Age-associated structural alterations in senescent mouse brain DNA

Abstract

The maintenance of structural integrity in the DNA of aging mice has been examined with the aim in view of determining whether changes in genome structure constitute the molecular basis of aging. Cell lysate DNA from brains of differently aged mice was subjected to alkaline sucrose gradient sedimentation. The results show that brain DNA from young mice sediments monodispersely while that from senescent mice exhibits polydisperse sedimentation patterns, banding in four peaks corresponding to number-average molecular weights of 1.4 [middle dot] 108, 70 [middle dot] 106, 15 [middle dot] 106 and 3 [middle dot] 106.When treated with nuclease S1, it was the 30 month mouse DNA whose sedimentation shifted to the top of the gradient indicating a reduction in its molecular weight as a result of nuclease digestion. The apparent increase in single strand breaks implies that the rate of breakage in old mouse brain DNA is faster than that of repair replication. The conclusion is drawn that senescence could result from an accumulation of defects in the genome.