Mitochondrial DNA alterations in aged macrophage migration inhibitory factor-knockout mice. (September 2019)

• Record Type: Journal Article
• Authors: Herbst, Allen; Hoang, Austin N.; Woo, Wendy; McKenzie, Debbie; Aiken, Judd M.; Miller, Richard A.; Allison, David B.; Liu, Nianjun; Wanagat, Jonathan
• Is Part Of: Mechanisms of ageing and development. Volume 182(2019)
• Publication Date: 2019-09
• Subjects: Macrophage migration inhibitory factor -- Mitochondrial DNA -- Mutation -- Skeletal muscle; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2019.111126
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: The origin of age-induced mitochondrial DNA deletions is unknown, but inflammation is implicated. Lifelong MIF ablation does not affect muscle mtDNA deletion frequency as compared to some MIF-intact mice. Aged MIF-KO mice have decreased mtDNA copy number. Inflammation may play other roles in the progression of mtDNA deletions. Abstract: 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.