Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice.
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.
González-Suárez
Eva
E
Molecular Oncology Program, Spanish National Cancer Centre, E-28029 Madrid, Spain.
Geserick
Christoph
C
Flores
Juana M
JM
Blasco
María A
MA
D000375:Aging / Q000502:physiology*; D000818:Animals; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D006965:Hyperplasia; D006984:Hypertrophy; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008136:Longevity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000201:enzymology / Q000473:pathology; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse