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Role of Fyn and the interleukin-6-STAT-3-autophagy axis in sarcopenia

Tsuyoshi Sasaki1, Eijiro Yamada2, Ryota Uehara2

  • 1Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.

Iscience
|September 25, 2023
PubMed

Insights

Fyn protein regulates muscle loss in sarcopenia by impacting IL-6 and STAT3 signaling, which affects autophagy. Targeting this axis may offer new therapeutic strategies for sarcopenia.

Area of Science:

  • Muscle physiology
  • Cellular biology
  • Molecular mechanisms of aging

Background:

  • Sarcopenia is characterized by progressive muscle mass loss.
  • The Fyn-STAT3 pathway is implicated in regulating autophagy.
  • Inflammation's role in sarcopenia requires further elucidation.

Purpose of the Study:

  • To investigate the mechanisms linking inflammation, Fyn-STAT3 signaling, and autophagy in sarcopenia.
  • To explore the role of Fyn in the IL-6-STAT3-autophagy axis in mouse models of sarcopenia.

Main Methods:

  • Utilized tail suspension and sciatic denervation mouse models for primary and secondary sarcopenia.
  • Compared gene and protein expression (Fyn, IL-6, STAT3) and autophagic activity in wild-type and Fyn-null mice.

Main Results:

  • In wild-type mice, sarcopenia models showed increased Fyn, IL-6, and phosphorylated STAT3, with abolished autophagy.
  • Fyn-null mice under tail suspension maintained autophagy and reduced STAT3 phosphorylation, despite increased IL-6.

Conclusions:

  • Fyn is a key regulator of the IL-6-STAT3-autophagy axis in sarcopenia.
  • Understanding this pathway provides insights into sarcopenia-associated metabolic diseases.
  • This axis presents a potential target for therapeutic interventions in sarcopenia.
Keywords:
Biological sciencesDisease

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