title: Perspective: The Potential Role of Essential Amino Acids and the Mechanistic Target of Rapamycin Complex 1 (mTORC1) Pathway in the Pathogenesis of Child Stunting.
abstract: Stunting is the best summary measure of chronic malnutrition in children. Approximately one-quarter of children under age 5 worldwide are stunted. Lipid-based or micronutrient supplementation has little to no impact in reducing stunting, which suggests that other critical dietary nutrients are missing. A dietary pattern of poor-quality protein is associated with stunting. Stunted children have significantly lower circulating essential amino acids than do nonstunted children. Inadequate dietary intakes of essential amino acids could adversely affect growth, because amino acids are required for synthesis of proteins. The master growth regulation pathway, the mechanistic target of rapamycin complex 1 (mTORC1) pathway, is exquisitely sensitive to amino acid availability. mTORC1 integrates cues such as nutrients, growth factors, oxygen, and energy to regulate growth of bone, skeletal muscle, nervous system, gastrointestinal tract, hematopoietic cells, immune effector cells, organ size, and whole-body energy balance. mTORC1 represses protein and lipid synthesis and cell and organismal growth when amino acids are deficient. Over the past 4 decades, the main paradigm for child nutrition in developing countries has been micronutrient malnutrition, with relatively less attention paid to protein. In this Perspective, we present the view that essential amino acids and the mTORC1 pathway play a key role in child growth. The current assumption that total dietary protein intake is adequate for growth among most children in developing countries needs re-evaluation.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD; rdsemba@jhmi.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, St. Louis, MO;
authors.forename: Indi
authors.initials: I
authors.lastname: Trehan
authors.affiliation: National Institute on Aging, NIH, Baltimore, MD;
authors.forename: Marta
authors.initials: M
authors.lastname: Gonzalez-Freire
authors.affiliation: Sight and Life, Basel, Switzerland; and Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kraemer
authors.affiliation: National Institute on Aging, NIH, Baltimore, MD;
authors.forename: Ruin
authors.initials: R
authors.lastname: Moaddel
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, St. Louis, MO;
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Ordiz
authors.affiliation: National Institute on Aging, NIH, Baltimore, MD;
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, St. Louis, MO;
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Manary
mesh_terms: D000601:Amino Acids, Essential / Q000097:blood / Q000172:deficiency*; D001827:Body Height; D002648:Child; D002664:Child Nutritional Physiological Phenomena; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage*; D006130:Growth Disorders / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D044342:Malnutrition / Q000150:complications* / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000601:Amino Acids, Essential; D004044:Dietary Proteins; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: amino acids; children; diet; food; growth; mTORC1; proteins; stunting