Study: Rapamycin has harmful effects when telomeres are short

by The Spanish National Cancer Research Centre

(Source: Phys.Org News)

The study, done by the Telomeres and Telomerase Group headed by Maria Blasco at the CNIO, is published in Nature Communications with Iole Ferrara-Romeo as the first author.

But it also has clinical implications. Short telomeres are associated with, or are the cause of so-called telomere syndromes, diseases such as dyskeratosis congenita, aplastic anaemia, pulmonary and hepatic fibrosis, and other degenerative diseases for which few treatments exist. Blocking the mTOR pathway with rapamycin was considered a possible strategy against these diseases, but the results of the study suggest that it would not work, and could even be harmful.

"In light of all the beneficial effects of inhibition of the mTOR pathway in extending longevity, here, we set to address whether rapamycin treatment could also ameliorate the premature ageing phenotypes and the decreased lifespan of telomerase-deficient mice with short telomeres," the authors write. But, although "in control mice [with normal telomeres] rapamycin extended the lifespan, in mice with short telomeres it reduced it. We did not expect that. These results are of clinical interest for human diseases in which patients have critically short telomeres," explain Maria Blasco and Paula Martínez, authors of the paper.

Telomeres, regions of repetitive nucleotide sequences at the end of chromosomes, preserve the genetic information of the cells. They shorten with age until they can no longer fulfill their function: The cells stop dividing and the tissues age since they are no longer able to regenerate. 

"This discovery indicates that hyper-activation of the mTOR pathway is necessary to compensate for problems arising from having short telomeres," Blasco explains.