A potential impact of DNA repair on ageing and lifespan in the ageing model organism Podospora anserina: decrease in mitochondrial DNA repair activity during ageing.
The free radical theory of ageing states that ROS play a key role in age-related decrease in mitochondrial function via the damage of mitochondrial DNA (mtDNA), proteins and lipids. In the sexually reproducing ascomycete Podospora anserina ageing is, as in other eukaryotes, associated with mtDNA instability and mitochondrial dysfunction. Part of the mtDNA instabilities may arise due to accumulation of ROS induced mtDNA lesions, which, as previously suggested for mammals, may be caused by an age-related decrease in base excision repair (BER). Alignments of known BER protein sequences with the P. anserina genome revealed high homology. We report for the first time the presence of BER activities in P. anserina mitochondrial extracts. DNA glycosylase activities decrease with age, suggesting that the increased mtDNA instability with age may be caused by decreased ability to repair mtDNA damage and hence contribute to ageing and lifespan control in this ageing model. Additionally, we find low DNA glycosylase activities in the long-lived mutants grisea and DeltaPaCox17::ble, which are characterized by low mitochondrial ROS generation. Overall, our data identify a potential role of mtDNA repair in controlling ageing and life span in P. anserina, a mechanism possibly regulated in response to ROS levels.
Soerensen
Mette
M
Danish Centre for Molecular Gerontology and Danish Aging Research Center, Aarhus University, Department of Molecular Biology, University of Aarhus, Aarhus C, Denmark.
Gredilla
Ricardo
R
Müller-Ohldach
Mathis
M
Werner
Alexandra
A
Bohr
Vilhelm A
VA
Osiewacz
Heinz D
HD
Stevnsner
Tinna
T
D000375:Aging; D000595:Amino Acid Sequence; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D048468:Podospora / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D004272:DNA, Mitochondrial; D008055:Lipids; D017382:Reactive Oxygen Species; D045647:DNA Glycosylases