Abstract
Skeletal muscle atrophy is a critical component of the ageing process. Age-related muscle wasting is due to disrupted muscle protein turnover, a process mediated in part by the ubiquitin proteasome pathway (UPP). Additionally, older subjects have been observed to have an attenuated anabolic response, at both the molecular and physiological levels, following a single-bout of resistance exercise (RE). We investigated the expression levels of the UPP-related genes and proteins involved in muscle protein degradation in 10 older (60–75 years) vs. 10 younger (18–30 years) healthy male subjects at basal as well as 2 h after a single-bout of RE. MURF1, atrogin-1 and FBXO40, their substrate targets PKM2, myogenin, MYOD, MHC and EIF3F as well as MURF1 and atrogin-1 transcriptional regulators FOXO1 and FOXO3 gene and/or protein expression levels were measured via real time PCR and western blotting, respectively. At basal, no age-related difference was observed in the gene/protein levels of atrogin-1, MURF1, myogenin, MYOD and FOXO1/3. However, a decrease in FBXO40 mRNA and protein levels was observed in older subjects, while PKM2 protein was increased. In response to RE, MURF1, atrogin-1 and FBXO40 mRNA were upregulated in both the younger and older subjects, with changes observed in protein levels. In conclusion, UPP-related gene/protein expression is comparably regulated in healthy young and old male subjects at basal and following RE. These findings suggest that UPP signaling plays a limited role in the process of age-related muscle wasting. Future studies are required to investigate additional proteolytic mechanisms in conjunction with skeletal muscle protein breakdown (MPB) measurements following RE in older vs. younger subjects.
Highlights
Maintaining skeletal muscle mass is a critical component of health and sustaining life
FBXO40 mRNA levels were decreased by 25% in older subjects when compared to younger subjects (p < 0.01)
Age-related muscle atrophy is linked to disrupted protein turnover in muscle protein synthesis (MPS) and muscle protein breakdown (MPB) as well as reduced regenerative capacity (Brack and Rando, 2007)
Summary
Maintaining skeletal muscle mass is a critical component of health and sustaining life. Known substrate targets of MURF1 include pyruvate kinase M2 (PKM2) (Hirner et al, 2008) and myosin heavy chain (MHC) (Clarke et al, 2007; Fielitz et al, 2007; Cohen et al, 2009), whereas known substrate targets of atrogin-1 include elongation initiation factor 3 subunit 5 (EIF3F) (Lagirand-Cantaloube et al, 2008), MYOD (Tintignac et al, 2005) and myogenin (MYOG) (Jogo et al, 2009) These substrate targets are proteins involved in biological processes essential to muscle health and function, such as MPS (EIF3F), www.frontiersin.org
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