DNA damage during aging of mouse myocardium.
It is not known if DNA lesions, such as covalently modified nucleotides, change qualitatively or quantitatively during aging of post-mitotic cells. If genetic damage accumulates faster than cellular systems can repair it, a cell will eventually become defective in maintaining homeostatis. This situation would be particularly serious for cells that do not divide after they have differentiated to their terminal forms, for example, heart muscle cells. To examine this possibility a 32P-postlabeling technique was used to measure the relative level of modified nucleotides in mouse myocardial DNA as a function of age. The postlabeling analysis indicated that a modified nucleotide changed in an age-dependent manner. A nucleotide with similar chromatographic properties was induced by N-methyl-N-nitrosourea (MNU) alkylation of synthetic polydeoxynucleotides containing the base guanine but not by alkylation of synthetic DNAs lacking this base. This modified nucleotide was found to increase about 9-fold in heart DNA between 2 months and 39 months. These results suggest that the steady-state level of this type of genomic damage is greatly elevated in senescent mouse heart tissue.
D000375:Aging; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D003854:Deoxyribonucleotides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*
D003854:Deoxyribonucleotides