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Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle
Author(s) -
Cuthbertson Daniel,
Smith Kenneth,
Babraj John,
Leese Graham,
Waddell Tom,
Atherton Philip,
Wackerhage Henning,
Taylor Peter M.,
Rennie Michael J.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2640fje
Subject(s) - anabolism , p70 s6 kinase 1 , endocrinology , medicine , pi3k/akt/mtor pathway , mechanistic target of rapamycin , amino acid , protein kinase b , wasting , insulin resistance , basal (medicine) , wasting syndrome , biology , phosphorylation , signal transduction , insulin , microbiology and biotechnology , biochemistry
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 NFκB, 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.