title: Combined exercise and insulin-like growth factor-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage.
abstract: We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF-1) supplementation (5 μg/kg per day) and 6 weeks of exercise training (60% of the maximal oxygen consumption [VO₂ max]) on neurogenesis, DNA damage/repair, and sirtuin content in the hippocampus of young (3 months old) and old (26 months old) rats. Exercise improved the spatial memory of the old group, but IGF-1 supplementation eliminated this effect. An age-associated decrease in neurogenesis was attenuated by exercise and IGF-1 treatment. Aging increased the levels of 8-oxo-7,8-dihydroguanine (8-oxoG) and the protein Ku70, indicating the role of DNA damage in age-related neuropathology. Acetylation of 8-oxoguanine DNA glycosylase (OGG1) was detected in vivo, and this decreased with aging. However, in young animals, exercise and IGF-1 treatment increased acetylated (ac) OGG1 levels. Sirtuin 1 (SIRT1) and SIRT3, as DNA damage-associated lysine deacetylases, were measured, and SIRT1 decreased with aging, resulting in a large increase in acetylated lysine residues in the hippocampus. On the other hand, SIRT3 increased with aging. Exercise-induced neurogenesis might not be a causative factor of increased spatial memory, because IGF-1 plus exercise can induce neurogenesis in the hippocampus of older rats. Data revealed that the age-associated increase in 8-oxoG levels is due to decreased acetylation of OGG1. Age-associated decreases in SIRT1 and the associated increase in lysine acetylation, in the hippocampus, could have significant impact on function and thus, could suggest a therapeutic target.
authors.affiliation: Semmelweis University , Research Institute of Sport Science, Budapest, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Koltai
authors.forename: Zhongfu
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zsombor
authors.initials: Z
authors.lastname: Lacza
authors.forename: Attila
authors.initials: A
authors.lastname: Cselenyak
authors.forename: Gabriella
authors.initials: G
authors.lastname: Vacz
authors.forename: Csaba
authors.initials: C
authors.lastname: Nyakas
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.forename: Noriko
authors.initials: N
authors.lastname: Ichinoseki-Sekine
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Radak
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging; D000818:Animals; D034961:Antigens, Nuclear / Q000096:biosynthesis; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D000072200:Ku Autoantigen; D008297:Male; D018782:Maze Learning; D055495:Neurogenesis; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D007334:Insulin-Like Growth Factor I; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D056566:Sirtuin 3; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen; D003849:Deoxyguanosine