| Combined exercise and insulin-like growth factor-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage. | |
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MedLine Citation:
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PMID: 21867412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Erika Koltai; Zhongfu Zhao; Zsombor Lacza; Attila Cselenyak; Gabriella Vacz; Csaba Nyakas; Istvan Boldogh; Noriko Ichinoseki-Sekine; Zsolt Radak |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-08-25 |
Journal Detail:
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Title: Rejuvenation research Volume: 14 ISSN: 1557-8577 ISO Abbreviation: Rejuvenation Res Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-19 Completed Date: 2012-04-17 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 101213381 Medline TA: Rejuvenation Res Country: United States |
Other Details:
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Languages: eng Pagination: 585-96 Citation Subset: IM |
Affiliation:
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Semmelweis University , Research Institute of Sport Science, Budapest, Hungary. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging Animals Antigens, Nuclear / biosynthesis DNA Damage DNA Glycosylases / metabolism DNA Repair DNA-Binding Proteins / biosynthesis Deoxyguanosine / analogs & derivatives, pharmacology Hippocampus / metabolism Insulin-Like Growth Factor I / metabolism* Male Maze Learning Neurogenesis Oxygen Consumption Physical Conditioning, Animal* Rats Rats, Wistar Sirtuin 1 / metabolism Sirtuin 3 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AG 021830/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen; 67763-96-6/Insulin-Like Growth Factor I; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 961-07-9/Deoxyguanosine; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/OGG1 protein, rat; EC 3.5.1.-/Sirt1 protein, rat; EC 3.5.1.-/Sirtuin 1; EC 3.5.1.-/Sirtuin 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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