Aging Inhibits Emergency Angiogenesis and Exacerbates Neuronal Damage by Downregulating DARS2

Dan Liu1, Meilin Weng2, Rui Wang3

  • 1Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, The Heilongjiang Key Laboratory of Anesthesia and Intensive Care Research, Harbin Medical University, Harbin, People's Republic of China.

Abstract

Insights

Aging impairs microglial function and blood vessel repair after stroke by reducing DARS2 expression. This leads to worse brain injury in older individuals, highlighting DARS2's role in recovery.

Area of Science:

  • Neuroscience
  • Vascular Biology
  • Aging Research

Background:

  • Early vascular regeneration is crucial for neurological recovery after ischemic stroke.
  • Aging is associated with decreased M2-like microglia polarization and weakened vascular regeneration.
  • The DARS2 gene, a marker for mitochondrial function, plays a role in M2-like microglia polarization, but its mechanism in aging stroke is unclear.

Purpose of the Study:

  • To investigate the molecular mechanism of DARS2 in microglia-mediated angiogenesis during acute ischemic stroke in elderly individuals.
  • To elucidate the impact of aging on DARS2 expression and its subsequent effects on vascular regeneration and neurological function.

Main Methods:

  • Utilized a murine model of middle cerebral artery occlusion (MCAO) for in vivo studies.
  • Performed behavioral assessments, immunoblotting, and angiogenesis assays (tube formation, chick embryo chorioallantoic membrane).
  • Established a D-galactose-induced cellular senescence model in BV2 microglia.

Main Results:

  • Aging exacerbated acute brain injury post-ischemia-reperfusion, characterized by M1/M2 microglia imbalance and reduced DARS2 protein expression.
  • Aging inhibited angiogenesis and decreased expression of BDNF and VEGFA.
  • DARS2 gene knockout in young microglia mimicked aged microglia phenotypes in vitro.

Conclusions:

  • Aging impedes M2-like microglial polarization by downregulating DARS2 expression.
  • This downregulation impairs emergency angiogenesis in acute ischemic stroke, leading to increased neuronal damage.
  • DARS2 is a key factor in age-related decline of microglial function and vascular repair post-stroke.

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