Document Detail


Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice.
MedLine Citation:
PMID:  15688016     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many degenerative diseases that occur with aging, as well as premature aging syndromes, are characterized by presenting cells with critically short telomeres. Telomerase reintroduction is envisioned as a putative therapy for diseases characterized by telomere exhaustion. K5-mTert transgenic mice overexpress telomerase in a wide spectrum of tissues. These mice have a higher incidence of both induced and spontaneous tumors, resulting in increased mortality during the first year of life. Here, we show that in spite of this elevated tumor incidence and the initial lower survival, K5-mTert mice show an extension of the maximum lifespan from 1.5 to 3 months, depending on the transgenic line, which represents up to a 10% increase in the mean lifespan compared to wild-type littermates. This longer lifespan is coincidental with a lower incidence of certain age-related degenerative diseases, mainly those related to kidney function and germline integrity. Importantly, these effects of telomerase overexpression cannot be attributed to dramatic differences in telomere length in aged K5-Tert mice compared to wild-type mice, as shown by quantitative telomeric FISH. These findings indicate that telomerase overexpression extends the maximum lifespan of mice.
Authors:
Eva González-Suárez; Christoph Geserick; Juana M Flores; María A Blasco
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  24     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-24     Completed Date:  2005-04-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  2256-70     Citation Subset:  IM    
Affiliation:
Molecular Oncology Program, Spanish National Cancer Centre, E-28029 Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Animals
DNA Primers
DNA-Binding Proteins
Female
Humans
Hyperplasia
Hypertrophy
Kidney / enzymology,  pathology
Longevity
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Polymerase Chain Reaction
RNA, Messenger / genetics
Skin / enzymology,  pathology
Telomerase / genetics*,  metabolism*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/DNA-Binding Proteins; 0/RNA, Messenger; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase; EC 2.7.7.49/Tert protein, mouse

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