Dihydrotestosterone rescues the age-dependent decline in protein synthesis in mouse fast-twitch skeletal muscle fibres

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB140

Poster Communications: Dihydrotestosterone rescues the age-dependent decline in protein synthesis in mouse fast-twitch skeletal muscle fibres

O. E. Wendowski1, G. Mutungi1

1. Department of Medicine, University of East Anglia, Norwich, United Kingdom.

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Sarcopenia (muscle wasting due to old age) is a debilitating condition characterised by the gradual loss of skeletal muscle mass and function that manifests itself predominantly in the elderly. It leads to reduced activity, increased susceptibility to falls and eventually to loss of independence. However, despite its physical and socioeconomic importance, the causes and mechanisms underlying sarcopenia are still poorly understood. Previously, we have shown that treating small skeletal muscle fibre bundles, isolated from young mice, with physiological concentrations of the testosterone metabolite, dihydrotestosterone (DHT), increases amino acid uptake and protein synthesis in fast-twitch fibres (the fibres lost during the development of sarcopenia) (Hamdi and Mutungi, 2011); suggesting that DHT may have therapeutic potential in the management of sarcopenia.The primary aim of this study was to investigate the effects of treating small skeletal muscle fibre bundles isolated from young (~100 day old) and old (~600 day old) female mice with physiological concentrations of DHT on protein synthesis. All the experiments were performed at room temperature (~20°C) using small fibre bundles isolated from the extensor digitorium longus (EDL, a fast-twitch in adult mice) and the soleus (a slow-twitch muscle in adult mice) mice killed as recommended in UK legislation (for summary see Drummond 2009). Two types of experiments were performed. In the first experiment, proteins isolated from the EDL and soleus of young and old mice were probed, using monoclonal antibodies, for the expression of the sodium-coupled neutral amino acid transporter (SNAT) 2 and the L-type amino acid transporter (LAT) 2. In the second experiment, the effects of DHT on protein synthesis was determined using the trichloroacetic acid protein precipitation assay followed by liquid scintillation counting as previously described in Hamdi and Mutungi (2011). The results show that the expression of both amino acid transporters increases with age in both the fast-twitch and the slow-twitch muscle fibres. They also show the presence of a second smaller protein band of ~56kDa that was seen in the muscles of old (>500 days old) and very old (>600 days old) mice only. Ageing led to a reduction in protein synthesis in both fibre types and this could be reversed by treating the fibre bundles with 630pgml1-1 DHT. From these findings we suggest that sarcopenia may be due to decreased protein synthesis caused by lack/reduced bioavailability of DHT.



Where applicable, experiments conform with Society ethical requirements.

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