Critical Windows for the Programming Effects of Early-Life Nutrition on Skeletal Muscle Mass

Nestle Nutr Inst Workshop Ser. 2018;89:25-35. doi: 10.1159/000486490. Epub 2018 Jul 10.


Skeletal myogenesis begins in the embryo with proliferation and differentiation of muscle progenitor cells that ultimately fuse to form multinucleated myofibers. After midgestation, muscle growth occurs through hypertrophy of these myofibers. The most rapid growth phase occurs in the perinatal period, resulting in the expansion of muscle mass from 25% of lean mass at birth to 40-45% at maturity. These 2 phases of muscle growth are regulated by distinct molecular mechanisms engaged by extracellular cues and intracellular signaling pathways and regulatory networks they activate. Nutrients influence muscle growth by both providing the necessary substrates and eliciting extracellular cues which regulate the signal transduction pathways that control the anabolic processes of the fibers. The uniquely large capacity of immature myofibers for hypertrophy is enabled by a heightened capacity and sensitivity of protein synthesis to feeding-induced changes in plasma insulin and amino acids, and the ability to expand their myonuclear population through proliferation of muscle precursor cells (satellite cells). With maturation, satellite cells become quiescent, limiting myonuclear accretion, and the capacity of the muscles for protein anabolism progressively diminishes. Therefore, the early developmental phases represent critical windows for muscle growth which, if disrupted, result in muscle mass deficits that are unlikely to be entirely recoverable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amino Acids / blood
  • Animals
  • Cell Differentiation
  • Female
  • Fetal Development / physiology
  • Fetal Nutrition Disorders / physiopathology
  • Humans
  • Hypertrophy
  • Infant
  • Infant Nutrition Disorders / physiopathology
  • Infant Nutritional Physiological Phenomena / physiology
  • Infant, Newborn
  • Insulin / blood
  • Muscle Development / physiology
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / physiology
  • Muscle Proteins / biosynthesis
  • Muscle, Skeletal / embryology*
  • Muscle, Skeletal / growth & development*
  • Nutritional Physiological Phenomena / physiology*
  • Perinatal Care
  • Pregnancy


  • Amino Acids
  • Insulin
  • Muscle Proteins