Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle

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Updated: Aug 6, 2026

Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
10:10

Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans

Published on: February 16, 2017

Erik Edström1, Mikael Altun, Martin Hägglund

  • 1Department of Neuroscience, Karolinska Institutet, Neuroscience, A3:4, Stockholm, Sweden 17177. erik.edstrom@ki.se

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|July 28, 2006
PubMed

Insights

Age-related muscle loss (sarcopenia) differs from other forms of atrophy. Key muscle-degrading proteins Atrogin-1/MAFbx and MuRF1 are downregulated in sarcopenia, contrary to other atrophy conditions.

Area of Science:

  • Muscle physiology
  • Aging research
  • Molecular biology

Background:

  • Muscle atrophy involves ubiquitin E3-ligases like Atrogin-1/MAFbx and MuRF1.
  • These ligases are crucial for protein degradation in muscle wasting conditions.

Purpose of the Study:

  • To investigate the role of Atrogin-1/MAFbx and MuRF1 in age-related muscle loss (sarcopenia).
  • To explore the underlying molecular mechanisms, including AKT and FOXO4 signaling, in sarcopenia.
  • To assess the impact of dietary restriction on sarcopenia and related molecular pathways.

Main Methods:

  • Analysis of Atrogin-1/MAFbx and MuRF1 expression in aged rats.
  • Investigation of AKT and FOXO4 phosphorylation status.
  • Assessment of IGF-1 receptor signaling pathway components (ShcA-Grb2-GAB).
  • Evaluation of dietary restriction effects on molecular markers and muscle mass.

Main Results:

  • Atrogin-1/MAFbx and MuRF1 were downregulated in sarcopenic rat skeletal muscle.
  • Downregulation correlated with increased AKT and FOXO4 phosphorylation, suggesting AKT-mediated FOXO4 inactivation.
  • Insulin-like growth factor-1 (IGF-1) receptor signaling appeared to mediate AKT activation.
  • Dietary restriction attenuated sarcopenia and prevented age-related changes in AKT/FOXO4 phosphorylation and gene regulation.

Conclusions:

  • Sarcopenia exhibits distinct molecular mechanisms compared to acute atrophy (disuse, disease, denervation).
  • Age-related muscle loss is characterized by suppressed, not upregulated, Atrogin-1/MAFbx and MuRF1.
  • AKT/FOXO4 pathway inactivation and IGF-1 signaling are implicated in sarcopenia.
  • Dietary restriction offers a potential intervention strategy against sarcopenia.

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