Nutrition, GH/IGF-1 signaling, and cancer

Abstract

Cancer is the second leading cause of death in the United States and among the most prevalent diseases globally, with an incidence expected to grow because of smoking, pollution, poor dietary habits, obesity, and the rise in the older population. Given their ability to reduce risk factors, albeit with varying efficacy, nutrition and fasting could help prevent cancer and other age-related disorders. Calorie restriction (CR), various forms of intermittent fasting (IF) or periodic fasting (PF), and fasting-mimicking diets (FMDs) have been shown to improve health span, increase lifespan, and prevent or postpone cancer in rodents. The effects of specific diets and fasting regimens on aging and cancer appear to be mediated in part by the reduction in the activity of the growth hormone (GH)/insulin-like-growth-factor-I (IGF-1) axis. Nevertheless, recent data indicate that the alternation of low and normal levels of these hormones and factors may be ideal for optimizing longevity and function. Here, we review the role of nutrition, CR, and fasting/FMD on cancer, focusing on the hypothesis that the modulation of GH, IGF-1, and insulin signaling partly mediates the effect of these dietary interventions on cancer prevention.

Figure 1.

Schematic representation of GH/IGF-I axis and nutrient regulation. GHRH, Growth Hormone Release Hormone; SST, Somatostatin; GH, Growth Hormone; IGF-I, Insulin-like Growth Factor I; FFA, Free Fatty Acids; AAs, Amino acids; KB, Ketone bodies. Adapted from “Overview of hypothalamic and anterior pituitary hormones”, by BioRender.com (2023).

Figure 2.

Alterations in the GH/IGF-1 signaling. Under physiological conditions, the anterior pituitary gland releases GH which, binding the GH receptor (GHR) in the liver, leads to IGF-I secretion. (A) In pathological conditions such as acromegaly, the presence of a pituitary adenoma induces excessive secretion of GH by the pituitary gland. The consequent overproduction of IGF-I causes abnormally high linear growth and metabolic dysfunctions. It also correlates with high colon rectal cancer (CRC) incidence. (B) As a result of a GH deficiency (pituitary dwarfism) or GHR mutation (Laron syndrome), the synthesis of IGF-I is reduced in the liver and many other extrahepatic tissues. The abrogation of IGF-I production impairs growth and affects IGF-I function as a negative feedback regulator of GH secretion. It also correlates with a low incidence of cancer. Created with Biorender.com (2023).