Language

English

Publication Date

8-1-2026

Journal

Annual Review of Nutrition

DOI

10.1146/annurev-nutr-111225-024640

PMID

42166675

PMCID

PMC13585284

PubMedCentral® Posted Date

9-18-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Preterm birth disrupts nutrient-responsive signaling pathways critical for skeletal muscle growth and long-term metabolic health. Despite improvements in neonatal care, preterm infants often experience postnatal growth failure marked by impaired lean mass accretion. This review examines how prematurity intrinsically alters insulin and amino acid signaling to mechanistic target of rapamycin complex 1 (mTORC1), a central regulator of translation initiation and protein synthesis. Evidence from translational models reveals blunted activation of mTORC1 and its downstream effectors, independent of birth weight or comorbidities. Defects in insulin-PDK1/mTORC2-Akt signaling and amino acid sensing, particularly leucine sensing, contribute to impaired mTORC1-dependent translation initiation and reduced muscle protein synthesis. Feeding strategies that mimic physiological nutrient pulsatility, including intermittent bolus feeding and pulsatile leucine supplementation during continuous feeding, show promise in restoring anabolic signaling. Understanding these molecular impairments provides a foundation for targeted nutritional and therapeutic interventions to improve muscle growth and mitigate long-term health risks in individuals born preterm.

Keywords

Humans, Muscle, Skeletal, Signal Transduction, Infant, Newborn, Protein Biosynthesis, Infant, Premature, Mechanistic Target of Rapamycin Complex 1, Animals, Insulin, Muscle Proteins, Amino Acids, Nutrients, Infant Nutritional Physiological Phenomena

Published Open-Access

yes

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