Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice

Abstract

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.

Protective effects of ginsenoside Rg1 on aging Sca-1+ hematopoietic cells

“…The results also revealed prolonged telomere lengths of the Sca-1 + cells following Rg1 treatment. The results of the present study also demonstrated that high levels of telomerase activities were responsible for stem cell telomere maintenance, which was consistent with a previous report that telomere maintenance is the predominant mechanism underlying the anti-aging phenotype of telomerase-overexpressing transgenic mice (26).…”

Telomerase deficiency and telomere dysfunction inhibit mammary tumors induced by polyomavirus middle T oncogene

“…Mice with transgenic Tert expression under the control of b-actin promoter also had increased incidence of spontaneous mammary tumors as they age . Coexpression of tumor suppressors p53, p16 and p19ARF in transgenic mice improved the fitness of epithelial barriers while attenuating the cancer-promoting effect of Tert (Tomas-Loba et al, 2008). Interestingly, tumor progression and dissemination by the constitutive expression of Tert was not dependent on telomere maintenance by telomerase as shown in Lck-Tert transgenic mice (Canela et al, 2004), suggesting that Tert per se may have a role in tumor progression and dissemination.…”

The mechanism of ageing: primary role of transposable elements in genome disintegration

“…The activity of the telomerase enzyme complex responsible for maintaining the structure of the chromosome ends (telomeres) at each round of cell division likewise affects lifespan in a number of model organisms [11,12]. Still, the ageing process of postmitotic cells (like neurons) contradicts the theory.…”