title: 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.
authors.affiliation: Longevity Institute, Davis School of Gerontology, University of Southern California, Los Angeles, California, United States.
authors.forename: Priya
authors.initials: P
authors.lastname: Balasubramanian
authors.affiliation: Longevity Institute, Davis School of Gerontology, University of Southern California, Los Angeles, California, United States; IFOM, FIRC Institute of Molecular Oncology, Milano, Italy. Electronic address: vlongo@usc.edu.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D018753:Diet, Protein-Restricted; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases
keywords: Amino acids; Calorie restriction; Growth; Growth hormone; Growth hormone receptor deficiency; IGF-1; Proteins; Ras; TOR