Public release date: 14-May-2012 [ | E-mail | Share ]

Contact: Juan J. Gomez juanj.gomez@cnio.es 34-917-328-000-4060 Centro Nacional de Investigaciones Oncologicas (CNIO)

A number of studies have shown that it is possible to lengthen the average life of individuals of many species, including mammals, by acting on specific genes. To date, however, this has meant altering the animals' genes permanently from the embryonic stage an approach impracticable in humans. Researchers at the Spanish National Cancer Research Centre (CNIO), led by its director Mara Blasco, have proved that mouse lifespan can be extended by the application in adult life of a single treatment acting directly on the animal's genes. And they have done so using gene therapy, a strategy never before employed to combat ageing. The therapy has been found to be safe and effective in mice.

The results are published today in the journal EMBO Molecular Medicine. The CNIO team, in collaboration with Eduard Ayuso and Ftima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Autnoma de Barcelona (UAB), treated adult (one-year-old) and aged (two-year-old) mice, with the gene therapy delivering a "rejuvenating" effect in both cases, according to the authors.

Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. The therapy, furthermore, produced an appreciable improvement in the animals' health, delaying the onset of age-related diseases like osteoporosis and insulin resistance and achieving improved readings on ageing indicators like neuromuscular coordination.

The gene therapy utilised consisted of treating the animals with a DNA-modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in ageing. Telomerase repairs the extremes of chromosomes, known as telomeres, and in doing so slows the cell's and therefore the body's biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

This study "shows that it is possible to develop a telomerase-based anti-ageing gene therapy without increasing the incidence of cancer", the authors affirm. "Aged organisms accumulate damage in their DNA due to telomere shortening, [this study] finds that a gene therapy based on telomerase production can repair or delay this kind of damage", they add.

'Resetting' the biological clock

Telomeres are the caps that protect the end of chromosomes, but they cannot do so indefinitely: each time the cell divides the telomeres get shorter, until they are so short that they lose all functionality. The cell, as a result, stops dividing and ages or dies. Telomerase gets round this by preventing telomeres from shortening or even rebuilding them. What it does, in essence, is stop or reset the cell's biological clock.

But in most cells the telomerase gene is only active before birth; the cells of an adult organism, with few exceptions, have no telomerase. The exceptions in question are adult stem cells and cancer cells, which divide limitlessly and are therefore immortal in fact several studies have shown that telomerase expression is the key to the immortality of tumour cells.

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CNIO scientists successfully test the first gene therapy against aging-associated decline