, USA.
5
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
6
Pennington Biomedical Research Center, Baton Rouge, LA, USA.
7
Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Sanford Burnham Medical Research Institute, Orlando, FL, USA.
8
Duke Clinical Research Institute, Durham, NC, USA.
9
Rho Federal Systems, Chapel Hill, NC, USA.

Abstract

Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) ) young and middle-aged (20-50 years age range) men and women. Average CR during the first 6 months was 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2-years period of which 71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant 21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF-AB and TGFβ-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significantly and persistently increases serum IGFBP-1 concentration.

KEYWORDS:

IGF-1; IGFBP-1; calorie restriction; cancer; cortisol; weight loss

PMID:
26443692
PMCID:
PMC4717266
DOI:
10.1111/acel.12400
[Indexed for MEDLINE]
Free PMC Article

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