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Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Leger, Bertrand, Derave, Wim, De Bock, Katrien, Hespel, Peter and Russell, Aaron P. 2008, Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation, Rejuvenation research, vol. 11, no. 1, pp. 163-175.

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Title Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation
Author(s) Leger, Bertrand
Derave, Wim
De Bock, Katrien
Hespel, Peter
Russell, Aaron P.
Journal name Rejuvenation research
Volume number 11
Issue number 1
Start page 163
End page 175
Publisher Mary Ann Liebert Publishers
Place of publication New Rochelle, N.Y.
Publication date 2008-02-15
ISSN 1549-1684
1557-8577
Summary Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3β/4E-BP1, and muscle atrophy, including TNFα/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 ± 0.2 years) and 16 older (70 ± 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40–45% in the type II muscle fibers. TNFα and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3β were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNFα, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.
Language eng
Field of Research 069999 Biological Sciences not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2008, Mary Ann Liebert Publishers
Persistent URL http://hdl.handle.net/10536/DRO/DU:30017101

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Created: Fri, 14 Aug 2009, 13:49:42 EST