Document Detail


Combined exercise and insulin-like growth factor-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage.
MedLine Citation:
PMID:  21867412     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Erika Koltai; Zhongfu Zhao; Zsombor Lacza; Attila Cselenyak; Gabriella Vacz; Csaba Nyakas; Istvan Boldogh; Noriko Ichinoseki-Sekine; Zsolt Radak
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-25
Journal Detail:
Title:  Rejuvenation research     Volume:  14     ISSN:  1557-8577     ISO Abbreviation:  Rejuvenation Res     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-19     Completed Date:  2012-04-17     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  101213381     Medline TA:  Rejuvenation Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  585-96     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
AG 021830/AG/NIA NIH HHS; P01 AG021830/AG/NIA NIH HHS; P30 ES006676/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
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; 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; G9481N71RO/Deoxyguanosine
Comments/Corrections

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