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Mitochondrial DNA alterations in aged macrophage migration inhibitory factor-knockout mice

Allen Herbst1, Austin N Hoang2, Wendy Woo2

  • 1Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.

Mechanisms of Ageing and Development
|August 6, 2019
PubMed

Insights

Age-related mitochondrial DNA (mtDNA) deletions contribute to muscle loss. This study found macrophage migration inhibitory factor (MIF) knockout did not reduce mtDNA deletions in aged mice, suggesting MIF is not a key driver of this process.

Area of Science:

  • Gerontology
  • Mitochondrial Biology
  • Muscle Physiology

Background:

  • Age-induced mitochondrial DNA (mtDNA) deletion mutations accumulate exponentially, contributing to muscle fiber loss.
  • Systemic inflammation, often seen in aging, is linked to reduced muscle mass and sporadic mtDNA deletions.
  • Macrophage migration inhibitory factor knockout (MIF-KO) mice exhibit reduced inflammation and extended lifespan.

Purpose of the Study:

  • To investigate the role of macrophage migration inhibitory factor (MIF) in age-induced mitochondrial DNA (mtDNA) deletions.
  • To determine if MIF deficiency reduces mtDNA deletion frequency and electron transport chain (ETC) deficient fibers in aged mice.

Main Methods:

  • Assessed mtDNA copy number and deletion frequency in aged MIF-KO mice and F2 hybrid controls.
  • Quantified the number and length of ETC deficient fibers in these mice.
  • Measured mtDNA copy number and deletion frequency in lifespan-matched UM-HET3 mice.

Main Results:

  • MIF ablation did not significantly affect muscle mtDNA deletion frequency in aged mice.
  • MIF-KO mice and lifespan-matched UM-HET3 mice showed significantly lower mtDNA copy number compared to F2 hybrids.
  • Genetic background plays a crucial role in controlling mtDNA copy number.

Conclusions:

  • The data do not support a definitive role for MIF in age-induced skeletal muscle mtDNA deletions.
  • Further research is needed to elucidate the causes of age-related mtDNA deletions.
  • Genetic factors significantly influence mitochondrial copy number during aging.
Keywords:
Macrophage migration inhibitory factorMitochondrial DNAMutationSkeletal muscle

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