Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle

Daniel Cuthbertson; John Babraj; Graham Leese; Tom Waddell; Philip Atherton; Henning Wackerhage; Peter M. Taylor; Michael J. Rennie

doi:10.1096/fj.04-2640fje

journal article Dec 13, 2004

Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle

Daniel Cuthbertson John Babraj Graham Leese Tom Waddell

Philip Atherton Henning Wackerhage Peter M. Taylor Michael J. Rennie

The FASEB Journal Vol. 19 No. 3 pp. 1-22 · Wiley

View at Publisher Save 10.1096/fj.04-2640fje

Abstract

ABSTRACT

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.

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Metrics

954

Citations

51

References

Details

Published: Dec 13, 2004
Vol/Issue: 19(3)
Pages: 1-22
License: View

Authors

D

Daniel Cuthbertson

Division of Molecular Physiology School of Life Sciences University of Dundee Dundee Scotland UK DD1 4HN; Department of Medicine Ninewells Hospital Medical School Tayside NHS Trust Dundee DD1 9ST

J

John Babraj

Division of Molecular Physiology School of Life Sciences University of Dundee Dundee Scotland UK DD1 4HN

G

Graham Leese

Department of Medicine Ninewells Hospital Medical School Tayside NHS Trust Dundee DD1 9ST

T

Tom Waddell

Division of Molecular Physiology School of Life Sciences University of Dundee Dundee Scotland UK DD1 4HN

P

Philip Atherton

Division of Molecular Physiology School of Life Sciences University of Dundee Dundee Scotland UK DD1 4HN; Department of Biological Sciences University of Central Lancashire Preston PR1 2HE

H

Henning Wackerhage

Division of Molecular Physiology School of Life Sciences University of Dundee Dundee Scotland UK DD1 4HN

P

Peter M. Taylor

Division of Molecular Physiology School of Life Sciences University of Dundee Dundee Scotland UK DD1 4HN

M

Michael J. Rennie

Division of Molecular Physiology School of Life Sciences University of Dundee Dundee Scotland UK DD1 4HN; University of Nottingham School of Biomedical Sciences Division of Clinical Physiology Graduate Entry Medical School City Hospital Derby DE22 3DT United Kingdom

Funding

Wellcome Trust

Biotechnology and Biological Sciences Research Council

National Institutes of Health Award: AR49869

Diabetes UK

Cite This Article

Daniel Cuthbertson, John Babraj, Graham Leese, et al. (2004). Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. The FASEB Journal, 19(3), 1-22. https://doi.org/10.1096/fj.04-2640fje

Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle

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