Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice
Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice
复制标题
DOI：
10.1038/sj.onc.1208413
复制
发表时间：
2005-03-24
期刊：
影响因子：
8
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
González-Suárez, E;Geserick, C;Blasco, MA
许多随年龄增长而发生的退行性疾病，以及早衰综合征，其特征是呈现端粒极短的细胞。端粒酶再引入被设想为以端粒衰竭为特征的疾病的假定治疗方法。K5-mTert转基因小鼠在广泛的组织中过表达端粒酶。这些小鼠有更高的诱发和自发肿瘤的发生率，导致死亡率增加。生命的第一年。在这里，我们表明，尽管肿瘤发病率升高，最初的存活率较低，但K5-mTert小鼠显示出最长寿命从1.5个月延长到3个月，这取决于转基因系，与野生型幼崽相比，平均寿命增加了10%。这种较长的寿命与某些与年龄相关的退行性疾病（主要是与肾功能和生殖系完整性相关的疾病）的发病率较低相吻合。重要的是，端粒酶过表达的这些影响不能归因于老年K5-mTert小鼠端粒长度与野生型小鼠相比的巨大差异，正如定量端粒FISH所显示的那样。这些。研究结果表明，端粒酶过表达延长了小鼠的最大寿命。
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-mTert mice compared to wild-type mice, as shown by quantitative telomeric FISH. These. findings indicate that telomerase overexpression extends the maximum lifespan of mice.