title: Age-dependent changes in 8-oxoguanine-DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle.
abstract: 8-Oxo-7,8-dihydroguanine (8-oxoG) accumulates in the genome over time and is believed to contribute to the development of aging characteristics of skeletal muscle and various aging-related diseases. Here, we show a significantly increased level of intrahelical 8-oxoG and 8-oxoguanine-DNA glycosylase (OGG1) expression in aged human skeletal muscle compared to that of young individuals. In response to exercise, the 8-oxoG level was lastingly elevated in sedentary young and old subjects, but returned rapidly to preexercise levels in the DNA of physically active individuals independent of age. 8-OxoG levels in DNA were inversely correlated with the abundance of acetylated OGG1 (Ac-OGG1), but not with total OGG1, apurinic/apyrimidinic endonuclease 1 (APE1), or Ac-APE1. The actual Ac-OGG1 level was linked to exercise-induced oxidative stress, as shown by changes in lipid peroxide levels and expression of Cu,Zn-SOD, Mn-SOD, and SIRT3, as well as the balance between acetyltransferase p300/CBP and deacetylase SIRT1, but not SIRT6 expression. Together these data suggest that that acetylated form of OGG1, and not OGG1 itself, correlates inversely with the 8-oxoG level in the DNA of human skeletal muscle, and the Ac-OGG1 level is dependent on adaptive cellular responses to physical activity, but is age independent.
authors.affiliation: Research Institute of Sport Science, Semmelweis University, Budapest H-1123, Hungary. radak@mail.hupe.hu
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Radak
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Bori
authors.forename: Erika
authors.initials: E
authors.lastname: Koltai
authors.forename: Ioannis G
authors.initials: IG
authors.lastname: Fatouros
authors.forename: Athanasios Z
authors.initials: AZ
authors.lastname: Jamurtas
authors.forename: Ioannis I
authors.initials: II
authors.lastname: Douroudos
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Terzis
authors.forename: Michalis G
authors.initials: MG
authors.lastname: Nikolaidis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Chatzinikolaou
authors.forename: Apostolos
authors.initials: A
authors.lastname: Sovatzidis
authors.forename: Shuzo
authors.initials: S
authors.lastname: Kumagai
authors.forename: Hisahi
authors.initials: H
authors.lastname: Naito
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001483:Base Sequence; D045647:DNA Glycosylases / Q000378:metabolism*; D017931:DNA Primers; D015444:Exercise; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases