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Nutritionally essential amino acids and metabolic signaling in aging

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Abstract

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.

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Abbreviations

AA:

Amino acid

Akt/PKB:

Protein kinase B

BCAA:

Branched chain AA

EAA:

Essential AA

4E-BP1:

eIF4E Binding protein

eEf:

Eukaryotic elongation factor

eIF:

Eukaryotic initiation factor

FSR:

Fractional synthetic rate

GβL:

G-protein-β-subunit-like protein

GDP:

Guanosine diphosphate

GTP:

Guanosine triphosphate

hVps34:

Human vacuolar protein sorting 34

IGF-1:

Insulin-like growth factor 1

LRS:

Leucyl-tRNA synthetase

mTOR:

Mammalian target of rapamycin

NEAA:

Nonessential AA

NO:

Nitric oxide

PI3K:

Phosphatidylinositol 3-kinase

Rag:

Ras-related GTPase

Raptor:

Regulatory-associated protein of mTOR

Rheb:

Ras homologue enhanced in brain

S6K1:

p70 ribosomal protein S6 kinase 1

SNP:

Sodium nitroprusside

TSC:

Tuberous sclerosis complex

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Acknowledgments

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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  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA

    E. Lichar Dillon

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Dillon, E.L. Nutritionally essential amino acids and metabolic signaling in aging. Amino Acids 45, 431–441 (2013). https://doi.org/10.1007/s00726-012-1438-0

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  • DOI: https://doi.org/10.1007/s00726-012-1438-0

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