Molecular and Cellular Biochemistry

, Volume 412, Issue 1–2, pp 59–72 | Cite as

Effects of ageing on expression of the muscle-specific E3 ubiquitin ligases and Akt-dependent regulation of Foxo transcription factors in skeletal muscle

  • Akira Wagatsuma
  • Masataka Shiozuka
  • Yuzo Takayama
  • Takayuki Hoshino
  • Kunihiko Mabuchi
  • Ryoichi Matsuda


Controversy exists as to whether the muscle-specific E3 ubiquitin ligases MAFbx and MuRF1 are transcriptionally upregulated in the process of sarcopenia. In the present study, we investigated the effects of ageing on mRNA/protein expression of muscle-specific E3 ubiquitin ligases and Akt/Foxo signalling in gastrocnemius muscles of female mice. Old mice exhibited a typical sarcopenic phenotype, characterized by loss of muscle mass and strength, decreased amount of myofibrillar proteins, incidence of aberrant muscle fibres, and genetic signature to sarcopenia. Activation levels of Akt were lower in adult and old mice than in young mice. Consequently, Akt-mediated phosphorylation levels of Foxo1 and Foxo3 proteins were decreased. Nuclear levels of Foxo1 and Foxo3 proteins showed an overall increasing trend in old mice. MAFbx mRNA expression was decreased in old mice relative to adult mice, whereas MuRF1 mRNA expression was less affected by ageing. At the protein level, MAFbx was less affected by ageing, whereas MuRF1 was increased in old mice relative to adult mice, with ubiquitin–protein conjugates being increased with ageing. In conclusion, we provided evidence for no mRNA upregulation of muscle-specific E3 ubiquitin ligases and disconnection between their expression and Akt/Foxo signalling in sarcopenic mice. Their different responsiveness to ageing may reflect different roles in sarcopenia.


Ageing MAFbx MuRF1 Muscle wasting Sarcopenia 



This research was supported by MEXT (the Ministry of Education, Culture, Sports, Science and Technology) (Grant in Aid for Scientific Research (C), 25350882), Japan.

Compliance with ethical standards

Conflict of interest

The authors of this manuscript do not have any conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Akira Wagatsuma
    • 1
  • Masataka Shiozuka
    • 2
  • Yuzo Takayama
    • 1
    • 3
  • Takayuki Hoshino
    • 1
  • Kunihiko Mabuchi
    • 1
  • Ryoichi Matsuda
    • 2
  1. 1.Department of Information Physics and Computing, Graduate School of Information Science and TechnologyThe University of TokyoTokyoJapan
  2. 2.Department of Life Sciences, Graduate School of Arts and SciencesThe University of TokyoTokyoJapan
  3. 3.Biotechnology Research Institute for Drug DiscoveryNational Institute of Advanced Industrial Science and Technology (AIST)IbarakiJapan

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