Source:http://linkedlifedata.com/resource/pubmed/id/19239418
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2009-4-3
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pubmed:abstractText |
The proteins encoded by the Ink4/Arf locus, p16Ink4a, p19Arf and p15Ink4b are major tumour suppressors that oppose aberrant mitogenic signals. The expression levels of the locus are progressively increased during aging and genome-wide association studies have linked the locus to a number of aging-associated diseases and frailty in humans. However, direct measurement of the global impact of the Ink4/Arf locus on organismal aging and longevity was lacking. In this work, we have examined the fertility, cancer susceptibility, aging and longevity of mice genetically modified to carry one (Ink4/Arf-tg) or two (Ink4/Arf-tg/tg) intact additional copies of the locus. First, increased gene dosage of Ink4/Arf impairs the production of male germ cells, and in the case of Ink4/Arf-tg/tg mice results in a Sertoli cell-only-like syndrome and a complete absence of sperm. Regarding cancer, there is a lower incidence of aging-associated cancer proportional to the Ink4/Arf gene dosage. Interestingly, increased Ink4/Arf gene dosage resulted in lower scores in aging markers and in extended median longevity. The increased survival was also observed in cancer-free mice indicating that cancer protection and delayed aging are separable activities of the Ink4/Arf locus. In contrast to these results, mice carrying one or two additional copies of the p53 gene (p53-tg and p53-tg/tg) had a normal longevity despite their increased cancer protection. We conclude that the Ink4/Arf locus has a global anti-aging effect, probably by favouring quiescence and preventing unnecessary proliferation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1474-9726
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
152-61
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pubmed:meshHeading |
pubmed-meshheading:19239418-Aging,
pubmed-meshheading:19239418-Animals,
pubmed-meshheading:19239418-Cell Proliferation,
pubmed-meshheading:19239418-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:19239418-Gene Dosage,
pubmed-meshheading:19239418-Genes, Tumor Suppressor,
pubmed-meshheading:19239418-Immunity, Innate,
pubmed-meshheading:19239418-Infertility, Male,
pubmed-meshheading:19239418-Longevity,
pubmed-meshheading:19239418-Male,
pubmed-meshheading:19239418-Mice,
pubmed-meshheading:19239418-Mice, Inbred C57BL,
pubmed-meshheading:19239418-Mice, Transgenic,
pubmed-meshheading:19239418-Neoplasms,
pubmed-meshheading:19239418-Spermatogenesis,
pubmed-meshheading:19239418-Tumor Suppressor Protein p53
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pubmed:year |
2009
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pubmed:articleTitle |
Anti-aging activity of the Ink4/Arf locus.
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pubmed:affiliation |
Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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