Fruit fly research

Doug Skrecky (oberon@vcn.bc.ca)
Tue, 2 Jun 1998 09:31:13 -0700 (PDT)


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Extending health span with genetics

Fruit fly find suggests approaches for keeping youthful vigor

By Charlene Laino
MSNBC

June 1 Canadian scientists reported Monday that they have
successfully extended the life span of the fruit fly by inserting
into its DNA a designer gene that prevented some of the cellular
damage normally associated with aging. The approach holds potential
for increasing humans health span our days of youthful vigor, said
researcher John Phillips of the University of Guelph.

USING GENETIC ENGINEERING techniques, an extra gene was inserted
into the fruit flys motor neurons nerve cells that control
movement boosting their ability to remove toxins from the body and
extending their life span by 40 percent.

While an extra 30 days added to the normal 80-day life span
of a fruit fly might sound insignificant, the find has enormous
implications for biology, Phillips said.

We have discovered that [weakening of the detoxifying mechanism] in
motor neurons is the Achilles heel of life span, the Canadian
scientist said.

Drug companies are already working on new pharmaceuticals targeted
at the motor neurons that would work to increase our health span,
he noted. But perhaps even more importantly, the findings mark the
first time researchers have shown that a single gene in a single
type of cell can affect longevity.

We were really surprised, said study head Gabrielle Boulianne, a
neurobiologist at the Hospital for Sick Children and a professor of
molecular and medical genetics at the University of Toronto. We now
know that just manipulating just one gene, targeting one type of
cell, has a huge impact on aging.

Contrary to what was previously thought that many different
factors contribute to aging it now appears that the process may be
simpler, Boulianne said. The study is published in the June issue
of the journal Nature Genetics.

The new research grew out of work showing that the efficiency with
which organisms use oxygen directly correlates to their life span,
Phillips said. Humans, who have the longest lives of any organism,
are the most efficient users of oxygen, for example, while mice and
hummingbirds, who have relatively short lives, are inefficient
users.

The reason, he said, is that oxygen is very toxic. Even at the 21
percent atmospheric oxygen that we breathe, there has evolved a
detoxifying mechanism without which we would all keel over and die,
Phillips explained.

Over the past decade, scientists have identified the genes
responsible for this detoxifying mechanism. When this gene is made
inactive via a human-made mutation in the fruit fly, Phillips said,
its life span is reduced by some 80 percent to 90 percent.

At about the same time, researchers came to better understand that
motor neurons are somehow associated with this detoxifying
mechanism. Studies have shown that people with Lou Gehrigs disease,
a paralytic disorder that is caused by a loss of motor neurons,
tend to have family members whose genes controlling oxygen
detoxification are faulty, for example.

Moreover, in species ranging fruit flies to humans, there is
evidence that loss of motor neuron function is a prominent feature
of disease, aging and death, molecular biologist Phillips said. We
theorized that motor neurons might be at the nexus of aging and
oxygen metabolism.

That research led to the question: What would happen if we
upgraded that detoxification defense mechanism? Would the organism
live longer?

To answer the question, the team created a designer gene that
would enhance oxygen detoxification in motor neurons. The
human-made gene was then added to the fruit flys normal genetic
makeup. The experiment worked. Not only did the gene help the motor
neurons eliminate more waste, but the fruit flies they lived
longer.

Drug companies are already working on new antioxidant formulas
targeted at the motor neurons that work more efficiently in the
nervous system to rid our bodies of toxins and increase our health
span, Phillips said.

While some theorize that the approach could be used to create a
pill that would let us all live 40 percent longer boosting average
age from 80 to 110 Phillips said that is not his intention. There
are too many social implications, he said. Already there are
problems with old-age pensions, for example.

Rather, the find can be used to help us live healthier, avoiding
the sickness and disease normally associated with old age, he said.
The way in which the approach extended the life span of the fruit
fly is encouraging, Phillips said. Life span was extended though
postponement of the onset of senescence. In other words, he said,
we could live our final days not in a geriatric ward, but full of
youthful energy.