constant overexpression of telomerase portal 05-14-2015d1443

2015-05-17

constant overexpression of telomerase portal 05-14-2015d1443
constitutive overexpression of telomerase

some notes 


"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."






-q: More recently, Maria Blasco and her team could show that mice constitutively overexpressing Tert in thymocytes and peripheral T cells (Lck-Tert mice) had a higher incidence of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls


-q: They have generated two mouse models that over-express Tert under the keratin-5 promoter (K5-Tert) and the Lck promoter (Lck-Tert), thus targeting Tert expression to stratified epithelia or thymocytes, respectively.

TERT overexpression appears to play a protective role in murine disease and
ageing. Enforced overexpression of mTERT in stratified epithelia (K5-mTERT)
increased telomerase activity (Gonzalez-Suarez et aI., 200 I) and delayed telomere
loss with age (Tomas-Loba et aI., 2008). KS-mTERT mice possess a lower incidence
of age-related degenerative diseases, but a higher incidence of both induced and
spontaneous tumors (Gonzalez-Suarez et aI., 200 I , 200S). To overcome the potential
cancer-prone consequences of TERT overexpression, KS-mTERT was introduced
into a genetic background in which the tumor suppressors p53, p16, and p19ARF were
overexpressed. The resultant offspring exhibited improved fitness and an increased
median lifespan (Tomas-Loba et aI., 2008).
"