title: Effect of caloric restriction on base-excision repair (BER) in the aging rat brain.
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 approximately 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 beta 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.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, OR 97239, USA. kisby@ohsu.edu
authors.forename: Glen E
authors.initials: GE
authors.lastname: Kisby
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kohama
authors.forename: Antoinette
authors.initials: A
authors.lastname: Olivas
authors.forename: Mona
authors.initials: M
authors.lastname: Churchwell
authors.forename: Daniel
authors.initials: D
authors.lastname: Doerge
authors.forename: Edward
authors.initials: E
authors.lastname: Spangler
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: Donald K
authors.initials: DK
authors.lastname: Ingram
authors.forename: Barry
authors.initials: B
authors.lastname: Imhof
authors.forename: Gaobin
authors.initials: G
authors.lastname: Bao
authors.forename: Yoke W
authors.initials: YW
authors.lastname: Kow
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D031204:Caloric Restriction; D004249:DNA Damage; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase