Telomerase reverse transcriptase delays aging in cancer-resistant mice.
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 overexpression 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.
Tomás-Loba
Antonia
A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain.
Flores
Ignacio
I
Fernández-Marcos
Pablo J
PJ
Cayuela
María L
ML
Maraver
Antonio
A
Tejera
Agueda
A
Borrás
Consuelo
C
Matheu
Ander
A
Klatt
Peter
P
Flores
Juana M
JM
Viña
José
J
Serrano
Manuel
M
Blasco
Maria A
MA
D000375:Aging; D000818:Animals; D002470:Cell Survival; D004817:Epidermis / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D019098:Telomerase / Q000378:metabolism*
D007334:Insulin-Like Growth Factor I; D019098:Telomerase