US Scientists Reverse Signs of Aging in Mice

Elderly mice restored to middle age

Jessica Berman | Washington, DC 01 December 2010

Harvard scientists say they were able to reverse signs of aging in mice by tweaking a gene which protects cells from the harmful, cumulative effects associated with growing old.

Scientists say they have reversed age-related degeneration in mice, resulting in an improvement in the rodents' fertility and the growth of new brain tissue. But it could be some time before the technique might be used in humans.

Fountain of youth

Scientists at Harvard University's Dana-Farber Cancer Institute in Boston report they were able to reverse signs of aging in mice by tweaking a gene that protects cells from the harmful, cumulative effects associated with growing old.

The gene is involved in the production of structures at the tips of DNA chromosomes called telomeres.

Telomeres are like the plastic caps on the ends of shoe laces that keep them from becoming frayed. In the case of chromosomes, the telomeres protect the strands of DNA from environmental assaults such as chemical and radiation exposure.

But every time a cell divides, its telemeres shorten, eventually leading to DNA damage and aging.

In studies with mice, researchers switched off the telomerase gene and watched the rodents rapidly develop age-related impairments.

Eternally young?

However, when they turned the genes back on on, the animals' declines reversed.

"Their fertility was restored. We also saw a big effect on the lining of the intestines and as well as in the brain, which was a little bit unexpected," says lead researcher Mariela Jaskelioff. "We actually saw a decrease in the size of the brains of these mice with premature aging. And we could reverse these by reactivating telomerase."

The mice in the study were at an age equivalent of an 80- or 90-year-old human. Researchers restored them to middle age by turning on the telomerase gene.

Despite the encouraging results, the genetic manipulation is not the secret to eternal youth for humans. Jaskelioff says the telomerase gene is involved in the growth of both normal and cancerous cells.

"The fear is that in humans, adult humans, we accumulate mutations all through our lifetimes," she says. "And if we were to reactivate telomerase in cells that have malignant mutations, then the propensity to develop cancer would probably be exacerbated."

However, according to Jaskelioff, it might be possible to stimulate the telomerase gene for short periods of time in people with a rare disorder which causes premature aging.

Scientists describe how they reversed aging in mice in an article published in the journal Nature Medicine.

Gene therapy 'memory boost hope'

This research adds a piece to the Alzheimer's puzzle and provides new leads for researchers”

Rebecca Wood

Alzheimer's Research Trust

A gene therapy technique which aims to ease memory problems linked to Alzheimer's Disease has been successfully tested in mice.

US scientists used it to increase levels of a chemical which helps brain cells signal to each other.

This signalling is hindered in Alzheimer's Disease, the journal Nature reported.

The Alzheimer's Research Trust said the study suggested a way to keep nerve cells in the brain communicating,

Ageing populations in many countries around the world mean that Alzheimer's disease and other forms of dementia are set to increase.

Researchers at the Gladstone Institute of Neurological Disease in San Francisco believe that boosting the brain chemical, a neurotransmitter called EphB2, could help reduce or even prevent some of the worst effects of the condition.

Their research suggests that the chemical plays an important role in memory, and is depleted in Alzheimer's patients.

One of the most noticeable features about the brains of Alzheimer's patients is the build-up of "plaques" of a toxic protein called amyloid. Over time this leads to the death of brain cells.

'Thrilled'

However, another characteristic of amyloid is its apparent ability to bind directly to EphB2, reducing the amount available to brain cells, which could in part explain the memory symptoms involved.

To test this idea, they used gene therapy experiments to artificially reduce and increase the amount of available EphB2 in the brains of mice.

When levels of the chemical were reduced, healthy mice developed memory symptoms similar to those seen in mice bred to have a condition similar to Alzheimer's.

Conversely, when the "Alzheimer's" mice were given gene therapy which boosted levels of EphB2, their memory symptoms disappeared.

Dr Lennart Mucke, who led the study, said that his team had been "thrilled" to find this.

"We think that blocking amyloid proteins from binding to EphB2, and enhancing EphB2 levels or functions with drugs might be of benefit in Alzheimer's Disease."

However UK researchers said that the find, while interesting, did not offer a swift answer to Alzheimer's patients.

Rebecca Wood, chief executive of the Alzheimer's Research Trust, said: "Our brains are hugely complex and understanding how they work and become damaged by diseases like Alzheimer's is a massive task.

"This research adds a piece to the Alzheimer's puzzle and provides new leads for researchers.

"It suggests a way to keep nerve cells in the brain communicating, which is vital for thinking and memory."

But she added: "We don't know yet if these findings will lead to a new treatment for Alzheimer's - that's some way off."

(BBC)