Dna Damage and Repair

There has been a great deal of interest in the question of whether DNA repair declines with age. Investigators have looked at many conditions of premature and normal aging, and many different types of assays have been used. In general, there seems to be a growing consensus that DNA repair declines slightly with age (see Bohr and Anson). One study reported a 1 percent decline in DNA repair capacity per year with advancing age in individuals (Wei et al.). Attempts to correlate DNA repair capacity of different organisms with maximum life span have been made. Hart and Setlow (1974) demonstrated a linear correlation between the logarithm of life span and the DNA repair capacity in cells from different mammalian species, suggesting that higher DNA repair activity is associated with longer life span. Although these studies document a connection between DNA repair capacity and age, there are also a large number of studies in which no connection between these two parameters were found.

Changes in mitochondrial function with age have been observed in several organisms. Experimental data from many laboratories suggest that the mitochondrial genome indeed accumulates DNA damage with age (Bohr and Anson, 1995).

Since oxidative DNA damage accumulates in mitochondria, changes in mtDNA repair with age have been studied. Initially, mtODE activity in mitochondrial extracts obtained from livers and hearts of rats six, twelve, and twenty-three months old was compared. In contrast to the common notion that DNA repair decreases with age, an increase in mtODE activity with increasing age was found. In both organs, activities at twelve and twenty-three months were significantly higher than at six months (p<0.01) (Souza-Pinto et al.). These results suggest that the changes observed in mtODE activity reflect a specific upregulation of the oxidative DNA damage repair mechanisms. Similar results were obtained when investigating mtODE activity in extracts from mouse liver mitochondria. The activity increased from six to fourteen months of age.