Amino Acids

, Volume 45, Issue 3, pp 431–441 | Cite as

Nutritionally essential amino acids and metabolic signaling in aging

  • E. Lichar Dillon
Review Article


Aging is associated with a gradual decline in skeletal muscle mass and strength leading to increased risk for functional impairments. Although basal rates of protein synthesis and degradation are largely unaffected with age, the sensitivity of older muscle cells to the anabolic actions of essential amino acids appears to decline. The major pathway through which essential amino acids induce anabolic responses involves the mammalian target of rapamycin (mTOR) Complex 1, a signaling pathway that is especially sensitive to regulation by the branched chain amino acid leucine. Recent evidence suggests that muscle of older individuals require increasing concentrations of leucine to maintain robust anabolic responses through the mTOR pathway. While the exact mechanisms for the age-related alterations in nutritional signaling through the mTOR pathway remain elusive, there is increasing evidence that decreased sensitivity to insulin action, reductions in endothelial function, and increased oxidative stress may be underlying factors in this decrease in anabolic sensitivity. Ensuring adequate nutrition, including sources of high quality protein, and promoting regular physical activity will remain among the frontline defenses against the onset of sarcopenia in older individuals.


Skeletal muscle Protein synthesis Anabolic resistance 



Amino acid


Protein kinase B


Branched chain AA


Essential AA


eIF4E Binding protein


Eukaryotic elongation factor


Eukaryotic initiation factor


Fractional synthetic rate


G-protein-β-subunit-like protein


Guanosine diphosphate


Guanosine triphosphate


Human vacuolar protein sorting 34


Insulin-like growth factor 1


Leucyl-tRNA synthetase


Mammalian target of rapamycin


Nonessential AA


Nitric oxide


Phosphatidylinositol 3-kinase


Ras-related GTPase


Regulatory-associated protein of mTOR


Ras homologue enhanced in brain


p70 ribosomal protein S6 kinase 1


Sodium nitroprusside


Tuberous sclerosis complex



This work was supported, in part, through NIH/NCI RO1 CA127971 (M. Sheffield-Moore, PhD). I thank William J. Durham, PhD and Kathleen M. Randolph, BS for their input during the preparation of this manuscript.


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© Springer-Verlag Wien 2012

Authors and Affiliations

  1. 1.Division of Endocrinology and Metabolism, Department of Internal MedicineThe University of Texas Medical BranchGalvestonUSA

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