Prolonged lifespan with enhanced exploratory behavior in mice overexpressing the oxidized nucleoside triphosphatase hMTH1
Language: 
English
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 is 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.

Author(s): 
De Luca, Gabriele
Ventura, Ilenia
Sanghez, Valentina
Russo, Maria Teresa
Ajmone-Cat, Maria Antonietta
Cacci, Emanuele
Martire, Alberto
Popoli, Patrizia
Falcone, Germana
Michelini, Flavia
Crescenzi, Marco
Degan, Paolo
Minghetti, Luisa
Bignami, Margherita
Calamandrei, Gemma
Item Type: 
Journal Article
Publication Title: 
Aging Cell
Journal Abbreviation: 
Aging Cell
Publication Date: 
2013-08
Publication Year: 
2013
Pages: 
695-705
Volume: 
12
Issue: 
4
ISSN: 
1474-9726
DOI: 
10.1111/acel.12094
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23648059

Turabian/Chicago Citation

Gabriele De Luca, Ilenia Ventura, Valentina Sanghez, Maria Teresa Russo, Maria Antonietta Ajmone-Cat, Emanuele Cacci, Alberto Martire, Patrizia Popoli, Germana Falcone, Flavia Michelini, Marco Crescenzi, Paolo Degan, Luisa Minghetti, Margherita Bignami and Gemma Calamandrei. 2013-08. "Prolonged lifespan with enhanced exploratory behavior in mice overexpressing the oxidized nucleoside triphosphatase hMTH1." Aging Cell 12: 4: 695-705. 10.1111/acel.12094.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1111/acel.12094 | issn = 1474-9726 | volume = 12 | pages = 695-705 | last = De Luca | first = Gabriele | coauthors = Ventura, Ilenia, Sanghez, Valentina, Russo, Maria Teresa, Ajmone-Cat, Maria Antonietta, Cacci, Emanuele, Martire, Alberto, Popoli, Patrizia, Falcone, Germana, Michelini, Flavia, Crescenzi, Marco, Degan, Paolo, Minghetti, Luisa, Bignami, Margherita, Calamandrei, Gemma | title = Prolonged lifespan with enhanced exploratory behavior in mice overexpressing the oxidized nucleoside triphosphatase hMTH1 | journal = Aging Cell | date = 2013-08 | pmid = | pmc = }} </ref>