Age-related changes in DNA repair illuminate the connection between age and genetic damage
Researchers have uncovered a new way in which the aging process is linked to DNA damage--which occurs normally as a result of cell metabolism and environmental influences--and the various ways in which cells repair that damage. In the new work, researchers found that cells in young fruit flies make use of a different mix of molecular DNA-repair mechanisms compared to cells in older flies. The findings are reported by William Engels and colleagues at the University of Wisconsin and appear in the October 24th issue of the journal Current Biology, published by Cell Press.
DNA repair is essential for the accurate preservation of genetic information and to ensure the healthy functioning of cells, and a connection between aging and DNA damage has long been suspected. One line of evidence supporting the connection is that defects in certain genes needed for DNA repair produce maladies that mimic those of accelerated aging. In humans and other mammals, these effects include elevated occurrence of malignancies, osteoporosis, hearing loss, graying of hair, and hair loss. It is also known that DNA damage accumulates with age in cells of a variety of tissue types.
Breaks in the DNA chain have a variety of causes and occur frequently in the course of natural cellular processes. Repairing such breaks is an essential but hazardous process, often leaving missing or added bases at the point of repair. Cells possess a variety of methods for repairing broken DNA, and the cell's "choice" of how to repair a particular break can be critical. Some repair methods are simple but error prone, whereas the more accurate methods have elaborate molecular requirements and are probably much slower.
The new results show that the reproductive cells of young flies tend to use the rough-and-ready repair processes that do not involve extensive DNA synthesis and do not require a matching DNA template for the repair. As the organisms age, however, the same kind of DNA breaks are repaired primarily by the slower but much more accurate methods that make use of a matching template. These findings raise the question of whether the rapid but risky methods of DNA repair used by cells of young individuals contribute to the accumulation of genetic damage, and perhaps to the aging process itself. Older cells may use the safer repair methods, but they still carry the genetic damage incurred during DNA repair in the fly's "reckless" youth.
The researchers include Christine R. Preston, Carlos Flores, and William R. Engels of the University of Wisconsin in Madison, Wisconsin. This work was supported by National Institutes of Health GM30948.
Preston et al.: "Age-Dependent Usage of Double-Strand Break Repair Pathways." Publishing in Current Biology 16, 2009–2015, October 24, 2006 DOI 10.1016/j.cub.2006.08.058. www.current-biology.com
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