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Aging News & Information
Naked Mole-Rat May Hold Answer to Longer Life but
Not Giving It Up, Yet
Researchers say they may change oxidative stress
theory of aging
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This 2002
photo by Cornell University shows 22-year-old
Dara Neuman, senior biology
major, looking at a naked mole-rat older than she was at the
time. See more below main story. |
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October 9, 2006 - Those of us most like the naked mole-rat may
outlive our contemporaries as does this friendly furless guy that lives
in the total darkness of underground burrows, yet holds the world
longevity record in the rodent kingdom. Why do they live so long?
Scientist have long studied that question without success, but a new
study says they show much higher levels of oxidative stress and damage
and less robust repair mechanisms than the short-lived mouse, findings
that could change the oxidative stress theory of aging, say the
scientists.
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Latest News |
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Naked Mole-Rat in News Again as Scientists find
Longevity Champs have Slower Metabolism
 These old rats studied for years still not
giving up secret of long life
October 10, 2006 - The world’s longest living rodent – the naked
mole-rat – is in the research news again today as scientists continue to
probe for the secret to its longevity. The latest study of the hairless
tunnel-dweller suggests that the thyroid may hold the answer to why they
live 10 times longer than most regular mice. They found that the naked
mole-rat has significantly lower levels of thyroid hormone, which speeds
metabolism, and hope this leads to the secret of aging.
Read more...
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Aging News & Information |
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The results fly in the face of the oxidative stress
theory of aging, which holds that damage caused by oxidative stress is a
significant contributor to the aging process.
The new study comparing the naked mole-rat, which
has a life span of 28 years, and the mouse, which has a lifespan of
three years, was presented yesterday at The American Physiological
Society conference, Comparative Physiology 2006: Integrating Diversity.
Under this theory, naked mole-rats should be better
at preventing or repairing oxidative stress than their much
shorter-lived cousin, the mouse.
The study, "High oxidative damage levels in the
longest-living rodent, the naked mole-rat," was done by Blazej Andziak
and Rochelle Buffenstein, of The City College of New York, Timothy P.
O'Connor, of Weill Medical College of Cornell University, and Asish P.
Chaudhiri and Holly Van Remmen of the University of Texas Health Science
Center, San Antonio.
Don't toss the oxidative stress theory of aging out
the window just yet, but prepare to modify it, said Buffenstein, the
senior author. Her team suspects that the naked mole-rat's longevity
stems from its ability to defend against acute bouts of oxidative
stress. That is, the kind of oxidation that happens because of an
unusual occurrence rather than the kind that happens as a result of
normal aerobic respiration.
For example, when hydrogen peroxide is added to a
culture containing naked mole-rat fibroblast cells, they remain viable
and appear to repair the acute damage more rapidly than shorter-lived
animals, explained Buffenstein.
What is old age?
We know that all organisms age and die. It's such
an inevitable course of events that most of us spend more time thinking
about how to hide the wrinkles and gray hair than we do about what our
cells are actually doing to usher us to the end. Physiologists are
looking at molecules and cells to understand this process.
One way to look at aging is to compare closely
related organisms with different life spans. That's why it made sense to
compare mole-rats and mice: They're the same size and they're rodents,
but the mole-rat lives to 28 years, about nine-times longer than the
mouse.
"Mole-rats must have something happening at the
biochemical level to allow them to do this," said Andziak, the study's
lead author. Specifically, he wanted to see if oxidative stress could
explain the difference.
Oxidative stress occurs during metabolism when
oxygen (O2) splits into single oxygen atoms, known as free radicals.
These oxygen atoms may circulate by themselves, or combine with other
atoms and molecules to form reactive oxygen species (ROS). ROS can
damage DNA, lipids and proteins thus impairing normal cellular function.
Antioxidants help to neutralize ROS, thus restricting the potential of
ROS to damage biological molecules.
Mole-rat has more oxidative stress
The study compared two-year-old naked mole-rats to
four-month-old mice. The researchers chose those ages so that the
animals would be equivalent ages relative to their maximum lifespans,
Andziak said.
First, the researchers compared the ratio of
reduced glutathione, an antioxidant, to oxidized glutathione. As the
body uses up its reduced glutathione to fight oxidative stress, the pool
of oxidized glutathione increases. This ratio of reduced to oxidized
glutathione is thus an indicator of oxidative stress: the greater the
ratio, the less oxidative stress has occurred. The oxidative stress
theory predicts that in naked mole-rats this ratio will be higher than
in mice.
When the researchers measured this ratio in the
liver, they found that the opposite was true. Mole-rats had less reduced
glutathione and thus a lower ratio, indicating the mole-rat experienced
much more oxidative stress. These results fit with the findings of a
previous study in which Andziak found that naked mole-rats did not have
superior antioxidant capacity when compared to mice. Mole-rats had much
lower activity of the ubiquitous antioxidant enzyme, cellular
glutathione peroxidase.
Mole-rat shows greater oxidative damage
The researchers next looked at how much damage the
oxidation had caused. It is possible, they reasoned, that the mole-rat
suffers greater oxidative stress, but its physiology had somehow
prevented damage from occurring.
The researchers measured oxidative damage in
lipids, DNA and proteins and found that naked mole-rats showed much
greater levels of damage to each of these biological molecules, in all
tissues assayed, when compared to mice. The study found multiple signs
of lipid damage: The level of isoprostanes found in the urine was 10
times higher in the naked mole-rat, the level of malondialdehyde in
liver tissue was twice as high and isoprostane levels in heart tissue
was two-and-a-half times the level of the mice.
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The Naked
Truth about Mole-Rats |
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Jill
Locantore wrote a feature story for the National Zoo in 2002
about naked mole-rats. These are some of the highlights.
● Naked mole-rats spend virtually their
entire lives in the total darkness of underground burrows.
● They are truly social. They live in
large colonies, presided over by a queen, in which only the
queen and a few select males breed while the rest of the
colony—all members of the same family—work together to raise
young and maintain the colony.
● Native Africans have long known of the
existence of the three-inch long naked mole-rats, which they
call sand puppies.
● Naked mole-rat colonies are organized
into strict hierarchical castes. At the top of the heap—second
only to the ruling matriarch—is the queen’s harem of one to
three males with whom she chooses to mate. Beneath these
high-status breeders are soldiers—both male and female—who
defend the colony against predators and foreign mole-rats.
● Queens may have as many as 900 puppies
in their lifetime and produce all the babies in the colony.
● The bossy queen rules her brood with
brute force, often venturing from her nest to check up on
subordinates.
● The queen gets particularly pushy when
she is close to breeding or when she senses that a non-breeder
is about to become reproductively active. The researchers
speculate that shoving may cause stress and inhibit hormone
release, which in turn prevents ovulation in females and leads
to lower testosterone and sperm count in males. Whatever the
mechanism, the vast majority of naked mole-rats are doomed to
a life of celibacy.
Photo by Jessie Cohen
Click to full story. |
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The researchers found significantly more protein
damage in the kidney and in the heart. DNA damage was greater in the
kidney and liver.
"All of the classical measures of oxidative stress
are higher in the mole-rat," Andziak concluded. "Given that naked
mole-rats live an order of magnitude longer than predicted based on
their body size, our findings strongly suggest that mechanisms other
than attenuated oxidative stress may explain the impressive longevity of
this species."
Next steps
The next step is to determine how the mole-rats
manage to live with the damage caused by oxidative stress. Buffenstein
said she suspects that the mole-rat is able to fend off the occasional
oxidative insult that can occur, and that may be more important than
what happens with the steady-state levels of oxidative stress that
result from normal metabolic activity.
Buffenstein theorizes that the naked mole-rats in
her laboratory suffer higher levels of oxidative stress than they would
in their natural underground habitat, where they encounter much lower
levels of oxygen. But this exposure at an early age may provide some
protection against acute oxidative stress and may be of considerable
importance in their resistance to bursts oxidative stressors throughout
their lives, she said.
"The naked mole-rat, with its surprisingly long
lifespan and remarkably delayed aging, seems like the perfect model to
provide answers about how we age and how to retard the aging process,"
Buffenstein said. "This animal may one day provide the clues to how we
can significantly extend life."
Editor's Notes:
The American Physiological Society was founded in
1887 to foster basic and applied bioscience. The Bethesda,
Maryland-based society has 10,500 members and publishes 14 peer-reviewed
journals containing almost 4,000 articles annually.
APS provides a wide range of research, educational
and career support and programming to further the contributions of
physiology to understanding the mechanisms of diseased and healthy
states. In 2004, APS received the Presidential Award for Excellence in
Science, Mathematics and Engineering Mentoring.
Mole-rat Methuselahs, at 26 years old
and counting, bolster evolutionary theory of aging, says
Cornell biologist
Nov. 6, 2002 - Virtually hairless,
venerably wrinkled and very nearly blind, naked mole-rats --
those homely rodents from underground Africa -- remind some
zoo-goers of little old men.
The resemblance is more than
coincidence. They really are really old males -- and
females, too -- biologists report in an article scheduled
for November publication in the Journal of Zoology
(Vol. 258, Part 3). Many naked mole-rats (Heterocephalus
glaber ) in laboratory colonies in the United States and
South Africa have lived more than 20 years, and some are at
least 26 years old, making them by far the oldest small
rodents in captivity.
That distinction won't get them
birthday greetings from the president. But their species is
being hailed as a perfect exemplar for the evolutionary
theory of senescence (or aging), which explains why some
bodies wear out before others. Senescence theory also tries
to explain, for example, why gerbils live only a couple of
years, humans regularly live eight to nine decades and
redwood trees for millennia.
"Whatever kind of organism it is, it's
going to senesce," says Paul Sherman, a professor of
neurobiology and behavior at Cornell University. "Of course,
good food and exercise, proper medical care and avoiding
risky behaviors may extend lives a bit. But nothing we can
do in our lifetimes or many more to come is likely to stop
senescence." Evolutionary biologists define the term as the
persistent decline in fitness components with age, due to
internal physiological deterioration.
In the paper, "Extraordinary life spans
of naked mole-rats," Paul Sherman, a professor of
neurobiology and behavior at Cornell University, and his
South African colleague Jennifer U.M. Jarvis report that
laboratory mole-rats have survived nearly three decades,
making their life spans about 10 times longer than other
similar-size rodents. "Life spans of naked mole-rats offer
strong support for evolutionary theories of aging," Sherman
notes.
Evolutionary biologists agree there are
two types of causes for the end of life. The proximate (or
immediate) cause, such as drowning or essential body parts
wearing out, gets reported in newspaper obituaries, whereas
the ultimate (or long-term) cause, the genetic explanation
for death, gets discussed in scholarly scientific papers,
and Sherman offers this explanation for the difference:
"Most people attribute aging solely to
wear-and-tear on individuals' bodies. We know about
oxidative damage to DNA and cells, so we tend to say things
like, 'He died because his heart failed.' True, that's the
proximate cause of death, but it doesn't explain why a
person's heart lasted much longer than a gerbil's heart.
Senescence theory does: Long before a particular man or
gerbil was born, natural selection had acted on the genomes
of their species to cause gerbils' bodies to senesce more
rapidly than humans' bodies.
"Proximate and ultimate explanations
for senescence are not alternative, they are complementary,"
Sherman adds. "The first identifies specific physiological
mechanisms whose breakdown results in senescence. The second
explains how natural selection has acted to maintain or fail
to maintain those mechanisms."
The Cornell researcher has studied
colonies of naked mole-rats living in transparent plastic
tunnel systems in his laboratory since 1979, first at the
University of California-Berkeley and then in Ithaca. Jarvis
has done the same for her mole-rats at the University of
Cape Town. The animal-care protocols they pioneered have
helped zookeepers worldwide to display the intriguing
creatures for the education of the general public.
While naked mole-rats are models that
support senescence (aging) theory, they are not perfect role
models for humans. Senescence occurs, simultaneously, on all
aspects of any organism, which means there is no single gene
for aging or for youth. "Senescence theory," says Sherman,
"tells us why the fountain of youth still eludes us -- and
probably always will." |
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