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View Full Version : extra copy of a tumour-killing gene causes mice to live 25% longer


latent aaaack
19th July 2007, 10:50 PM
Well, PETA, it was the thought that counted.

Anyone know more about if this is the first suggestion that a cancer-supressor boosting drug could function as an anti-ageing treatment? I've heard about genetic or calorie intake modifications researchers have done to animals to increase their lifespan but not something that could be close to being done by pills in the foreseeable future.

http://www.nature.com/news/2007/070716/full/070716-8.html

excerpt:
Cancer-proof mice live longer

A protein known to keep cancer at bay now also looks to be a fountain of youth. Mice with an extra copy of the tumour-killing gene that pumps out this protein live longer than those with just one copy, and are better at combating the cell damage that causes ageing.

The finding hints that a drug designed to boost the tumour suppressor, called p53, could work as an anti-ageing treatment for people, says Manuel Serrano, a biologist at Spanish National Cancer Research Centre in Madrid. Serrano's team publish their work in this week's Nature1 (http://www.nature.com/news/2007/070716/full/070716-8.html#B1).

The conclusion seems to stand in direct contradiction to previous work2 (http://www.nature.com/news/2007/070716/full/070716-8.html#B2), which showed that a boost in p53 kept mice cancer free but also caused them to age more quickly. But there's a key difference between these studies, the researchers say: in the new work, the normal regulatory mechanisms remain in place, so p53 is churned out only when needed. This seems to turn an ageing protein into a youth-preserving one.

"It's a very impressive effect," says Larry Donehower of Baylor University in Houston, who led the older work. "It's very hopeful because it says under some circumstances you can get the best of both worlds."
....
But the age boost wasn't just an effect of fewer mice dying of cancer. When the researchers looked only at cancer-free mice in the study, they found that these transgenic mice lived 25% longer, on average, than normal ones. The oldest mice in both groups died at about the same age, but more of the transgenic mice lived into their golden years than the normal ones.

When the researchers looked more closely at the youthful mice, they found higher levels of genes that combat oxidative damage than in regular rodents. The mice with extra p53 also held up better against a lethal dose of paraquat, a drug that causes oxidative damage.

money
20th July 2007, 01:39 AM
What is oxidative damage?

Matt the Poet
20th July 2007, 03:16 AM
If I recall from my Uni biochemistry, it’s damage to biological molecules caused by Oxygen free radicals – electron-starved oxygen molecules that turn pretty quickly into damaging things like hydrogen peroxide, or nick electrons off other molecules (like DNA) to get stable

We’ve got a pretty good suite of enzymes for dealing with these, as they are unavoidable by-products of using oxygen to burn food for energy.

p53 is an interesting protein. It swings into action when damaged DNA is detected – binding to the damaged site and recruiting a whole complex of other enzymes which fix the problem. It’s not, strictly speaking, in the class of ‘tumour suppressor’ genes. Like the ‘breast cancer gene’ BRCA1 it acts as a ‘gateway’ to cancer development. Knock it out and you become globally more vulnerable to cancer because you accumulate DNA damage faster.

The problem with using these sorts of repair pathway genes therapeutically is that their function is so important, evolutionarily speaking, that they are heavily redundant – p53 is an important ‘checkpoint’ in the process but there are plenty of (admittedly less efficient) ways in which mutations get fixed without it

Hope that’s helpful…

money
20th July 2007, 09:59 AM
Hmm, very interesting. Thanks!

Beerina
20th July 2007, 12:32 PM
You also have to be careful extrapolating from something that lives 2-3 years to something that lives 80 years (natural biological average life, not counting accidents, etc.)

Like the "restricted calories" issue, did they add a 25% to a mouse's life? Or did they add four months to its life?

Extrapolating to humans, if it works, will you end up with an extra 20 years, or an extra four months?

latent aaaack
26th July 2007, 01:23 PM
Yet another anti-ageing advance:

http://www.nature.com/news/2007/070723/full/070723-10.html

Researchers have created a mutant mouse that lives longer despite eating more and weighing less — all thanks to the loss of a single protein.

Without this protein, the body is less susceptible to the heart-pounding effects of the hormone adrenaline, and may become more resistant to some forms of stress.

Scientists are already developing drugs to inhibit this protein, called type 5 adenylyl cyclase (AC5). "Clearly we would be very interested in such a compound," says cardiologist Stephen Vatner, who is part of the team that discovered this effect.

Currently, the main focus of ageing research is on using calorie restriction as a way of activating a metabolic 'fountain of youth'. The new discovery, that knocking out a single cardiac gene could lengthen lifespan, was an unexpected byproduct of heart research.

Vatner, together with Junichi Sadoshima and other colleagues at the New Jersey Medical School at the University of Medicine and Dentistry of New Jersey in Newark, had initially set out to determine whether getting rid of AC5 leads to a healthier heart.

Drugs that block adrenaline signalling, called beta-blockers, are known to help patients who have had heart attacks or suffer from an irregular heartbeat. As the researchers revealed in 2003, mutant mice lacking AC5 were more resistant to heart failure caused by pressure within the heart1 (http://www.nature.com/news/2007/070723/full/070723-10.html#B1).

But in the process, the research team also realised that the mutant mice lived longer than their normal counterparts. Now, in a paper published in Cell this week2 (http://www.nature.com/news/2007/070723/full/070723-10.html#B2), they report that the treated mice lived 30% longer and did not develop the heart stress and bone deterioration that often accompanies ageing.
....
Both Bristow and Hammond agree that the results are exciting and that they open up a new avenue of ageing research. But Hammond adds that although an AC5 inhibitor may make a fine drug for protecting the heart, there are more straightforward options for boosting longevity. "I think first what I would do is get people to slow down on the highway, stop eating Big Macs and stop smoking," says Hammond