Premature Aging Replicated in the Lab

The current pace of population aging is without parallel in human history but surprisingly little is known about the human aging process, because lifespans of eight decades or more make it difficult to study. Now, researchers at the Salk Institute for Biological Studies have replicated premature aging in the lab, allowing them to study aging-related disease in a dish.

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In the February 23, 2011 advance online edition of the journal Nature, Juan Carlos Izpisúa Belmonte, Ph.D. a professor in the Salk Institute's Gene Expression Laboratory, and his team report that they have successfully generated induced pluripotent stem (iPS) cells from skin cells obtained from patients with Hutchinson-Gilford Progeria Syndrome -- who age eight to 10 times faster than the rest of us -- and differentiated them into smooth muscle cells displaying the telltale signs of vascular aging.
"The slow progression and complexity of the aging process makes it very hard to study the pathogenesis of cardiovascular and other aging-related disorders," says Izpisúa Belmonte. "Having a human model of accelerated aging will facilitate the development of treatments and possibly a cure for Progeria and give us new insights into how we age. It may also help prevent or treat heart disease in the general aging population."
Progeria's striking features resemble the aging process put on fast-forward and afflicted people rarely live beyond 13 years. Almost all of the patients die from complications of arteriosclerosis -- the clogging or hardening of arteries or blood vessels caused by plaques -- which leads to heart attack and stroke.
Scientists are particularly interested in Progeria in the hopes that it might reveal clues to the normal human aging process. However, the disease is exceedingly rare and only 64 children living with Progeria are known making access to patients very difficult.
Hutchinson-Gilford Progeria Syndrome is caused by a single point mutation in the gene encoding lamin A, which forms a protein scaffold on the inner edge of the nucleus that helps maintain chromatin structure and organize nuclear processes such as RNA and DNA synthesis. The mutation creates an alternative splice site that leads to the production of a truncated version of the protein known as progerin. Unlike the full-length protein, progerin does not properly integrate into the nuclear lamina, which disrupts the nuclear scaffold and causes a host of problems.
"There is also evidence that defective lamin A accumulates during the normal aging process via the sporadic use of the alternative splice site, " explains Izpisua Belmonte. "Therefore we are very keen on using our in vitro iPS cell-based model to identify new aging markers and explore other aspects of human premature and physiological aging."
Compared to normal skin fibroblasts, cells from Progeria patients have misshapen nuclei and a range of other nuclear defects, including a disorganized nuclear lamina, loss of super-condensed DNA, telomere shortening and genomic instability. Yet, despite their "old" appearance and characteristics, these cells could be readily converted into iPS cells.
"The reprogramming process erased all nuclear and epigenetic defects and the rejuvenated pluripotent cells looked and acted like perfectly normal healthy cells," says first author Guang-Hui Liu, Ph.D., a postdoctoral researcher in the Belmonte lab.
Since lamin A is only expressed in differentiated cells but is absent from embryonic stem cells, he wondered whether iPS cells produce lamin A and/or progerin, which should follow the same expression pattern as lamin A. In his experiments, he couldn't detect either one. "The biological clock is reset in these cells because lamin A is silenced," explains Liu.
As soon as the Salk researchers differentiated Progeria-derived iPS cells, progerin expression was reactivated. "This reversible suppression of progerin expression by reprogramming and subsequent reactivation during differentiation, provides a unique model system to study human premature aging pathologies," says Izpisúa Belmonte.
Progerin accumulates mainly in smooth muscle cells found within the walls of arterial blood vessels, and vascular smooth muscle cells degeneration is one of the hallmarks of Hutchinson-Gilford Progeria Syndrome-associated arteriosclerosis. In fact, vascular smooth muscle cell senescence also plays a role in advanced arteriosclerosis within the normal aging population.
Upon directed differentiation of Progeria-derived iPS cells into smooth muscle cells the premature aging phenotype, including misshapen nuclei, the loss of gene silencing marks and compromised proliferation, reappeared. Genetically modifying progeria-derived iPS cells to shut down the expression of progerin staved off the premature appearance of aging phenotypes after differentiation. "Transplantation of the progenitor cells derived from the "corrected" progeria iPS cells might hold the promise to treat these progeria children in the future." says Liu.
Other researchers contributing the study include Basam Z. Barkho, Sergio Ruiz, Jing Qu, Scheng-Liang Yang, Athanasia D. Panopoulos, Keiichiro Suzuki, Leo Kuraian, Christopher Walsh and Ignacio Sancho-Martinez in the Gene Expression Laboratory at the Salk Institute, Dinh Diep and Ho Lim Fung in the Department of Engineering at the University of California, San Diego, James Thompson and John Yates III in the Department of Cell Biology at the Scripps Research Institute and Stephanie Boue at the Center for Regenerative Medicine in Barcelona.
The study was supported by the California Institute of Regenerative Medicine, the AFAR/Ellison Medical Foundation, the G. Harold and Leila Y. Mathers Charitable Foundation, Sanofi-Aventis, MICINN, the Fundacion Cellex and grants from the National Institutes of Health.

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Left: Juan Carlos Izpisúa Belmonte, Ph.D. a professor in the Salk Institute's Gene Expression 

Solar Experts Detect Waves in Giant Magnetic Holes the Size of the UK

ScienceDaily (Feb. 25, 2011) — Massive waves in giant magnetic holes on the surface of the Sun have been discovered for the first time by solar scientists from the University of Sheffield and Queen´s University Belfast, something that will bring experts a step closer to unlocking the secrets of the Sun.

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The Sun is interwoven by a complex network of magnetic field lines that are responsible for a large variety of fascinating features that can be seen in the solar atmosphere. Large, dark regions, which look like holes on the Sun´s surface, mark out areas where the magnetic field breaks through from the Sun´s deep, boiling interior and rises into the very hot solar atmosphere, which is over a million degrees. The largest of these dark regions are often called sunspots and have been studied since their discovery from as early as 364 BC.
Led by Professor Robertus von Fay-Siebenburgen, Head of the Solar Physics and Space Plasma Research Centre (SP2RC) at the University of Sheffield, the team studied a magnetic region of the Sun much smaller than a sunspot, however its size was still many times greater than the size of the UK.
Their research, which was published this week in Astrophysical Journal, has shown that the magnetic hole they observed, which is also known as a pore, is able to channel energy generated deep inside the Sun, along the magnetic field to the Sun´s upper atmosphere. The magnetic field emerging through the pore is over 1,000 times stronger than the magnetic field of Earth.The energy being transported is in the form of a very special form of waves, known as `sausage waves´ which the scientists were able to observe using a UK-built solar imager known as ROSA (Rapid Oscillations of the Solar Atmosphere), which was designed by Queen´s University Belfast and is in operation at the Dunn Solar Telescope, Sacramento Peak, USA. This is the first direct observation of `sausage waves´ at the solar surface. The magnetic hole is seen to increase and decrease in size periodically which is a characteristic feature of the `sausage wave.´
The team of experts, including Dr Richard Morton from the University of Sheffield, as well as Professor Mihalis Mathioudakis and Dr David Jess from Queen´s University Belfast, hope these giant magnetic holes will play an important role in unveiling the longstanding secrets behind solar coronal heating.
This is because the solar surface has a temperature of a few thousand degrees but the solar corona -- the outermost, mysterious, and least understood layer of the Sun's atmosphere -- is heated to temperatures often a thousand times hotter than the surface. Why the temperature of the Sun´s atmosphere increases as we move further away from the centre of energy production, which lies under the surface, is a great mystery of astrophysics. The findings, which demonstrate the transfer of energy on a massive scale, offer a new explanation for this puzzle.
The team now hope to use further similar solar images from ROSA to understand the fine substructure of these massive magnetic holes by reconstructing the images to view what is inside the holes.
Professor Robertus von Fay-Siebenburgen, said: "This is a fascinating new discovery in line with a number of discoveries made in recent years by the team. It is the first time that `sausage waves´ have been detected in the Sun with such detail. Analysing these waves may bring us closer to understanding the physical mechanisms in the atmosphere of a star.

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This shows the chromosphere of the solar atmosphere. Bright patches correspond to concentrated magnetic flux.

Gas Rich Galaxies Confirm Prediction of Modified Gravity Theory

ScienceDaily (Feb. 25, 2011) — Recent data for gas rich galaxies precisely match predictions of a modified theory of gravity known as MOND, according to a new analysis by University of Maryland Astronomy Professor Stacy McGaugh. This -- the latest of several successful MOND predictions -- raises new questions about accuracy of the reigning cosmological model of the universe, writes McGaugh in a paper to be published in March in Physical Review Letters.

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Modern cosmology says that for the universe to behave as it does, the mass-energy of the universe must be dominated by dark matter and dark energy. However, direct evidence for the existence of these invisible components remains lacking. An alternate, though unpopular, possibility is that the current theory of gravity does not suffice to describe the dynamics of cosmic systems.
A few theories that would modify our understanding of gravity have been proposed. One of these is Modified Newtonian Dynamics (MOND), which was hypothesized in 1983 by Moti Milgrom a physicist at the Weizmann Institute of Science in Rehovot, Israel. One of MOND's predictions specifies the relative relationship between the mass of any galaxy and its flat rotation velocity. However, uncertainties in the estimates of masses of stars in star-dominated spiral galaxies (such as our own Milky Way) previously had precluded a definitive test.
To avoid this problem, McGaugh examined gas rich galaxies, which have relatively fewer stars and a preponderance of mass in the form of interstellar gas. "We understand the physics of the absorption and release of energy by atoms in the interstellar gas, such that counting photons is LIKE counting atoms. This gives us an accurate estimate of the mass of such galaxies," McGaugh said.
Using recently published work that he and other scientists had done to determine both the mass and flat rotation velocity of many gas rich galaxies, McGaugh compiled a sample of 47 of these and compared each galaxy's mass AND rotation velocity with the relationship expected by MOND. All 47 galaxies fell on or very close to the MOND prediction. No dark matter model performed as well.
"I find it remarkable that the prediction made by Milgrom over a quarter century ago performs so well in matching these findings for gas rich galaxies," McGaugh said. "
MOND vs. Dark Matter -- Dark Energy
Almost everyone agrees that on scales of large galaxy clusters and up, the Universe is well described by dark matter -- dark energy theory. However, according to McGaugh this cosmology does not account well for what happens at the scales of galaxies and smaller.
"MOND is just the opposite," he said. "It accounts well for the 'small' scale of individual galaxies, but MOND doesn't tell you much about the larger universe.
Of course, McGaugh said, one can start from the assumption of dark matter and adjust its models for smaller scales until it fits the current finding. "This is not as impressive as making a prediction ahead of [new findings], especially since we can't see dark matter. We can make any adjustment we need." This is rather like fitting planetary orbits with epicycles," he said. Epicycles were erroneously used by the ancient Greek scientist Ptolemy to explain observed planetary motions within the context of a theory for the universe that placed Earth in its center.
"If we're right about dark matter, why does MOND work at all?" asks McGaugh. "Ultimately, the correct theory -- be it dark matter or a modification of gravity -- needs to explain this."

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The star dominated spiral galaxy UGC 2885. (Credit: Zagursky & McGaugh)

Rocket-related Issue Pushes Glory Launch into March

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The Taurus XL launch for NASA's Glory spacecraft from Vandenberg Air Force Base has been delayed due to technical issues. Credit: U.S. Air Force photo Enlarge Image

WASHINGTON — NASA has temporarily suspended preparations to launch its Glory climate observation satellite after a malfunction occurred with the ground support equipment for the Taurus XL rocket that will carry the satellite into its polar orbit, the agency announced Feb. 24.

About 15 minutes before Glory was to launch Feb. 23, launch managers received a false indication about the status of the rocket, NASA said in a press release. The source of the problem has not yet been identified, and NASA is now evaluating possible launch opportunities in early to mid-March, it said.

The Glory satellite, built by Orbital Sciences Corp. of Dulles, Va., is designed to study solar irradiance and aerosol particles in the Earth’s atmosphere that are believed to be associated with global climate change.

The Taurus XL rocket, also built by Orbital Sciences, is making its return to flight two years after a launch failure that destroyed NASA’s Orbiting Carbon Observatory satellite.

Ancient fossil sheds light on early evolution of body armor

‘Walking cactus’ appears to have been first of its kind to stride on bendable, hard-covered legs

By Susan Milius

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MEET SPIKYA depiction of the 520-million-year-old fossil Diania cactiformis in life. The front of the animal is to the left.J. Liu

Fossils of an ancient “walking cactus” suggest how ancestors of today’s lobsters, insects, spiders and related groups went from squishy to spiky.
Dating back about 520 million years, the fossilized prickly creature is not a plant but a thumb-sized, wormlike animal with 10 pairs of long, sturdy legs, says Jianni Liu of Northwest University in Xi’an, China. Discovered in southwestern China, it probably scuttled along the bottom of shallow seas, she says. In the Feb. 24 Nature, she and her colleagues christen the species Diania cactiformis, in honor of its spiky look.
Its armored leggy look surprised Liu when she first saw it. “I fell in love with this strange guy,” she says. “Later when I observed it carefully under the microscope, I realized it was not only a funny one but an important one.”

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WHAT LEGSOne of the best-preserved fossils of the newly named Diania cactiformis reveals spiky legs that researchers interpret as having hard outer coverings and joints.J. Liu

The creature’s 10 legs appear to have carried a hard, outer covering of armor and joints that let them bend. Those features would make the species the earliest known worm-with-legs to have a hardened outer covering and also the first to have jointed legs, Liu says. An armored outer skeleton and jointed legs today distinguish the arthropods, the major lineage including crustaceans, insects, spiders and mites. Thus the cactus sea creature might be a sister to arthropod ancestors.
“The significance of the find is that arthropods are, in terms of species, the most successful group on the planet,” Liu says. “The secret of their success seems to be their legs.” Ancient appendages evolved with diverse lifestyles, forming claws for example, or gilled structures for underwater life. Even legs for moving around diversified into paddles for swimming or launchers for jumping.
Liu points out that paleontologists pursuing the history of the remarkable arthropod legs have debated such puzzles as whether the armored bodies came before or after armored legs.
The presumably armored legs of this animal show how a legs-first scenario might look, but Liu notes that there’s no evidence that this is a direct ancestor of modern arthropods.
Jan Bergström of the Swedish Museum of Natural History in Stockholm laments the fact that it’s not a direct ancestor, but says the new fossil “fills a hole in the evolutionary mosaic.”

Ancient Catastrophic Drought Leads to Question: How Severe Can Climate Change Become?

ScienceDaily (Feb. 24, 2011) — How severe can climate change become in a warming world? Worse than anything we've seen in written history, according to results of a study recently appearing in the journal Science.

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An international team of scientists led by Curt Stager of Paul Smith's College, New York, has compiled four dozen paleoclimate records from sediment cores in Lake Tanganyika and other locations in Africa.
The records show that one of the most widespread and intense droughts of the last 50,000 years or more struck Africa and Southern Asia 17,000 to 16,000 years ago.
Between 18,000 and 15,000 years ago, large amounts of ice and meltwater entered the North Atlantic Ocean, causing regional cooling but also major drought in the tropics, says Paul Filmer, program director in the National Science Foundation's (NSF) Division of Earth Sciences, which funded the research along with NSF's Division of Atmospheric and Geospace Sciences and its Division of Ocean Sciences.
"The height of this time period coincided with one of the most extreme megadroughts of the last 50,000 years in the Afro-Asian monsoon region with potentially serious consequences for the Paleolithic humans that lived there at the time," says Filmer.
The "H1 megadrought," as it's known, was one of the most severe climate trials ever faced by anatomically modern humans.
Africa's Lake Victoria, now the world's largest tropical lake, dried out, as did Lake Tana in Ethiopia, and Lake Van in Turkey.
The Nile, Congo and other major rivers shriveled, and Asian summer monsoons weakened or failed from China to the Mediterranean, meaning the monsoon season carried little or no rainwater.
What caused the megadrought remains a mystery, but its timing suggests a link to Heinrich Event 1 (or "H1"), a massive surge of icebergs and meltwater into the North Atlantic at the close of the last ice age.
Previous studies had implicated southward drift of the tropical rain belt as a localized cause, but the broad geographic coverage in this study paints a more nuanced picture.
"If southward drift were the only cause," says Stager, lead author of the Science paper, "we'd have found evidence of wetting farther south. But the megadrought hit equatorial and southeastern Africa as well, so the rain belt didn't just move--it also weakened."
Climate models have yet to simulate the full scope of the event.
The lack of a complete explanation opens the question of whether an extreme megadrought could strike again as the world warms and de-ices further.
"There's much less ice left to collapse into the North Atlantic now," Stager says, "so I'd be surprised if it could all happen again--at least on such a huge scale."
Given what such a catastrophic megadrought could do to today's most densely populated regions of the globe, Stager hopes he's right.
Stager also holds an adjunct position at the Climate Change Institute, University of Maine, Orono.
Co-authors of the paper are David Ryves of Loughborough University in the United Kingdom; Brian Chase of the Institut des Sciences de l'Evolution de Montpellier in France and the Department of Archaeology, University of Bergen, Norway; and Francesco Pausata of the Geophysical Institute, University of Bergen, Norway.

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Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.

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A wetland along Lake Victoria today, analogous to ancient drought conditions. (Credit: Curt Stager)

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Apple shareholders nix CEO succession disclosure

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CUPERTINO, Calif.--Apple shareholders today rejected a proposal that would have required the company to disclose its succession plan for senior management.
The proposal was one of two by shareholders aimed at adding transparency and a new voting standard to what is considered one of the most secretive technology companies. In its proxy materials ahead of the meeting, Apple's board had urged shareholders to vote against both proposals.

As expected, Jobs was not present during the meeting. In his place was Chief Operating Officer Tim Cook, who has filled in for Jobs since January when Jobs, a pancreatic cancer survivor who has received a liver transplant, announced his latest medical leave.
A group of shareholders had asked the company to reveal its plans for replacing Jobs, a request Apple had rallied against, saying such a revelation would give competitors an "unfair advantage" by publicizing the company's confidential objectives and plans. Nonetheless, earlier in the month Institutional Shareholder Services endorsed the proposal, which was originally put forward by the Central Laborers' Pension Fund, a holder of about 11,500 shares of Apple stock.
The second proposal, which concerned majority voting of board members, passed, giving share owners the power to cast Nay votes against unopposed directors. Apple said its objection to the measure was based on differences in majority voting requirements by state, which, the company said, could add a "layer of complexity" to implementation.
During the question and answer session that followed, Cook was joined on stage by Phil Schiller, senior vice president of worldwide product marketing, and Peter Oppenheimer, senior vice president and CFO. Cook talked up Apple's services over the past year, including its opening of 44 new retail stores and shipping of 40 million iPhones, doubling unit sales from the previous year. Cook also said the company had made great advances in China, tripling revenue there since last year.

Pixelated motif on signage at Apple's Cupertino, Calif., campus.

(Credit: Josh Lowensohn/CNET)

Cook paid special attention to iOS, including the iPhone and iPad, saying that the OS continued to be "years ahead" of competitors' platforms. Cook also brought up next week's press event, saying that the invitation had provided some clues about what Apple planned to announce. Even so, audience members peppered the company about its strategic plans for iOS, including things like whether it would ever allow plug-ins, or how Apple could avoid the sort of hardware-specific software distribution limitations it experienced during the Mac versus PC era in the early '90s, which went Microsoft's way.
Schiller responded by saying that that had been "a different time," and that the iPhone was a "post-PC" product. Apple's senior vice president of iOS Software, Scott Forstall, jumped in on the third-party plug-ins question, saying that plug-ins had been kept off the platform for stability and security, citing some of the difficulties in moving from Mac OS 7 to 8 as being a leading factor in that decision.
One audience member also brought up the conditions for workers at overseas factories where Apple products were produced, as well as asking if Cook, Schiller, or Oppenheimer had seen the play "The Agony and Ecstasy of Steve Jobs," playing about an hour away from Apple's campus, at the Berkeley Repertory Theatre. All three said they hadn't, with Schiller seeming visibly frustrated by the question.
Cook followed by offering details about Apple's considerable efforts to go through its supply chain to find problems that could be fixed, as well as noting that the company had helped reimburse close to $300 million in fees paid by workers. "I am really proud of the changes we've forced," Cook said.
Also of special interest was a question about whether Apple would ever offer a way for consumers to ditch their television sets to watch streaming TV shows on their computers instead. Schiller answered by saying that Apple was always adding "new types" of media. Even so, he said, counting out the TV at this point for live events would be a rash decision.
And speaking of entertainment devices, Cook fielded a question about whether Apple had plans to get more serious about gaming, particularly with a dedicated device, by saying that the company was already in the gaming business with the iPod Touch, and had great success with a large library of games on the App Store. "There's a segment who are using it as a primary gaming device," he said. "We think that's a good place to be, where we are right now."
One audience member also questioned what Apple was up to with its license of Liquidmetal, a query Cook politely shot down, saying the company does not discuss what it does with its investments short of saying that such investments were often for personnel, infrastructure, and intellectual property.