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Updated: Jun 20, 2025

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

Published on: February 16, 2017

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mtDNA release promotes cGAS-STING activation and accelerated aging of postmitotic muscle cells

Ying Li1, Jie Cui1, Lei Liu1

  • 1School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Key Lab for Rare & Uncommon Diseases of Shandong Province, Jinan, Shandong, China.

Cell Death & Disease
|July 22, 2024
PubMed

Insights

Cellular senescence in aging muscle involves innate immune signaling. This study reveals that mitochondrial DNA release and VDAC1 oligomerization activate cGAS-STING, driving senescence in Zmpste24-/- mice.

Area of Science:

  • Muscle biology
  • Immunology
  • Aging research

Background:

  • The mechanisms of cellular senescence in postmitotic muscle cells remain unclear.
  • cGAS-STING innate immune signaling is implicated in senescence in other cell types but not yet in muscle cells.

Purpose of the Study:

  • To investigate the role of cGAS-STING signaling in cellular senescence of postmitotic muscle cells in a mouse model of Hutchinson-Gilford progeria syndrome (HGPS).

Main Methods:

  • Analysis of myofibers from Zmpste24-/- progeria aged mice.
  • Assessment of senescence-associated phenotypes, mitochondrial DNA (mtDNA) damage, and SASP factor secretion.
  • Investigation of mitophagy, cGAS-STING activation, and VDAC1 oligomerization.
  • Pharmacological inhibition of VDAC1 oligomerization using VBIT4.

Main Results:

  • Zmpste24-/- myofibers exhibited senescence phenotypes, increased mtDNA damage, and SASP factor secretion.
  • Increased mtDNA release, mitophagy dysfunction, and cGAS-STING activation were observed in Zmpste24-/- myofibers.
  • mtDNA release correlated with VDAC1 oligomerization, and VBIT4 treatment reduced mtDNA release, cGAS-STING activation, and SASP factor expression.

Conclusions:

  • A novel mechanism linking innate immune activation to cellular senescence in postmitotic muscle cells of aged muscle was identified.
  • This pathway involves mtDNA release, VDAC1 oligomerization, and cGAS-STING activation.
  • Findings may inform diagnostic markers and therapeutic targets for progeria aging and age-related muscle diseases.

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