The aging brain: accumulation of DNA damage or neuron loss?

Age-related molecular and cellular alterations in the central nervous system are known to show selectivity for certain cell types and brain regions. Among them age-related accumulation of nuclear (n) DNA damage can lead to irreversible loss of genetic information content. In the present study on the aging mouse brain, we observed a substantial increase in the amount of nDNA single-strand breaks in hippocampal pyramidal and granule cells as well as in cerebellar granule cells but not in cerebellar Purkinje cells. The reverse pattern was found for age-related reductions in total numbers of neurons. Only the total number of cerebellar Purkinje cells was significantly reduced during aging whereas the total numbers of hippocampal pyramidal and granule cells as well as of cerebellar granule cells were not. This formerly unknown inverse relation between age-related accumulation of nDNA damage and age-related loss of neurons may reflect a fundamental process of aging in the central nervous system.