Effect of caloric restriction on base-excision repair (BER) in the aging rat brain

Glen E. Kisby, Steven G. Kohama, Antoinette Olivas, Mona Churchwell, Daniel Doerge, Edward Spangler, Rafael de Cabo, Donald K. Ingram, Barry Imhof, Gaobin Bao, Yoke W. Kow

    Research output: Contribution to journalArticle

    18 Scopus citations

    Abstract

    Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was ∼1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase β and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE.

    Original languageEnglish (US)
    Pages (from-to)208-216
    Number of pages9
    JournalExperimental Gerontology
    Volume45
    Issue number3
    DOIs
    StatePublished - Mar 2010

    Keywords

    • 8-Oxodeoxyguanosine
    • Apyrimidinic/apurinic endonuclease (APE)
    • DNA ligase III
    • DNA polymerase β
    • Exonuclease
    • Frontal/parietal cortex

    ASJC Scopus subject areas

    • Biochemistry
    • Aging
    • Molecular Biology
    • Genetics
    • Endocrinology
    • Cell Biology

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  • Cite this

    Kisby, G. E., Kohama, S. G., Olivas, A., Churchwell, M., Doerge, D., Spangler, E., Cabo, R. D., Ingram, D. K., Imhof, B., Bao, G., & Kow, Y. W. (2010). Effect of caloric restriction on base-excision repair (BER) in the aging rat brain. Experimental Gerontology, 45(3), 208-216. https://doi.org/10.1016/j.exger.2009.12.003