Tomás-Loba Antonia, Flores Ignacio, Fernández-Marcos Pablo J, Cayuela María L, Maraver Antonio, Tejera Agueda, Borrás Consuelo, Matheu Ander, Klatt Peter, Flores Juana M, Viña José, Serrano Manuel, Blasco Maria A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain.
Cell. 2008 Nov 14;135(4):609-22. doi: 10.1016/j.cell.2008.09.034.
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.
端粒酶通过其延长端粒的能力赋予大多数人类细胞无限增殖潜能，端粒是染色体的天然末端，否则会逐渐磨损并最终危及细胞活力。然而，端粒酶在机体衰老中的作用仍未得到解决，部分原因是端粒酶具有促癌活性。为了解决这个问题，我们在通过增强肿瘤抑制因子p53、p16和p19ARF的表达而设计的抗癌症小鼠中，组成型表达端粒酶逆转录酶（TERT），它是端粒酶的组成成分之一。在此背景下，TERT的过表达提高了上皮屏障的健康状态，尤其是皮肤和肠道，并产生了全身性的衰老延迟，同时伴随着平均寿命的延长。这些结果表明，在哺乳动物机体中，Tert的组成型表达具有抗衰老活性。
