Hormonal
Simultaneous inhibition of MuRF1 and MuRF2 E3 ubiquitin ligases induces synergistic skeletal and cardiac muscle hypertrophy and increases muscle protein synthesis rates.
This research suggests that blocking both MuRF1 and MuRF2 proteins can significantly increase muscle mass and protein synthesis in mice. However, this is a genetic manipulation not currently available or safe for humans, as it also causes severe heart enlargement and early lethality in a large portion of the subjects. It highlights the potential of these proteins as future drug targets for sarcopenia, but current technology does not allow for safe, targeted inhibition in humans.
Double knockout (dKO) mice obtained by the inactivation of all four MuRF1 and MuRF2 alleles developed extreme cardiac and milder skeletal muscle hypertrophy. Muscle hypertrophy in dKO mice was maintained throughout the murine life span and was associated with chronically activated muscle protein synthesis.
Why this rating
High-quality in vivo mouse model data with clear phenotypic outcomes, though translational to humans is not directly tested.
Source
Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2
Christian Witt et al. · The EMBO Journal · 2007
DOI 10.1038/sj.emboj.7601952
More from this paper
- MuRF1 and MuRF2 function cooperatively to downregulate anabolic stretch signals (ANP, MLP) and translational machinery (mTOR pathway) in muscle tissue.Strong
- Inhibition of MuRF1 and MuRF2 prevents age-related body fat accumulation in mice, resulting in a lean phenotype despite increased muscle mass.Good
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