Enzyme takes us a step closer to eternal youth (New Scientist)

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Enzyme takes us a step closer to eternal youth

* 19 November 2008 by Geddes

COULD artificially raising levels of a key enzyme hold back the

effects of ageing? It has long been a hope but now two lab experiments

- one with human cells and one in animals - are providing the first

evidence that this may actually be possible.

The

enzyme in question is telomerase, which is present naturally in some

mammalian cells. Its function is to maintain the protective caps called

telomeres at the ends of our chromosomes, which unravel with each cell division

as we get older. It has been suggested that this shortening triggers

some of the negative effects of ageing at a cellular level. As a

result, telomerase has been hailed by some as a potential elixir of life.

One

of the latest studies confirms that at least one type of human cell can

indeed be restored to a youthful state by boosting telomerase levels.

The other suggests that boosting telomerase can result in longer life

in animals. While an elixir of life in people remains a very long way

off, the prospect of boosting telomerase to fight disease, including

age-related diseases, may be much closer.

With the aim of fighting HIV, immunologist Rita Effros at the University of

California, Los Angeles, previously inserted part

of the telomerase gene into immune cells called killer T-cells. While

this did indeed boost their ability to fight viral infections, such

gene therapy is considered too dangerous to be used in practice.

So in her latest experiments, Effros has turned to a drug called TAT2, developed

by Geron of Menlo Park, California, that boosts telomerase production without

altering anyone's DNA.. When killer T-cells from people with HIV were

exposed to TAT2, it enhanced the cells' ability to fight the virus,

suggesting that TAT2 might be used to supplement existing

anti-retroviral drugs by boosting the immune systems of people with HIV

(The Journal of Immunology, vol 181, p 7400).

This

idea is supported by a previous study which indicated that some people

with HIV who go for years without developing AIDS have killer T-cells

with high telomerase activity and longer telomeres. Since T-cells fight

many viruses, TAT2 might eventually be deployed to boost resistance to

a whole range of diseases.

TAT2

also increased the cells' ability to divide and stopped their telomeres

from shortening, which raises the possibility that it might be used to

wind back the clock of other ageing cells and provide more general

treatments for ageing.

Aubrey de Grey of the Virginia-based Methuselah Foundation,

which promotes research into extending lifespan, certainly sees the

study as a big step in that direction. " It is what we would have

hoped, " he says. He is particularly interested in the fact that the

cells seemed to be " fully functional " in their new role as youthful

immune cells, raising hopes that telomerase might wind back the

cellular clock more generally.

Some safety concerns remain, however, not least because cancer cells produce

telomerase at higher than normal rates.

" With anything that boosts telomerase, you may have unwanted cell

growth like in cancers, " says Arne Akbar, an immunologist at University

College London.

However,

when TAT2 was added to tumour cells it did not affect the amount of

telomerase they produced. Nor did it change the growth characteristics

of immune cells that were cultured with a virus that can trigger

cancer. " We are fairly confident at this point that TAT2 won't enhance

cancer development, " says Effros, although further trials are needed to

confirm this.

Telomerase is extracted from the Astragalus plant, which is used in Chinese

medicine without any obvious adverse

effects. While this may help pave the way to pilot studies in humans in

the near future, Effros warns against taking large doses of Astragalus to try

and mimic the TAT2 effect. " Uncontrolled use of any herbal drug is not wise and

I would not advocate it, " she says.

Even

if telomerase proves successful at holding back some of the effects of

ageing at a cellular level, it is still a big jump from there to

something that stops a person as a whole from ageing. Yet this prospect

too has been brought a step closer with an announcement last week from

Blasco at the Spanish National Cancer Centre in Madrid and her

colleagues.

Telomerase

has previously been shown capable of turning " a normal, mortal cell

into an immortal cell " , as Blasco puts it. But whether this translates

into delaying ageing in live mammals has previously been difficult to

test, as high levels of telomerase tend to promote cancer, which

shortens their lives.

So

Blasco's team bred mice engineered to be resistant to cancer with mice

engineered to produce 10 times the normal levels of telomerase in

epithelial tissue, which lines the cavities and surfaces of the body.

These animals lived up to 50 per cent longer than normal mice (Cell, DOI:

10.1016/j.cell.2008..09.034). " You can delay the ageing of mice and increase

their lifespan, " says Blasco.

Blasco's

mice also had less subcutaneous fat, healthier epithelial tissue and

improved neuromuscular coordination and glucose tolerance, which are

all signs of youth. Boosting telomerase also seemed to have beneficial

effects on the animals' brains and muscles, even though the enzyme was

not expressed in these tissues.

Effros

warns against concluding that this means we can prevent ageing in

humans. " I think it is very hard to extrapolate data from mouse ageing

to human ageing, " she says. In particular, she points out that all mice

have longer telomeres than humans, and the lab mice are bred in sterile

conditions.

Blasco,

however, is optimistic that a similar approach may eventually extend

human lifespans. She suggests that the treatment could be combined with

cancer drugs to offset any enhanced cancer risk.

" We're

learning to control cell division in a manner that gets the best of

both worlds, " says de Grey, " allowing it to happen when we need it, and

not to happen when we don't. "

We're getting the best of both worlds - allowing cell division to happen when we

need it but not to happen when we don't

http://aging-management.com/ - Optimising Health for Longevity