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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

item SEMBA, RICHARD - Johns Hopkins University School Of Medicine
item TREHAN, INDI - Washington University
item GONZALEZ-FREIRE, MARTA - National Institute On Aging (NIA, NIH)
item KRAEMER, KLAUS - Sight & Life
item MOADDEL, RUIN - National Institute On Aging (NIA, NIH)
item ORDIZ, M - Washington University
item FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH)
item MANARY, MARK - Children'S Nutrition Research Center (CNRC)

Submitted to: Advances in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2016
Publication Date: 9/15/2016
Citation: Semba, R.D., Trehan, I., Gonzalez-Freire, M., Kraemer, K., Moaddel, R., Ordiz, M.I., Ferrucci, L., Manary, M.J. 2016. Perspective: The potential role of essential amino acids and the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the pathogenesis of child stunting. Advances in Nutrition. 7(5):853-865.

Interpretive Summary: One quarter of children under the age of 5 are stunted and the assumption has been that there is adequate protein intake among these children pushing major efforts for micronutrients supplementation; unfortunately, micronutrient supplementation has shown little to no effect on stunting, suggesting that some important nutrients are still lacking. This research presents evidence that proposes stunted children have an inadequate intake of essential amino acids which is like to negatively affect specific growth processes associated with, the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway (an on/off switch for growth). This work presents a possible hypothesis that if essential amino acids and their necessity for mTORC1 signaling have a critical role in linear growth of children than evaluation of dietary protein consumption and quality needs to be further assessed for adequacy within this population.

Technical 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.