http://www.cnr.it/ontology/cnr/individuo/prodotto/ID218878
Prolonged Lifespan with Enhanced Exploratory Behavior in Mice Overexpressing the Oxidized Nucleoside Triphosphatase hMTH1. (Articolo in rivista)
- Type
- Label
- Prolonged Lifespan with Enhanced Exploratory Behavior in Mice Overexpressing the Oxidized Nucleoside Triphosphatase hMTH1. (Articolo in rivista) (literal)
- Anno
- 2013-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1111/acel.12094 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- De Luca G.; Ventura I.; Sanghez V.; Russo M.T.;Ajmone-Cat MA.; Cacci E.; Martire A.; Popoli P.; Falcone G.; Michelini F.; Crescenzi M.; Degan P.; Minghetti L.; Bignami M.; Calamandrei G. (literal)
- Rivista
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Roma, Italy (GDL, IV, MTR, MB, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Roma, Italy (VS, MAA-C; FM, MC, LM, GC),
Department of Drug Safety and Evaluation, Istituto Superiore di Sanita, Roma, Italy (EC),
Department of Biology and Biotechnology \"Charles \"Darwin\", Sapienza University, Roma, Italy (AM)
Institute of Cell Biology and Neurobiology, National Research Council, Monterotondo, Italy (GF).
Centro di Biotecnologie Avanzate, IST - Istituto Nazionale per la Ricerca sul Cancro, Genova (PD) (literal)
- Titolo
- Prolonged Lifespan with Enhanced Exploratory Behavior in Mice Overexpressing the Oxidized Nucleoside Triphosphatase hMTH1. (literal)
- Abstract
- The contribution that oxidative damage to DNA and/or RNA makes to the aging process remains undefined. In this study we used the hMTH1-Tg mouse model to investigate how oxidative damage to nucleic acids affects aging. hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxodGTP and 8-oxoGTP and excludes 8-oxoguanine from both DNA and RNA. Compared to wild-type animals, hMTH1-overexpressing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in wild-type mice. These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates. Neither lipid oxidation nor overall antioxidant status are significantly affected by hMTH1 overexpression. At the cellular level, neurospheres derived from adult hMTH1-Tg neural progenitor cells display increased proliferative capacity and primary fibroblasts from hMTH1-Tg embryos do not undergo overt senescence in vitro. The significantly lower levels of oxidized DNA/RNA in transgenic animals are associated with behavioral changes. These mice show reduced anxiety and enhanced investigation of environmental and social cues. Longevity conferred by overexpression of a single nucleotide hydrolase in hMTH1-Tg animals is an example of lifespan extension associated with healthy aging. It provides a link between aging and oxidative damage to nucleic acids. (literal)
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