Gene therapy extends mouse lifespan by 24 pc

Washington, May 15 (ANI): Scientists have successfully extended the lifespan of mice using gene therapy, a strategy never before employed to combat ageing.

The therapy has been found to be safe and effective.

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 Maria 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.

The CNIO team, in collaboration with Eduard Ayuso and Fatima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Aut?noma 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 researchers.

Mice treated at the age of one lived longer by 24 percent on average, and those treated at the age of two, by 13 percent. 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The gene therapy utilised consisted of treating the animals with a DNA-modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in ageing.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 researchers said.

"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 added.

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.

It is precisely this risk of promoting tumour development that has set back the investigation of telomerase-based anti-ageing therapies.

In 2007, Blasco's group proved that it was feasible to prolong the lives of transgenic mice, whose genome had been permanently altered at the embryonic stage, by causing their cells to express telomerase and, also, extra copies of cancer-resistant genes. These animals live 40 percent longer than is normal and do not develop cancer.

The mice subjected to the gene therapy now under test are likewise free of cancer. Researchers believe this is because the therapy begins when the animals are adult so do not have time to accumulate sufficient number of aberrant divisions for tumours to appear.

Also important is the kind of virus employed to carry the telomerase gene to the cells. The researchers selected demonstrably safe viruses that have been successfully used in gene therapy treatment of haemophilia and eye disease. Specifically, they are non-replicating viruses derived from others that are non-pathogenic in humans.

This study is viewed primarily as "a proof-of-principle that telomerase gene therapy is a feasible and generally safe approach to improve healthspan and treat disorders associated with short telomeres", stated Virginia Boccardi (Second University of Naples) and Utz Herbig (New Jersey Medical School-University Hospital Cancer Centre).

Although this therapy may not find application as an anti-ageing treatment in humans, in the short term at least, it could open up a new treatment option for ailments linked with the presence in tissue of abnormally short telomeres, as in some cases of human pulmonary fibrosis.

The results of the new study are published today in the journal EMBO Molecular Medicine. (ANI)