Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle
| Autor: | M. J. Rennie, Graham P. Leese, T Waddell, Philip J. Atherton, Henning Wackerhage, Daniel J. Cuthbertson, Peter M. Taylor, John A. Babraj, Kenneth Smith |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Aging medicine.medical_specialty Anabolism medicine.medical_treatment Drinking Drug Resistance Muscle Proteins 030209 endocrinology & metabolism P70-S6 Kinase 1 Biochemistry 03 medical and health sciences 0302 clinical medicine Leucine Internal medicine Genetics medicine Humans Eukaryotic Initiation Factors Muscle Skeletal Molecular Biology Aged 030304 developmental biology Carbon Isotopes 0303 health sciences biology TOR Serine-Threonine Kinases Insulin NF-kappa B Ribosomal Protein S6 Kinases 70-kDa medicine.disease Keto Acids Solutions Kinetics Insulin receptor Endocrinology Metabolic window Sarcopenia eIF2B biology.protein Amino Acids Essential Protein Kinases Signal Transduction Biotechnology |
| Zdroj: | The FASEB Journal. 19:1-22 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | The nature of the deficit underlying age-related muscle wasting remains controversial. To test whether it could be due to a poor anabolic response to dietary amino acids, we measured the rates of myofibrillar and sarcoplasmic muscle protein synthesis (MPS) in 44 healthy young and old men, of similar body build, after ingesting different amounts of essential amino acids (EAA). Basal rates of MPS were indistinguishable, but the elderly showed less anabolic sensitivity and responsiveness of MPS to EAA, possibly due to decreased intramuscular expression, and activation (phosphorylation) after EAA, of amino acid sensing/signaling proteins (mammalian target of rapamycin, mTOR; p70 S6 kinase, or p70(S6k); eukaryotic initiation factor [eIF]4BP-1; and eIF2B). The effects were independent of insulin signaling since plasma insulin was clamped at basal values. Associated with the anabolic deficits were marked increases in NFkappaB, the inflammation-associated transcription factor. These results demonstrate first, EAA stimulate MPS independently of increased insulin availability; second, in the elderly, a deficit in MPS in the basal state is unlikely; and third, the decreased sensitivity and responsiveness of MPS to EAA, associated with decrements in the expression and activation of components of anabolic signaling pathways, are probably major contributors to the failure of muscle maintenance in the elderly. Countermeasures to maximize muscle maintenance should target these deficits. |
| Databáze: | OpenAIRE |
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