Premature ageing in mice expressing defective mitochondrial DNA polymerase

By A. Trifunovic, A. Wredenberg, M. Falkenberg, J. N. Spelbrink, A. Rovio, C. Bruder, M. Bohlooly-y, S. Gidlöf, A. Oldfors, R. Wibom and 3 more. Nature, 2004

2,696 citations recorded by the source corpus.

Subfields: Clinical Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/85f058eb22445beebcf8aeb41dd4f8dc84b26e57

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In Clinical Biochemistry

1. D. C. Chan
2. Hsiuchen Chen
3. R. Youle
4. M. Beal
5. J. Nunnari
6. R. Scarpulla
7. A. Suomalainen
8. Wen Chen

In Molecular Biology

1. D. C. Chan
2. R. Youle
3. Hsiuchen Chen
4. M. Beal
5. J. Nunnari
6. Douglas C. Wallace
7. A. Suomalainen
8. R. Scarpulla

Citations in the corpus

• Life and death: metabolic rate, membrane composition, and life span of animals. (2007, background): “DNA polymerase enzymes have proofreading and error-correcting facilities, and when this capacity of mitochondrial DNA polymerase was removed in mice, there was a three- to fivefold increase in mitochondrial mutations and a corresponding decreased life span (185, 357).”
• Trends in oxidative aging theories. (2007, background): “generated mice lacking the proofreading activity of PolgA throughout the organism [350].”
• Mitochondrial DNA mutations and human disease. (2010, background): “Alternative and more successful approaches to developing mouse models of mitochondrial disease involve manipulating the nuclear genes that regulate mtDNA maintenance and replication, such as TFAM [176 – 182], POLG ( ‘ Mutator ’ model) [183], and PEO1 (Twinkle; ‘ Deletor ’ model) [184].”
• Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. (2006, background): “Premature aging phenotypes have been described in mice with targeted disruption of genes involved in control of mutation rate, regulation of chromosome and telomere stability, ROS homeostasis, apoptosis, stress responses, and the insulin/IGF pathway (Tyner et al. 2002; Mounkes et al. 2003; Chang et ”
• Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “139,140 143 In yeast and C. elegans , downregulation of mitochondrial autophagy proteins results in mitochondrial damage and a shortening of lifespan.”
• Molecular mechanisms and physiological functions of mitophagy (2021, positive): “Nevertheless, accumulation of excess mtDNA mutations is one of the underlying factors in mammalian aging (Trifunovic et al , 2004; Kujoth et al , 2005), implying that mitophagy may function to eliminate mitochondria with mutated mtDNA and prevent aging.”
• Transcriptional paradigms in mammalian mitochondrial biogenesis and function. (2008, methodology): “Direct experimental support for this model comes from recent studies in which a mtDNA polymerase that is defective in proofreading function was substituted for the normal polymerase in mice (213).”
• Oxidative Stress and the Central Nervous System (2017, positive): “Consequently, the brain, with its rich lipid content, high energy demand, and weak antioxidant capacity becomes an easy target of excessive oxidative insult (Hulbert et al., 2007).”