Combined exercise and insulin-like growth factor-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage

Erika Koltai, Zhongfu Zhao, Zsombor Lacza, Attila Cselenyak, Gabriella Vacz, Csaba Nyakas, Istvan Boldogh, Noriko Ichinoseki-Sekine, Zsolt Radak

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Abstract

We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF-1) supplementation (5μg/kg per day) and 6 weeks of exercise training (60% of the maximal oxygen consumption [VO 2 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.

Original languageEnglish (US)
Pages (from-to)585-596
Number of pages12
JournalRejuvenation Research
Volume14
Issue number6
DOIs
StatePublished - Dec 1 2011

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ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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