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R&D on Ageing: the biomedical viewpoint

Interview with MARíA A. BLASCO

Deputy Director of the Centro Nacional de Investigaciones Oncológicas (CNIO) and director of the Telomeres and Telomerase group

«Human beings born with shorter telomeres due to telomerase mutations live shorter lives»

In this interview Maria A. Blasco describes some of the findings of her research work

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Telomeres and telomerase are the focus of the research done by Maria A. Blasco and her team at the Centro Nacional de Investigaciones Oncológicas (CNIO). Can you explain what they mean in layman’s terms?
Telomeres form the tip of the chromosome and are essential in protecting them from degradation during fusion and recombination. They have been likened to the plastic at the end of a shoelace to stop it HIGHLIGHTSProfile: Maria A. Blasco
fraying. Telomeres are made of repeated DNA sequences (hundreds of repetitions of the sequence TTAGGG).

These sequences are unique in the genome and serve as an anchoring point for a group of specific telomere proteins called shelterins, whose role is to protect the telomere. Telomeric DNA repetitions are shortened with each cell division, which means that eventually the shelterins cannot attach to the chromosomes and protect them. This process is correlated with organismal ageing and has been shown to cause it.

It would not be possible to pass our genes down the generations or indeed for the continued existence of our species without telomerase, which is an enzyme able to extend the telomeres de novo in early stages of embryonic development. Telomerase is silenced in many adult tissues after completing its embryonic function, which results in the telomeres shortening with age.

María A. Blasco   María A. Blasco. /
Photo: CNIO

Telomerase plays two roles. On the one hand it is involved in the process of cellular ageing, where it is linked to the organism’s physiological ageing, and on the other it is associated with the appearance of tumour cells. How is this ambivalence possible?

It isn’t really an ambivalence. The absence of telomerase causes ageing, so tumour cells need to reactivate telomerase in order to escape from ageing or cellular senescence. Over 95% of human tumour types activate telomerase in order to be able to divide indefinitely.

Is it possible to quantify the genetic lifespan of an individual human being from telomere length?
Human beings born with shorter telomeres due to mutations in their telomerase live shorter lives. This normally occurs as a result of a premature loss of the tissue-regenerative capacity. Moreover, telomere length is a predictor of mortality from
“The absence of telomerase causes ageing”cardiovascular and infectious disease, which are the most frequent age-related causes of death.

Is it currently possible to modify an organism’s longevity by altering its genes?
This has already been done in a whole range of organisms from C. elegans to mice. It has not yet been attempted in humans but that may change when gene therapy recovers momentum. Gene therapy would make it possible to introduce genes in a chosen organ at the right momento to cure or prevent diseases associated with ageing.

Has telomerase been applied in drug form in anti-ageing treatments?
A telomerase activator is being used as a nutritional supplement in humans. The compound is a purified plant-extract. Drugs that are more powerful telomerase activators are still under development.

Imagen de cromosomas mostrando los telómeros

Image of chromosomes with the telomeres highlighted. / Photo: CNIO

Your work suggests that there is a correlation between the length of the telomeres, which are much shorter in the absence of telomerase, and the appearance of haematological, intestinal and above all neuronal disorders. What is behind this?
The absence of telomerase leads to a progressive shortening of the telomeres. Critically shortened telomeres mean the stem cells lose the ability to regenerate tissues, which leads to degenerative pathologies.

“In culture, telomerase immortalises most human cell types”Your work suggests that turning telomerase on and off would allow us to manipulate cellular ageing and the pathologies associated with this process. How?
Activating telomerase would allow us to rejuvenate the telomeres and thus enhance the proliferative capacity of the tissues and so delay their ageing.

What stage has been reached by research into the development of potential drugs to inhibit telomerase and avoid the development of cancer?
Telomerase inhibitors are being used in phase I-II trials with cancer patients. So far they have shown themselves to be relatively non-toxic and the trials are continuing.

The telomere and telomerase research group at the Centro Nacional de Investigaciones Oncológicas. From left to right: (seated) Rosa María Marion, Gerdine Stout, Paula Martinez; (standing) Águeda Tejera, Raquel Blanco, Carolyn McNees, Fabian Jordi, Irene Siegl, Ralph Schneider, Rosa María Serrano, Antonia Tomás and Elsa Vera. / Photo: CNIO

Would it be possible to immortalise any type of cells with telomerase?What benefits might this have for human beings?
In culture, telomerase immortalises the majority of human cell types. In experiments using mice as the model organism we have seen that increasing telomerase means they live 40% longer than normal.

Could ageing be the result of a shortage of stem cells?
Ageing affects most of the organism’s cells and systems, probably including stem cells Understanding the mechanisms by which stem cells age is one of the major topics of interest today.

Profile: Maria A. Blasco

(Alicante, 1965). She received her Doctorate in Biochemistry and Molecular Biology in 1993 from the Madrid Autonomous University, where her thesis was supervised by Margarita Salas Falgueras. That same year she started working as a postdoctoral researcher at Carol Greider’s laboratory in Cold Spring Harbor Laboratory, NY, USA. In 1997, she took up a post as a CSIC scientist and head of a research group in the Immunology and Oncology Department of the Centro Nacional de Biotecnología (CNB).

She has been with the Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre, CNIO) since its creation and is currently director of the CNIO Telomere and Telomerase Group and deputy director of the institution.

Among other accolades, Maria A. Blasco has been awarded the Santiago Ramón y Cajal Prize for Biology, the King Jaime I Prize for Basic Research and the Josef Steiner Cancer Research Prize.

Published in No. 02

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  • Lychnos. ISSN: 2171-6463 (Spanish print edition),
    2172-0207 (English print edition), 2174-5102 (online edition)
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