From: Gina Miller (echoz@hotmail.com)
Date: Sat May 15 1999 - 00:30:23 MDT
Date: Posted 5/14/99
Enzyme Required To Prolong Life In Worms Identified By Researchers At
Columbia; Key Enzyme Appears To Protect Animal Cells From Oxidative Damage
Researchers at Columbia University have discovered an enzyme that is
required to prolong the life span of microscopic roundworms and that strains
of long-lived worms appear to produce in greater quantity than normal.
They believe the enzyme, called cytosolic catalase, protects cells from
oxidative damage, considered a key element in the aging process in all
animals, including humans. Because oxidative damage has been implicated in
Alzheimer's and Lou Gehrig's disease, the work may prompt medical
researchers to ask new questions about such nervous system diseases.
"Our work demonstrates that oxidative damage is an important determinant of
life span, and control of such damage might affect the life span of other
organisms," said Martin Chalfie, professor of biological sciences at
Columbia and leader of the team that produced the research, which is
described in the May 13 issue of the British journal Nature.
The research was carried out in Caenorhabditis elegans, a soil worm about
1/25 of an inch long that is a common experimental animal. The tiny worm has
been useful to aging research because its normal three-week life span can be
extended by environmental factors. In situations of overcrowding, food
shortages or both, the emerging worm goes into a dormant period that can
last as long as two months. If food is provided within that time, the animal
emerges from dormancy and goes on to live its normal three weeks.
Scientists studying a possible genetic component to life span have been
fascinated by this extended larval phase, called the dauer stage. "Dauer"
means "lasting" in German. Several scientific teams have found mutations
that send the worm into the dauer state at elevated temperatures. But even
at normal temperatures and without going into the dauer stage, these mutant
adults live two to four times longer than non-mutants. Yet these same
mutants, if also bred to lack cytosolic catalase, died after three weeks,
the Columbia researchers report.
"Scientists in the past have found mutations in C. elegans that affect the
development of dauer larva and also prolong adult life," Professor Chalfie
said. "However, until this paper it was not clear how that was accomplished.
We believe we have found a key component."
That key component is cytosolic catalase, a protein that is also called
CTL-1, which protects cells in the long-lived mutant worms from oxidative
damage, thereby keeping them healthy. Mutant adult worms with long life
spans exhibited elevated levels of the enzyme, as did non-mutants in the
dauer stage, the Columbia team reports, but cells in normal adults do not.
"Our explanation for the long life spans in the mutant worms is that the
catalase is protecting the cells from oxidative damage and keeping them
healthy," Professor Chalfie said.
Oxidative damage occurs when oxygen-based compounds react with components of
cells, modifying them and in some cases making them harmful to the cell.
Such oxygen species -- peroxides, hydroxides and superoxides -- can be
produced both in chemical reactions in the cell and from reactions between
oxygen and ultraviolet light, a component of sunlight. Anti-oxidants such as
vitamin E are thought to provide some protection against these molecules.
Some chemical reactions in cells produce hydrogen peroxide, but those
reactions are confined to subcellular compartments, called peroxisomes, that
contain catalases to rid the cell of this harmful product. Until the
Columbia paper, animal cells were thought to have only peroxisomal catalase,
though cytosolic catalase had been seen in both plants and yeast. The new
catalase just identified, the first such enzyme found in animals, resides in
the cell fluid, not within a specific compartment. In this more general
location, the cytosolic catalase could act as a kind of surveillance system,
removing harmful peroxides from throughout the cell. The research team
dubbed the catalase CTL-1, and named the gene that produces it ctl-l.
Because the cells in adult roundworms do not divide, the research may be
applicable to non-dividing cells in other animals, such as human nerve
cells. Damage from oxidative stress has been implicated in nervous system
diseases, including Alzheimer's disease and amyotrophic lateral sclerosis,
or Lou Gehrig's disease. Vitamin E is sometimes administered to combat
Alzheimer's.
Past work on the dauer larvae suggested that a series of genes might control
dauer formation and longevity. Professor Chalfie said there is as yet no
evidence for any particular gene that controls life span either in worms or
in humans, and that the Columbia research shows that cytosolic catalase
simply protects cells from oxidative damage. In this view, the key to longer
life spans would simply be to keep cells as healthy as possible by avoiding
such hazards, rather than by activating some component of the genome.
"Our work suggests that the catalase pathway does not control adult
longevity, but rather that when the pathway is disrupted, adults live
longer," Professor Chalfie said. "In worms, genes do control the dauers to
make them healthy, but there is no evidence so far that genes regulate life
span in adults. The catalase genes are needed to make healthy, long-lived
dauers, and in the mutants they are being inappropriately expressed to make
adults live longer."
How could animals have acquired a gene that would have allowed them to live
longer? An evolutionary argument can be made that acquiring a gene to extend
adult life after reproduction would be difficult, if not impossible,
Professor Chalfie said. However, a gene that would extend the dauer period,
a dormancy period before reproductive maturity, might convey a selective
advantage to the animal. Another explanation is that extended longevity in
worms is a part of a more general mechanism that is a response to
starvation, during which animals produce enzymes, such as cytosolic
catalase, that protect cells.
The research team that made the discovery included James Taub, a graduate
student, and Jonathan Rothblatt, a biologist, who had studied C. elegans
catalases at Dartmouth but left to join the Chalfie laboratory. Columbia
undergraduates Rafaz Hoque and Joe F. Lau contributed to the work, as did
postdoctoral fellows Jang Hee Hahn and Charles Ma.
The research was funded by the National Institutes of Health and by the
American Cancer Society. Some strains of roundworm were received from the
Caenorhabditis Genetics Center, which is funded by the NIH National Center
for Research Resources.
Note: This story has been adapted from a news release issued by Columbia
University for journalists and other members of the public. If you wish to
quote from any part of this story, please credit Columbia University as the
original source. You may also wish to include the following link in any
citation:
http://www.sciencedaily.com/releases/1999/05/990514071624.htm
Gina "Nanogirl" Miller
Nanotechnology Industries
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