Growth factors, aging and age-related diseases

Abstract

Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases.

Keywords: Amino acids; Calorie restriction; Growth; Growth hormone; Growth hormone receptor deficiency; IGF-1; Proteins; Ras; TOR.

Conflict of interest statement

Conflict of interest

VDL has equity interests in DSR Pharma Inc. VDL and PB have filed provisional patents related to the development of GHR blockers.

Copyright © 2016 Elsevier Ltd. All rights reserved.

Figures

Figure 1

A model for conserved nutrient signaling pathways that regulate aging Dietary restriction reduces the activity of conserved pro-aging genes and pathways directly by downregulating TOR and RAS-PKA (yeast), and indirectly, through reduced levels of IGF-1 and Ins/IGF-1 like growth factors (C. elegans, Drosophila and mice). This results in increased expression and/or activity of stress resistance genes that promote lifespan extension.