Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice

被引：334

作者：

Tomas-Loba, Antonia ^{[1
,4
]}

Flores, Ignacio ^{[1
,4
]}

Fernandez-Marcos, Pablo J. ^{[2
]}

Cayuela, Maria L. ^{[1
]}

Maraver, Antonio ^{[2
]}

Tejera, Agueda ^{[1
]}

Borras, Consuelo ^{[3
]}

Matheu, Ander ^{[2
]}

Klatt, Peter ^{[1
,2
]}

Flores, Juana M.

Vina, Jose ^{[3
]}

Serrano, Manuel ^{[2
]}

Blasco, Maria A. ^{[1
]}

机构：

[1] Spanish Natl Canc Ctr CNIO, Telomeres & Telomerase Grp, Madrid 28029, Spain

[2] Spanish Natl Canc Ctr CNIO, Tumor Suppress Grp, Mol Oncol Program, Madrid 28029, Spain

[3] Univ Valencia, Dept Physiol, Valencia 46010, Spain

[4] Univ Complutense Madrid, Dept Anim Surg & Med, E-28040 Madrid, Spain

来源：

CELL | 2008年 / 135卷 / 04期

关键词：

D O I：

10.1016/j.cell.2008.09.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Telomerase confers limitless proliferative potential to most human cells through its ability to elongate telomeres, the natural ends of chromosomes, which otherwise would undergo progressive attrition and eventually compromise cell viability. However, the role of telomerase in organismal aging has remained unaddressed, in part because of the cancer-promoting activity of telomerase. To circumvent this problem, we have constitutively expressed telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice engineered to be cancer resistant by means of enhanced expression of the tumor suppressors p53, p16, and p19ARF. In this context, TERT over-expression improves the fitness of epithelial barriers, particularly the skin and the intestine, and produces a systemic delay in aging accompanied by extension of the median life span. These results demonstrate that constitutive expression of Tert provides antiaging activity in the context of a mammalian organism.

引用

页码：609 / 622

页数：14

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