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Mitochondrial DNA alterations in aged macrophage migration inhibitory factor-knockout mice.
Herbst, Allen; Hoang, Austin N; Woo, Wendy; McKenzie, Debbie; Aiken, Judd M; Miller, Richard A; Allison, David B; Liu, Nianjun; Wanagat, Jonathan.
Afiliação
  • Herbst A; Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Hoang AN; Department of Medicine, Division of Geriatrics, UCLA, Los Angeles, CA, USA.
  • Woo W; Department of Medicine, Division of Geriatrics, UCLA, Los Angeles, CA, USA.
  • McKenzie D; Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Aiken JM; Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Miller RA; Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA.
  • Allison DB; Department of Epidemiology and Biostatistics, Indiana University Bloomington, Bloomington, IN, USA.
  • Liu N; Department of Epidemiology and Biostatistics, Indiana University Bloomington, Bloomington, IN, USA.
  • Wanagat J; Department of Medicine, Division of Geriatrics, UCLA, Los Angeles, CA, USA. Electronic address: jwanagat@mednet.ucla.edu.
Mech Ageing Dev ; 182: 111126, 2019 09.
Article em En | MEDLINE | ID: mdl-31381889
The age-induced, exponential accumulation of mitochondrial DNA (mtDNA) deletion mutations contributes to muscle fiber loss. The causes of these mutations are not known. Systemic inflammation is associated with decreased muscle mass in older adults and is implicated in the formation of sporadic mtDNA deletions. Macrophage migration inhibitory factor knockout (MIF-KO) mice are long-lived with decreased inflammation. We hypothesized that aged MIF-KO mice would have lower mtDNA deletion frequencies and fewer electron transport chain (ETC) deficient fibers. We measured mtDNA copy number and mutation frequency as well as the number and length of ETC deficient fibers in 22-month old MIF-KO and F2 hybrid control mice. We also measured mtDNA copy number and deletion frequency in female UM-HET3 mice, a strain whose lifespan matches the MIF-KO mice. We did not observe a significant effect of MIF ablation on muscle mtDNA deletion frequency. There was a significantly lower mtDNA copy number in the MIF-KO mice and the lifespan-matched UM-HET3 mice compared to the F2 hybrids, suggesting the importance of genetic background in mtDNA copy number control. Our data do not support a definitive role for MIF in age-induced mtDNA deletions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA Mitocondrial / Fatores Inibidores da Migração de Macrófagos / Senescência Celular / Oxirredutases Intramoleculares / Variações do Número de Cópias de DNA / Longevidade / Macrófagos Limite: Animals Idioma: En Revista: Mech Ageing Dev Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA Mitocondrial / Fatores Inibidores da Migração de Macrófagos / Senescência Celular / Oxirredutases Intramoleculares / Variações do Número de Cópias de DNA / Longevidade / Macrófagos Limite: Animals Idioma: En Revista: Mech Ageing Dev Ano de publicação: 2019 Tipo de documento: Article