title: Aberrant mitochondrial RNA in the role of aging and aging associated diseases.
abstract: Accumulations of mitochondrial DNA (mtDNA) mutations associated with aging are evident in multiple human tissues. The role of mtDNA mutations can be observed in an aging animal model such as homozygous knock-in PolgA mice, which have a large colonial expansion of mtDNA mutations. They develop reduced lifespan and premature onset of age-related phenotypes, that are also observed in clinical practice like mitochondrial aging acceleration with anti-retroviral therapy through clonal expansion of mtDNA mutations. These clonally expanded mtDNA mutations maintain transcription ability which could result in an accumulation of abnormal mitochondrial RNA (mtRNA) in the affected cells. Compensation-effect doctrine states that accumulated mtDNA mutations in the cell must reach a set threshold before they have a negative effect on cell function due to compensation effects from normal cellular mtDNA. In contrast to this theory, we suggest that an accumulation of aberrant mtRNA transcribed from mtDNA mutations negatively influences cellular function through complex internal and external mitochondrial pathways, and might be an important cause of aging and aging-associated diseases.
authors.affiliation: Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, China; Department of Pediatrics, University of Illinois at Chicago, United States. Electronic address: chenyucaiphd@hotmail.com.
authors.forename: Yucai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, University of Illinois at Chicago, United States.
authors.forename: W Davis
authors.initials: WD
authors.lastname: Parker
authors.affiliation: Department of Pediatrics, University of Illinois at Chicago, United States.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, China.
authors.forename: Kunfang
authors.initials: K
authors.lastname: Yang
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial
chemical_list: D000077278:RNA, Mitochondrial; D012313:RNA