Growth factors, aging and age-related diseases

Growth Horm IGF Res. 2016 Jun;28:66-8. doi: 10.1016/j.ghir.2016.01.001. Epub 2016 Jan 7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Caloric Restriction
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism*
  • Diet, Protein-Restricted
  • Growth Hormone / genetics
  • Growth Hormone / metabolism*
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Longevity / genetics
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Receptors, Somatotropin / genetics
  • Receptors, Somatotropin / metabolism*
  • Ribosomal Protein S6 Kinases / genetics
  • Ribosomal Protein S6 Kinases / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Receptors, Somatotropin
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases