Worming Our Way to a Longer Life

A Canadian-led search hunt for immortality

Vancouver, BC, Canada | A Canadian-led research team has entered the hunt for immortality, reporting that it has uncovered a "treasure trove" of genetic ingredients with the potential to enhance longevity.

From studies of a small and simple worm, which genetically happens to have much in common with the sophisticated human, scientists from British Columbia, Missouri and Maryland say they have pinpointed genes linked to aging.

Among them is a gene that had never been described and appears to work like a master switch, protecting against the natural wear and tear of chromosomes that contain the genetic material inside each living cell.

"We think it's a major step forward in having an inventory of all the genes that may be candidates in slowing down the aging process," said Steven Jones, head of bioinformatics at the Genome Sequence Centre at the British Columbia Cancer Research Centre. "The suggestion of this work is that we have all the things needed for a longer life. Scientists can question the inevitability of aging."

With the greying of the baby-boomers and advances in genetics, researchers have come to see aging as a series of preventable diseases.

California Institute of Technology researchers reported in 1998 that they had doubled the life span of a fruit fly after disabling a single gene, nicknamed Methuselah for the biblical character who lived 969 years.

In December, University of Connecticut scientists reported they had found another gene that they dubbed Indy, for I'm Not Dead Yet, which also doubled the usual fruit-fly life span of 37 days.

Studies of aging in the fruit fly and worm are appealing to scientists because both creatures share common genes with people but have short enough life spans to be quick and convenient subjects.

The C. elegans worm in this study, for example, usually lives 15 days and versions of roughly half of its 20,000 genes are also found in the human genome (that contains an estimated 35,000 genes).

"You can go to long-living people in China [as researchers have done] but those types of studies can take years," said Dr. Jones, lead author of the report in the current issue of Genome Research.

Earlier insect studies, however, have pinpointed one age-related gene at a time. But in a display of 21st-century technological might, these scientists-cum-computer whizzes analyzing worm DNA have crunched reams of chemical code and found more than 2,000 genes in one go.

"From the technological standpoint, this is impressive," said Steve Scherer, senior scientist at Toronto's Hospital for Sick Children and associate director of its Centre for Applied Genomics. "This is the new era in genomics, a large-scale study of how genes work."

In the joint study, Vancouver scientists and collaborators at the University of Missouri, Johns Hopkins Oncology Centre in Baltimore and Washington University compared the life spans of a normal population of worms with a second population that had been induced into what is known as the "dauer state."

In the dauer state, a worm moves very little, eats very little and does not reproduce. The creature can metabolically flip itself into a dauer state under poor environmental conditions such as when there is not enough food to eat.

In the dauer state, Dr. Jones explained, a worm's life span can stretch from its average of two weeks to two months. This also jibes with the so-called Methuselah gene mutation in fruit flies, which can withstand external stresses such as food deprivation or excessive heat.

To analyze the genes that were switched into high gear during this state, the researchers froze the worms in the dauer state and then literally crushed them in liquid nitrogen with a mortar and pestle for five to 10 minutes. This way, scientists can separate the cells, siphon off their genetic material and, with the help of a computer, chemically read which genes have been "turned on."

The longer-living dauer worms were found to have 2,016 genes activated that were not triggered in the normal populations. Dr. Jones believes that a high proportion of these genes may hold clues to a longer life.

They included genes that trigger mechanisms for DNA to repair itself, those that produce antioxidants to protect cells against damaging free radicals and another that creates a unique coating around chromosomes.

But the gene that was found to be 20 times more active in the longer-living worms than the normal population was the newly discovered "tts-1." The scientists suspect it controls telomeres. Telomeres are like tails or caps on the end of chromosomes that keep genetic information intact but get shorter each time a cell divides. As cells age, telomeres wear down to an unstable nub and cells stop dividing, break down or die.

"This is exciting. This gene has never been identified and it seems to have a very interesting function," Dr. Scherer said. "People will be testing this out in other organisms and to see if it has a human equivalent."

Dr. Jones and his colleagues intend to activate the genes they have found in the normal worm to see if they can extend its life span. They will also be searching for the genes' human equivalents.