2012 May 16 Wednesday
Telomerase Gene Therapy Boosts Mouse Longevity

Longer telomere caps on chromosomes enable cells to divide more times, replace lost cells, and do repairs. Lengthening the caps on telomeres increases life expectancy in mice.

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 María 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 Fátima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Autònoma 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.

This is an interesting result for a number of reasons. First off, why don't mice just have longer telomeres at the start? If the increased life expectancy has no cost in fitness why aren't mouse telomeres longer already?

Second, I am surprised that the longer telomeres didn't enable more cancer growth and therefore cause shorter life expectancy. Telomere shortening every time a cell divides acts like a counter on the max number of times a cell can divide. This functions as a defense against cancer. Some cancers mutate their way past this defense (e.g. by turning on telomerase to make telomeres longer). But presumably others get stopped by cells with telomeres too short to allow further cell division.

The researchers address the cancer issue in a way that suggests to me this would not work for humans.

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% 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.

Mice do not live that long to begin with. Humans at middle age given telomerase gene therapy would have decades in which to accumulate aberrant cells that can turn cancerous. So

Third, on the bright side the gene therapy was able to reach a large enough fraction of the cells in the bodies of mice to make a big difference. Very good news because we have need for lots of types of gene therapy to do rejuvenation of our bodies. I wonder what fraction of all the cells in the mice got the gene therapy.

As for the implications for humans: Keep in mind that we already live many times longer than mice. We've got an assortment of optimizations for longer life that might reduce the value of longer telomeres and our cancer risk from longer telomeres might be greater than for mice.

But even if telomere lengthening would boost our all cause mortality today that does not mean this must always be so. Once cancer becomes easily curable the risks from longer telomeres will go way down and we'll left with just the benefits. So gene therapy for telomere lengthening will likely become a useful technique for life extension in about 10 to 20 years.

We will gain another and safer way to get the benefits of longer telomeres: Cell therapy. Separate out cells. Then test different cell lines for mutations. Then extend the telomeres of the safest cells. Then grow up those cells in large numbers and inject those cells back into the body.

By Randall Parker    2012 May 16 07:16 PM   Entry Permalink | Comments (7)
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