Editors' ChoiceMetabolism

Hormonal response to energy restriction

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Science Translational Medicine  04 Nov 2015:
Vol. 7, Issue 312, pp. 312ec189
DOI: 10.1126/scitranslmed.aad5505

Insulin-like growth factor–1 (IGF-1) is a hormone that is essential to growth and development during childhood and adolescence. When IGF-1 is dysregulated, such as in Laron syndrome and acromegaly, patients experience altered bone and soft tissue growth. IGF-1 levels peak around puberty and then decline progressively, leading to the hypothesis that dwindling IGF-1 levels underlie age-related diseases. However, the longer lives and lower cancer risk of patients with Laron syndrome (low IGF-1) versus acromegaly (high IGF-1) do not support this notion. Considering that chronic caloric restriction (CR), which reduces cancer and other age-related diseases, has been linked to IGF-1 and corticosterone in rodents. Fontana et al. investigated the role of CR in modulating IGF-1 and other hormonal factors in humans.

Unlike rodents, the effects of caloric restriction are difficult to study in people, owing to the challenges in implementing chronic CR. Fontana and colleagues provide new insights into the effects of CR on the IGF-1 axis and other hormonal factors in humans using blood samples collected from 218 subjects in the CALERIE study; a 2-year randomized controlled trial that was designed to evaluate the effects of a 25% reduction in caloric intake in nonobese individuals. The authors found that there are some important differences between rodents and humans when it comes to the effects of CR on IGF-1. Rodents exhibit decreased IGF-1 and increased corticosterone levels in response to CR, but humans demonstrated no change in IGF-1 levels and a subtle, transient increase in serum cortisol. However, CR did increase IGF-1 binding protein 1, which binds IGF-1 and reduces bioavailability. These new insights reveal that rodents and humans exhibit unique hormonal responses to chronic CR, thus highlighting the need for more carefully controlled studies to understand how nutritional interventions may modulate cancer risk and healthspan in humans.

L. Fontana et al., 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. Aging Cell 10.1111/acel.12400 (2015). [Abstract]

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