Mitochondrial DNA alterations in aged macrophage migration inhibitory factor-knockout mice
| Autor: | Richard A. Miller, Jonathan Wanagat, David B. Allison, Debbie McKenzie, Judd M. Aiken, Austin Hoang, Allen Herbst, Wendy Woo, Nianjun Liu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Aging Mitochondrial DNA DNA Copy Number Variations Knockout Clinical Sciences Longevity Skeletal muscle Inflammation Biology Systemic inflammation medicine.disease_cause DNA Mitochondrial Article Mice 03 medical and health sciences 0302 clinical medicine Genetics medicine 2.1 Biological and endogenous factors Animals Aetiology Mutation frequency Macrophage Migration-Inhibitory Factors Cellular Senescence Macrophage migration inhibitory factor Mice Knockout Mutation Macrophages DNA Molecular biology Mitochondrial Intramolecular Oxidoreductases 030104 developmental biology medicine.anatomical_structure Knockout mouse medicine.symptom Gerontology 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Mech Ageing Dev |
| ISSN: | 0047-6374 |
| DOI: | 10.1016/j.mad.2019.111126 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect