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.
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.
Field of Research
069999 Biological Sciences not elsewhere classified
Socio Economic Objective
970106 Expanding Knowledge in the Biological Sciences
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