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Age‐Dependent Accumulation of Mitochondrial DNA Damage in Brain Tissues Derived from Apex1+/− Mice.
Author(s) -
AcevedoTorres Karina,
TorresRamos Carlos A.,
Walter Christi A.,
AyalaTorres Sylvette
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.878.1
Subject(s) - mitochondrial dna , dna damage , lesion , somatic cell , biology , mutation , dna repair , oxidative stress , microbiology and biotechnology , mitochondrion , dna , gene , pathology , genetics , endocrinology , medicine
An age‐dependent accumulation of mutations in both somatic and germ cell tissues has been reported in many organisms. DNA damage induced by oxidative stress has been linked to increases in mutation frequencies. It has been shown that the activity of base excision repair (BER), the main repair mechanism for oxidative DNA damage, declines during aging in mouse brain tissue. The BER enzyme APEX1, may be limiting the repair capacity in aged mice. We sought to test the hypothesis that mtDNA damage increases in an age‐dependent fashion in brain tissues obtained from a BER‐deficient mouse model ( Apex1 +/− ). We measured mtDNA damage by QPCR in 6, 16, and 28‐month‐old wild‐type (WT) and Apex1 +/− mice. Our results show that the frequency of mtDNA lesions in the striatum from 16‐ and 28‐ month old Apex +/ − mice are 0.42 lesions/10kb/strand and 0.53 lesions/10kb/strand, respectively. Cerebral cortex of 28‐month‐old WTand Apex1 +/− mice exhibited a significant increased in lesion number as shown by lesion frequencies of 0.30 lesions/10kb/strand and 0.74 lesions/10kb/strand, respectively. In conclusion, our results show that deficient BER leads to an age‐dependent increase in mtDNA lesions in brain tissues and suggest an important role for BER in mtDNA stability. Supported by R25‐GM061838 and U54‐NS039408.