Eternal youth?

A newly-discovered enzyme may hold the key to longevity.

On April 15th 2005, as part of annual world-wide day in science, I (writer) was lucky enough to spend a day with some researchers who are trying to determine whether a newly-discovered enzyme is the key factor in aging, and whether or not giving an organism more of it could slow down the aging process. Two years ago, pharmacology researchers Vimal kapoor, then at the University of New South Wales in Sydney, Australia, was inspired by an article describing a newly discovered enzyme.The researchers has identified this enzyme as Pre-B-cell colony Enhancing Factor or PBEF but were not sure of its exact role. The journal article was not widely distributed or cited but the results caught Kapoor's attention: he had a theory that this new enzyme might actually be missing link in the chemical pathway that causes aging.

Forever Young??

When we witness the signs of aging, it's because a large amounts of cells in the body have reached the end of their useful lives and essentially disassemble themselves through a process called apoptosis. Cell death in areas like heart, lungs, immune system, muscles, and nerve tissue occur in old people and can makes them physically weaker and prone to illness. When cells are young and healthy, a chemical called NAD helps provide cells with energy so that they can create new chemicals, and it is thought that PBEF, which is present in all of our cells, may play a significant role in the recycling of NAD. Supplying our cells with more PBEF could therefore be like giving them a new dose of energy: it could reduce the rate of programmed cell death and thus slow down the aging process.

Research into the role of PBEF has also linked it to a range of chemical mechanisms that regulate cell growth. Interestingly, some cancer cells express PBEF in larger quantities and may be part of the reason that they multiply so quickly. "Cancer cells live forever,"says Kapoor,"and PBEF could be the key."

Kapoor and his research team, which included neuroscience hoors student Piroska Bisits Bullen, set out to further investigate the furthur role of the enzyme. Their first challenge was to isolate PBEF and determine its DNA sequence. To do this, they had to modify E.coli bacteria to produce the enzyme artifically and then develop a process for purifying the result so that they could isolate the enzyme. According to Bisits Bullen, this step was the trikiest. "E.coli is very temperamental. Working out exactly the right growing conditions to make them produce the enzyme in the right way took over a year."

When I visited the lab, Bisits Bullen had sucessfully found numerous ways of producing the enzyme and after long hours of trail and error, the researchers had produced large quantities of the pure enzyme. Work was underway to test the effect of the enzyme on individual cells to see if it could really influnce the rate of aging of organisms.

One year later, Kapoor and his research team have sucessfully produced crystals of the enzyme and are trying to determine its 3D structure using a technique called x-ray crystallography. "We will soon know what this enzyme looks like down to one or two Angstroms."says Kapoor. "From this , we hope to be able to develop novel anti-cancer drugs that can block it and thus slow down the multiplication of cancer cells."

But they are still the long way off from extending our life span, which Bisit Bullen says poses many ethical issues. For example , at present the only way to deliver PBEF to all the cells in human body would be to genetically modify the person's egg cell before it grows into the fetus, ensuring that the body's cell chemistry is altered from the moment that the person is concieved. It may be possible to develop the different ways of delivering PBEF to cells, but this is still amajor hurdle to overcome, and may take adecade or more.

Eternal youth ? Perhaps one day, but it seems that PBEF may initially be destined to prolong the lives of those who needed it most.


From Science Monitor