DNA Repair Less Efficient in Older Cells

Along with other cellular changes, aged cells accumulate mutations in both their nuclear and mitochondrial genomes, and they contain increased amounts of oxidatively damaged mutagenic bases such as 7,8-dihydro-8-oxoguanine.

Working with cells from young and old rodents, investigators at the University of Texas Medical Branch (Galveston, USA; www.utmb.edu) found that contrary to expectations the level and activity of 8-oxoguanine-DNA glycosylase (OGG1), responsible for repair of 7,8-dihydro-8-oxoguanine, was higher in the liver mitochondrial extract from old rodents than in that from young ones. This apparent paradox was the subject of their study published September 5, 2003, in the online edition of the Proceedings of the National Academy of Sciences.

The investigators analyzed OGG1 in the mitochondria of young vs old mouse livers, as well as in replicating vs. presenescent human fibroblasts. They found that although the total OGG1 activity was higher in old mitochondria, a large fraction of the enzyme was stuck to the membrane in the precursor form, which could not be translocated to and processed in the mitochondrial matrix. A nearly identical phenomenon was observed with the mitochondrial uracil-DNA glycosylase responsible for repair of mutagenic uracil.
Contributing author Dr. Sankar Mitra, professor in the department of human biological chemistry and genetics of the University of Texas Medical Branch observed, "As we get older, our mitochondria become less efficient.”



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