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 journalArticlepeer-review

20 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
Externally publishedYes

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

Fingerprint

Dive into the research topics of 'Effect of caloric restriction on base-excision repair (BER) in the aging rat brain'. Together they form a unique fingerprint.

Cite this