The Curious Case of the Backwardly Aging Mouse

In F. Scott Fitzgerald’s short story, “The Curious Case of Benjamin Button,” an old man gets younger with each passing day, a fantastic concept recently brought to life on film by Brad Pitt. In a lab in Boston, a research team has used genetic engineering to accomplish something similarly curious, turning frail-looking mice into younger versions of themselves by stimulating the regeneration of certain tissues. The study helps explain why certain organs and tissues break down with age and, researchers say, offers hope that one day such age-related deterioration can be thwarted and even reversed.

As we age, many of our cells stop dividing. Our organs, no longer able to rejuvenate themselves, slowly fail. Scientists don’t fully understand what triggers this, but many researchers suspect the gradual shrinking of telomeres, the protective DNA caps on the end of chromosomes. A little bit of telomere is lost each time a cell divides, and telomerase, the enzyme that maintains caps, isn’t typically active in adult tissues. Another piece of evidence: People with longer telomeres tend to live longer, healthier lives, whereas those with shorter telomeres suffer more from age-related diseases, such as diabetes, Alzheimer’s, and heart disease.

Several years ago, Ronald DePinho, molecular biologist and director of the Belfer Institute of the Dana-Farber Cancer Institute, and colleagues at Harvard Medical School in Boston genetically engineered mice to lack a working copy of the telomerase gene. The animals died at about 6 months—that’s young for mice, which usually live until they are about 3 years old—and seemed to age prematurely. At an early age, their livers and spleens withered, their brains shrank, and they became infertile. By early adulthood, these mice exhibited many of the maladies seen in 80-year-old humans.

DePinho says he wondered what would happen to the aging process in these mice if they suddenly began making telomerase again. “Would [we] slow it, stabilize it, or would we reverse it?” He and his colleagues genetically engineered a new batch of mice with the same infirmity, but this time they added back a telomerase gene that became active only when the mice received a certain drug. The researchers kept the gene off during development and let these mice prematurely age, as the previous ones had. But then at 6 months, the team switched on the telomerase gene.

The burst of telomerase production spurred almost total recovery. The rodents became fertile, their livers and spleens increased in size, and new neurons appeared in their brains, the researchers reported online yesterday in Nature.

The ability to reverse age deterioration in the mutant mice indicates that the cells that divide to replenish tissues don’t simply die when their telomere clock expires, says DePinho. They apparently persist in a dormant state from which they can be revived. “One could imagine applying this approach to humans,” he says, focusing the therapy on specific tissue types such as the liver, where telomerase is thought to play an important role in regeneration after damage by hepatitis, parasitic infection, and alcoholism.

K. Lenhard Rudolph, who studies stem cell aging at the University of Ulm in Germany, says that the results are encouraging for people with diseases that cause accelerated aging, like progeria, because the mice in this study were rescued despite already suffering from the effects of chronic disease. “It is a proof of principle that telomeres are at work here.”

Drug companies and researchers are seeking ways to restore, protect, or extend a person’s telomeres, but the jury is still out on whether such interventions can slow the symptoms of aging, let alone reverse them. Telomere investigator Maria Blasco of the Spanish National Cancer Research Center in Madrid cautions that DePinho’s experiment shouldn’t raise people’s expectations of antiaging therapies just yet. “This study uses genetically modified mice,” she says. “What remains a very important question in the field is can you delay aging in a normal mouse?”

DePinho agrees with those concerns. He also warns that his approach has potential drawbacks, as increasing telomerase activity beyond its natural levels can cause cancer. Still, that may not be an insurmountable problem if telomerase levels can be carefully controlled. DePinho notes that the mice in his study, whose telomerase activity was returned to a natural level, didn’t develop tumors.

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London’s Natural History Museum Delays Expedition

London’s Natural History Museum (NHM) has suspended a month-long scientific expedition to a remote region of northern Paraguay in light of concern expressed by Paraguay’s government officials in a letter sent to museum officials. The letter mirrors fears raised last week by Iniciativa Amotocodie, a nongovernmental organization that represents indigenous peoples in Paraguay and has protested that scientists taking part in the expedition would run into the indigenous Ayoreo peoples who wish to have no contact with outsiders.

The expedition, which would have started this weekend, aims to explore an area called the Gran Chaco, a semiarid lowland sandwiched between the Andes and the Paraguay River that is a mecca for scientists interested in biodiversity. However, in a letter sent Friday to Richard Lane, scientific director of NHM, the director general of Paraguay’s Ministry of the Environment, Isabel Basualdo, asked for a suspension of the expedition until the concerns over contact with the Ayoreo peoples can be looked into. She writes: “The president of the Indigenous National Institute, whose responsibility it is to guarantee the rights of the indigenous population of Paraguay, warns that consent must be gained from the communities’ recognised leaders, who claim rights over the territory where such expedition will be made.” Basualdo goes on to say that in accordance with article 41 of the American Convention of Human Rights, a commission adopted in 1969 to protect the peoples of the Americas, the Paraguayan government has requested a cancellation of the expedition until such consent can be gained. But she also inidctates thet Paraguay is committed to the expedition and is working to resolve the problems as soon as possible.

The museum had been defending the expedition since the initial protest. (Here’s a video the museum posted of Lane discussing the matter). But in a statement yesterday, NHM said:

The Ministry for the Environment of Paraguay, one of our partners on the joint Natural History Museum and Paraguayan expedition to the Dry Chaco region, has decided to undertake further consultation with the Ayoreo people. The Natural History Museum supports this approach to ensure the community is properly informed and consulted. There will be a suspension of activities while this takes place. The concerns of the un-contacted people are extremely important to us. We will continue to take advice on these matters from the Paraguayan authorities. We hope that the issues can be resolved soon.

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Stroking reveals pleasure nerve

A new touch-sensitive nerve fibre responsible for the sense of pleasure experienced during stroking has been described at a UK conference today.

The nerves tap into a human’s reward pathways, and could help explain why we enjoy grooming and a good hug, a neuroscientist has explained.

His team used a stroking machine to reveal the optimal speed and pressure for the most enjoyable caress.

The research was presented at the British Association Science Festival.

Mothers stroke their children, monkeys groom group members, and we all enjoy a massage, but what is it about stroking and rubbing that we find so enjoyable?

“People groom because it feels good,” said Professor Francis McGlone, a cognitive neuroscientist at Unilever R&D, but went on to explain that little is known about how we experience the pleasure of touch.

In order to isolate the touch-sensitive nerves responsible for the pleasure experienced during stroking, Professor McGlone designed a “rotary tactile stimulator” – a high-tech stroking machine.

“We have built some very sophisticated equipment, so the stimulus [of stroking] is very repeatable.

“We stroke the skin [of the forearm, foreleg, and face] with a brush at different velocities, and then asked the volunteers to rate how they liked it,” he explained.

He also inserted microelectrodes through the skin, into a nerve, to record the neural signals running from the skin to the brain.

“It is like tapping a single phone-line and listening for the chatter that comes down that line,” he told the conference.

Feel-good chemicals

By comparing how the neural signals corresponded with how much the volunteers enjoyed the stroking, he was able to pin down people’s pleasure to one set of nerves called “C-fibres”.

He thinks that the stroking movements are activating C-fibres, which are wired into the rewards systems in the brain, causing the release of feel-good hormones.

Professor McGlone points out that these touch nerves are not responsible for the pleasure experienced from rubbing sexual organs, nor are they found in a person’s palms or soles.

“Experiencing pleasure when grappling with tools or walking, would make both task difficult to do with any accuracy,” he suggested.

The Liverpool-based researcher showed that stroking speeds of about 5cm per second, while applying 2g of pressure per square cm is optimal, and gave the volunteers most pleasure.

He explained that the pleasure messages are conveyed from the skin to the brain, by similar types of nerve fibres as those that transmit the sensation of pain.

“This is interesting as we often rub a pain to try to alleviate it,” he said.

This could explain why the pain experienced by people exposed to a painful thermal stimulus, lessens when the region of the stimulus is simultaneously stroked.

Stroking could be used to treat chronic pain, he suggests.

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Hungry seals ‘steer by the stars’

Seals can identify a single star in the night sky and navigate by it, scientists have discovered.

Navigating in the open ocean is essential for seals to move between foraging grounds that may be hundreds of kilometres apart.

This is the first evidence that marine mammals, like humans, use stars to navigate in open water, say scientists.

The European team has published details of its work in the journal Animal Cognition.

The researchers, headed by Dr Guido Dehnhardt of University of Rostock in Germany, simulated a night sky above two captive male seals and monitored the movements of the animals through six hidden infrared cameras.

“Initially, the seals were guided to one of the brighter stars by a laser pointer, and encouraged to swim towards it,” said Bjorn Mauck of the University of Southern Denmark and one of the team-members.

Wild Seals

Once the seals got the hang of navigating by the one star, the night sky above them was swivelled around and the seals were watched to see if they could still orientate themselves.

“With a little practice the seals swam in the right direction 100% of the time,” said Dr Mauck.

In the wild, seals’ foraging trips can take several days and so they often find themselves in open water with no visible landmarks for nights on end. How these wild seals learn the relationship between a star and their feeding ground is still unknown.

seal (G.Dehnhardt/MSC)

Hard work for captive seals used to study animal navigation

“Seals might learn the position of the stars relative to foraging grounds during dawn and dusk when they can see both the stars and landmarks at the coast,” suggests Dr Mauck.

The researchers think that marine mammals might use star paths, or “kaveingas” as Polynesian seafarers call them.

These people navigate by heading towards a star on the horizon until it moves too high to see, and then swap over to follow another star, and so on, guiding their way until dawn.

Seals, sealions and whales are often seen elevating themselves out of the water as they swim in open ocean. This act of coming out of the water vertically and staying above the surface momentarily, in the same way a human treads water, could allow marine mammals to set their course, the researchers speculate.

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Pet dogs can ‘catch’ human yawns


Yawning is known to be contagious in humans but now scientists have shown that pet dogs can catch a yawn, too.

The copying activity suggests that canines are capable of empathising with people, say the researchers who recorded dogs’ behaviour in lab tests.

Until now, only humans and their close primate relatives were thought to find yawning contagious.

The team – from Birkbeck College, University of London – reports its findings in Biology Letters.

Yawning, although sometimes a response to extreme stress, is more often a sign of tiredness; but the reason for why yawning is catching is not fully understood.

Human cues

There is evidence that autistic individuals are less inclined to yawn into response to another human yawning, suggesting that contagious yawning betrays an ability to empathise, explained Birbeck’s Dr Atsushi Senju.

Dr Senju and his team wondered whether dogs – that are very skilled at reading human social cues – could read the human yawn signal, and set out to test the yawning capabilities of 29 canines.

The team created two conditions, each five minutes long, in which a person – who was a stranger to the dog – was sat in front of the animal and asked to call its name. Under the first condition, the stranger yawned once the dogs had made eye contact with them.

“We gave dogs everything: visual and auditory stimulus to induce them to yawn,” Dr Senju, told BBC News.

Under the second condition, the same procedure was followed, but this time the stranger opened and closed their mouth but did not yawn.

This was a precaution to ensure that dogs were not responding to an open mouth, explained Dr Senju.

Yawning yet?

The team found that 21 out of 29 dogs yawned when the stranger in front of them yawned – on average, dogs yawned 1.9 times. By contrast, no dogs yawned during the non-yawning condition.

The researchers believe that these results are the first evidence that dogs have the capacity to empathise with humans; although the team could not rule out stress-induced yawning – they hope to in future studies.

“Dogs have a very special capacity to read human communication. They respond when we point and when we signal,” Dr Senju told BBC News.

The researchers explained that along with floppy ears and big soppy-eyes, humans have selected dogs to be obedient and docile. The results from this study suggest the capacity for empathy towards humans is another trait selected in dogs during domestication.

Dr Senju thinks that these traits would have been useful to humans when they began to live side-by-side with canines approximately 15,000 years ago.

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Southern seals sample salty seas

Southern seals

Elephant seals are helping scientists study temperature and salinity changes in the Southern Ocean.

Equipped with computerised tags, the seals can reach regions of the sea impenetrable to researchers during the harsh winter months.

The data, collected during the animals’ long dives under Antarctic ice, provide the best ever estimates for the rate of sea-ice formation.

The findings appear in the Proceedings of the National Academy of Sciences.

The tags measure position, salinity, and temperature, among other things, to form a “hydrographic profile” for each of the 58 seals fitted with a device.

“By using seals, we have increased the number of hydrographic profiles 30-fold,” said Jean-Benoit Charrassin, who is based in France’s Natural History Museum.

“What we know about the Southern Ocean is very limited, which makes predicting the formation of sea-ice difficult,” Dr Charrassin told BBC News.

“These animals are filling a ‘blind spot’ in our sampling.”

Plunging profile

Seals make excellent marine surveyors because they swim up to 100km a day and dive to depths of 2,000m (6600ft) during foraging trips.


Sea temperatures and salinity are measured by seal transmitters

Dr Charrassin told BBC News that seals returned to the surface to breathe about 60 times a day, spending three minutes, on average, bobbing there before descending again.

“Occasionally they stay long enough for the data loggers, atop their heads, to send the data via satellite,” explained the Paris-based researcher.

“On average, we can collect two profiles a day from each seal.”

Dr Charrassin said that by measuring the salinity of water beneath sea-ice, researchers could determine how quickly it formed.

“In the Antarctic, when seawater freezes to form sea-ice, the salt – usually suspended in the water – is ejected into the water beneath the ice,” he explained.

Previous measures of sea-ice – calculated by measuring the distances drifted by buoys over a three-week period – estimate that in August, it forms at a rate of 8-10cm (3-4in) per day.

Data collected by the seals allows better estimates and suggests that this rate is much lower – only 1cm (0.3 inches) per day.

 Seals often drift down to the bottom, seeming to sleep on their way down. 
Jean-Benoit Charrassin, SEaOS

Estimating the rate of formation of sea-ice is crucial to understanding ocean currents.

This super-salty water forms a dense layer below the ice and sinks.

The dense water then flows along the sea bottom into the ocean basins, forming part of the thermohaline circulation, a large-scale ocean current driven by global temperature and salt gradients.

This current helps redistribute energy and nutrients in the world’s oceans.

In the long-term, the researchers hope to continue using seals to help them monitor salinity levels in the Southern Ocean, and study the impact of global sea temperature changes on ocean currents.

Seal scoop

But what about the “furry oceanographers” themselves; what can tagging seals teach scientists about seal biology?

The data loggers, as well as measuring the seals’ environment, record diving depths and time spent at the sea-bottom, giving researchers a window into the seals’ deep-sea foraging behaviour.

“We wanted to understand the foraging ecology of elephant seals and study their role in the marine food web,” said Dr Charrassin.

“We think the seals [at the bottom] try to catch deep-dwelling animals like squid and fish – at these depths, the seals’ lungs and body can be compressed to overcome the great pressures at 2,000m,” he said.

Elephant seal populations (BBC)
South Georgian elephant seals represent about 50% of the 740,000 breeding population in the Sub-Antarctic

Differences in foraging behaviour might explain why the island populations of elephant seals on Kerguelen and Macquarie have seen large declines, while the 400,000-strong South Georgian population has remained stable since the 1950s.

The seals’ hydrographic profiles give more weight to this idea, showing that animals from Kerguelen generally feed on the Antarctic continental shelf, while South Georgian seals tend to feed in open ocean.

Further study into prey numbers in these different environments is needed to confirm the role of foraging behaviour in the decline of two of the three seal populations.

The research is a collaborative effort involving scientists from Europe, Australia and the US. It is part of the Southern Elephant Seals as Oceanographic Samplers (SEaOS) project that has been running for four years.

The scientists stress the animals are not bothered by the data loggers carried on their heads. The boxes are glued on to the fur of the seals and stay there for one year, until the animals moult.

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