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Hubble captures bubbles and baby stars
Hubble captures bubbles and baby stars (6/22/10)
N11 – click for 2500×2458 image
More: here
The NASA/ESA Hubble Space Telescope captures a complex network of gas clouds and star clusters within our neighbouring galaxy, the Large Magellanic Cloud. This region of energetic star birth is one of the most active in the nearby Universe.
The Large Magellanic Cloud contains many bright bubbles of glowing gas. One of the largest and most spectacular is LHA 120-N 11, from the catalogue compiled in 1956 by the late astronomer and astronaut Karl Henize. It is informally known as N11.
Close up, N11’s billowing pink clouds of glowing gas resemble a puffy swirl of fairground candyfloss. From further away, its distinctive overall shape led some observers to nickname it the Bean Nebula. The dramatic and colourful features in the nebula are the telltale signs of star birth.
N11 is a well-studied region that extends across 1000 light-years. It is the second largest star-forming region within the Large Magellanic Cloud and has produced some of the most massive stars known.
N11 – click for 2500×2458 image
More: here
Selected readings 9/28/10
Interesting reading and news items.
Please leave some comments that indicate which articles you find most interesting or that identify topics you would like to read about, and I will try to include more articles of a similar nature in the future
These items are also bookmarked at my Diigo account.
RSS access:
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Items saved at Diigo
Please leave some comments that indicate which articles you find most interesting or that identify topics you would like to read about, and I will try to include more articles of a similar nature in the future
These items are also bookmarked at my Diigo account.
- Convincing a Young Scientist that Dark Matter Exists
- So I was in favor of dark matter, but I wasn't entirely convinced. I wanted a "smoking gun" piece of evidence for dark matter. Something that was an entirely new prediction that we could look for -- much like that 1919 eclipse was for general relativity -- and decide whether dark matter predicts what we're going to see. [Starts with a Bang, 6/24/10]
- How blind to change are you?
- This failure to notice what should be very apparent is something we unconsciously experience every day as our brains filter the barrage of visual information which we are flooded with. And apparently it has a name; it is called change blindness. [BBC News, 6/11/10]
- New data suggest a lighter Higgs
- New data offer evidence that the heft of the Higgs particle lies somewhere in the low end of the range being probed by particle colliders on two continents. The results also hint that the particle’s mass may be consistent with supersymmetry, a theory that gives every particle in the standard model of physics a much heavier partner. [Science News, 7/26/10]
- Jellyfish eye genes suggest a common origin for animal eyes
- Jellyfish may seem like simple blobs but some have surprisingly sophisticated features, including eyes. These are often just light-sensitive pits but species like the root-arm medusa have complex ‘camera’ eyes, with a lens that focuses light onto a retina. Not only are these organs superficially similar to ours, they’re also constructed from the same genetic building blocks. [Not Exactly Rocket Science, 7/27/10]
- Astronomy and particle physics race to replace Standard Model
- If energy issues seem to be attracting the attention of a lot of physicists, the Large Hadron Collider seems to be drawing the attention of many of the rest of them, including people in fields like cosmology, which deals with items on the opposite end of the size scale. In turn, the people working on the LHC and other particle detectors are carefully paying attention to the latest astronomy results, hoping they'll put limits on the properties and identities of the zoo of theoretical particles that need to be considered. [Nobel Intent, 7/28/10]
- Genetics tells tall tales
- Studies scanning the genomes of tens of thousands of individuals for gene variants associated with height have come up short: around 50 variants have been identified, but together they account for only 5% or so of height's heritability. ... This heritability may not be missing — it may simply be buried deeper than previously thought, in a multitude of genetic variants that have tiny effects individually. [Nature News, 6/20/10]
- Dark matter eldorado
- Observations confirm that a faint group of stars in the Milky Way’s backyard has the highest density of dark matter — the invisible material thought to account for 83 percent of the mass of the universe — of any galaxy known. [Science News, 7/30/10]
- Searching through the LHC data flood for dark matter
- Although the Standard Model has needed some minor tweaking to deal with recent observations, Gross said that there are three major issues that suggests it's due for a major overhaul. One of these is that we have convincing evidence that dark matter exists, and comes in the form of particles that are heavy and stable to at least the life of the Universe. Unfortunately, the Standard Model provides nothing that meets these requirements. [Nobel Intent, 8/1/10]
- Two New Paths to the Dream: Regeneration
- Animals like newts and zebra fish can regenerate limbs, fins, even part of the heart. If only people could do the same, amputees might grow new limbs and stricken hearts be coaxed to repair themselves. But humans have very little regenerative capacity, probably because of an evolutionary trade-off: suppressing cell growth reduced the risk of cancer, enabling humans to live longer. A person can renew his liver to some extent, and regrow a fingertip while very young, but not much more. [New York Times, 8/5/10]
- Sponge genes surprise
- A complete genetic catalog of the sponge Amphimedon queenslandica suggests that the first animals already had a complex kit of genetic tools at their disposal. Sponges harbor between 18,000 and 30,000 genes — roughly the same number as humans, fruit flies, roundworms and other animals. [Science News, 8/4/10]
- Plentiful and Potential Planets
- Two planet-hunting telescopes - CoRoT and Kepler - are keeping astronomers hard at work cataloging far-distant planets that orbit other stars in our galaxy. The search for distant planets is essential for astrobiologists who are hunting for habitable, Earth-like worlds beyond our solar system. [Physorg.com, 6/23/10]
- World’s Most Intense X-Ray Laser Takes First Shots
- The world’s most intense X-ray laser may soon be the fastest strobe-light camera ever. Two of the laser’s first experiments show the device will be able to take snapshots of single molecules in motion — without destroying them first. [Wired Science, 6/30/10]
- The origin of life: putting chemistry inside a cell
- In Szostak's view, interesting chemistry is easy. He also said that Darwinian evolution also makes things easy, since it's possible to take what you've got and radically improve it. So what's bugging him these days is the transition in between the two. How do you move from interesting chemistry to something that can evolve? He's doing this by trying to engineer a system that can make the transition. [Nobel Intent, 6/28/10]
- Why weather != climate: the engine behind climate models
- In this article I take a look at climate modeling and in particular why the comment "They can't predict the weather, therefore climate models are not good" is just plain wrong. It represents a fundamental misunderstanding of what climate modelers are trying to achieve, what is achievable and why the weather is unpredictable. [Nobel Intent, 7/9/10]
- Does Your Language Shape How You Think?
- The habits of mind that our culture has instilled in us from infancy shape our orientation to the world and our emotional responses to the objects we encounter, and their consequences probably go far beyond what has been experimentally demonstrated so far; they may also have a marked impact on our beliefs, values and ideologies. We may not know as yet how to measure these consequences directly or how to assess their contribution to cultural or political misunderstandings. But as a first step toward understanding one another, we can do better than pretending we all think the same. [New York Times, 8/26/10]
- Stem Cell Biology and Its Complications
- Stem cell biology turned out to be more complicated than they anticipated. Besides the stem cells from embryos, there are so-called adult stem cells found in all tissues but with limited potential because they can only turn into cells from their tissue of origin. And there are these newer cells made by reprogramming mature cells. [New York Times, 8/24/10]
- Scientists Square Off on Evolutionary Value of Helping Relatives
- For the past 46 years, biologists have used Dr. Hamilton’s theory to make sense of how animal societies evolve. They’ve even applied it to the evolution of our own species. But in the latest issue of the journal Nature, a team of prominent evolutionary biologists at Harvard try to demolish the theory. [New York Times, 8/30/10]
- Think You're Operating on Free Will? Think Again
- There may be few things more fundamental to human identity than the belief that people are rational individuals whose behavior is determined by conscious choices. But recently psychologists have compiled an impressive body of research that shows how deeply our decisions and behavior are influenced by unconscious thought, and how greatly those thoughts are swayed by stimuli beyond our immediate comprehension. [Time, 7/2/10]
- Forget What You Know About Good Study Habits
- In recent years, cognitive scientists have shown that a few simple techniques can reliably improve what matters most: how much a student learns from studying. The findings can help anyone, from a fourth grader doing long division to a retiree taking on a new language. But they directly contradict much of the common wisdom about good study habits, and they have not caught on. [New York Times, 9/6/10]
- Gene networks underlie disease?
- An international group of researchers have developed a novel method for identifying entire networks of genes and their association to disease, providing a more accurate picture of the genetic risks associated with specific diseases than single genes can provide. [The Scientist, 9/8/10]
- Collider gets yet more exotic 'to-do' list
- As if the Large Hadron Collider (LHC) didn't have enough to look for. It is already charged with hunting for the fabled Higgs boson, extra dimensions and supersymmetry, but physicists are now adding even more elaborate phenomena to its shopping list — including vanishing dimensions that could explain the accelerating expansion of the Universe. Some argue that signs of new and exotic physics could show up in the LHC far sooner than expected. [Nature News, 7/20/10]
- Under Pressure: The Search for a Stress Vaccine
- Chronic stress, it turns out, is an extremely dangerous condition. ... While stress doesn’t cause any single disease — in fact, the causal link between stress and ulcers has been largely disproved — it makes most diseases significantly worse. The list of ailments connected to stress is staggeringly diverse and includes everything from the common cold and lower-back pain to Alzheimer’s disease, major depressive disorder, and heart attack. [Wired Magazine, 7/28/10]
- Why some memories stick
- A study published in Science this week indicates that reactivating neural patterns over and over again may etch items into the memory. People find it easier to recall things if material is presented repeatedly at well-spaced intervals rather than all at once. For example, you're more likely to remember a face that you've seen on multiple occasions over a few days than one that you've seen once in one long period. One reason that a face linked to many different contexts — such as school, work and home — is easier to recognize than one that is associated with just one setting, such as a party, could be that there are multiple ways to access the memory. This idea, called the encoding variability hypothesis, was proposed by psychologists about 40 years ago. [Nature News, 9/9/10]
- DNA 'Volume Knobs' May Be Associated With Obesity
- When it comes to our expanding waistlines, we usually blame either diet or genes. But a new study fingers a third culprit: chemicals that attach to DNA and change its function. A survey of millions of these modifications has uncovered a handful associated with body mass index, a measure of height and weight. [Science Now, 9/15/10]
- Astronomy and particle physics race to replace Standard Model
- If energy issues seem to be attracting the attention of a lot of physicists, the Large Hadron Collider seems to be drawing the attention of many of the rest of them, including people in fields like cosmology, which deals with items on the opposite end of the size scale. In turn, the people working on the LHC and other particle detectors are carefully paying attention to the latest astronomy results, hoping they'll put limits on the properties and identities of the zoo of theoretical particles that need to be considered. [Nobel Intent, 7/28/10]
- Sizing Up Consciousness by Its Bits
- Consciousness, Dr. Tononi says, is nothing more than integrated information. Information theorists measure the amount of information in a computer file or a cellphone call in bits, and Dr. Tononi argues that we could, in theory, measure consciousness in bits as well. When we are wide awake, our consciousness contains more bits than when we are asleep. [New York Times, 9/20/10]
- Translating Stories of Life Forms Etched in Stone
- The Ediacaran fossils tell us that Darwin was being too generous. Our earliest animal ancestor probably had no head, tail, or sexual organs, and lay immobile on the sea floor like a door mat. [New York Times, 7/26/10]
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A Galactic Spectacle
A Galactic Spectacle (8/5/10)
Antennae Galaxies – click for 851×864 image
The Antennae galaxies, located about 62 million light years from Earth, are shown in this composite image from the Chandra X-ray Observatory (blue), the Hubble Space Telescope (gold and brown), and the Spitzer Space Telescope (red). The Antennae galaxies take their name from the long antenna-like "arms," seen in wide-angle views of the system. These features were produced by tidal forces generated in the collision.
The collision, which began more than 100 million years ago and is still occurring, has triggered the formation of millions of stars in clouds of dusts and gas in the galaxies. The most massive of these young stars have already sped through their evolution in a few million years and exploded as supernovas.
The X-ray image from Chandra shows huge clouds of hot, interstellar gas that have been injected with rich deposits of elements from supernova explosions. This enriched gas, which includes elements such as oxygen, iron, magnesium and silicon, will be incorporated into new generations of stars and planets.
Antennae Galaxies – click for 851×864 image
An Elegant Galaxy in an Unusual Light
An Elegant Galaxy in an Unusual Light (9/22/10)
NGC 1365 – click for 1280×1271 image
A new image taken with the powerful HAWK-I camera on ESO’s Very Large Telescope at Paranal Observatory in Chile shows the beautiful barred spiral galaxy NGC 1365 in infrared light. NGC 1365 is a member of the Fornax cluster of galaxies, and lies about 60 million light-years from Earth. ...
The new infrared images from HAWK-I are less affected by the dust that obscures parts of the galaxy than images in visible light and they reveal very clearly the glow from vast numbers of stars in both the bar and the spiral arms. These data were acquired to help astronomers understand the complex flow of material within the galaxy and how it affects the reservoirs of gas from which new stars can form. The huge bar disturbs the shape of the gravitational field of the galaxy and this leads to regions where gas is compressed and star formation is triggered. Many huge young star clusters trace out the main spiral arms and each contains hundreds or thousands of bright young stars that are less than ten million years old. The galaxy is too remote for single stars to be seen in this image and most of the tiny clumps visible in the picture are really star clusters. Over the whole galaxy, stars are forming at a rate of about three times the mass of our Sun per year.
While the bar of the galaxy consists mainly of older stars long past their prime, many new stars are born in stellar nurseries of gas and dust in the inner spiral close to the nucleus. The bar also funnels gas and dust gravitationally into the very centre of the galaxy, where astronomers have found evidence for the presence of a super-massive black hole, well hidden among myriads of intensely bright new stars.
NGC 1365 – click for 1280×1271 image
An "Island Universe" in the Coma Cluster
An "Island Universe" in the Coma Cluster (8/10/10)
NGC 4911 – click for 1280×1109 image
A long-exposure Hubble Space Telescope image shows a majestic face-on spiral galaxy located deep within the Coma Cluster of galaxies, which lies 320 million light-years away in the northern constellation Coma Berenices.
The galaxy, known as NGC 4911, contains rich lanes of dust and gas near its center. These are silhouetted against glowing newborn star clusters and iridescent pink clouds of hydrogen, the existence of which indicates ongoing star formation. Hubble has also captured the outer spiral arms of NGC 4911, along with thousands of other galaxies of varying sizes. The high resolution of Hubble's cameras, paired with considerably long exposures, made it possible to observe these faint details.
NGC 4911 and other spirals near the center of the cluster are being transformed by the gravitational tug of their neighbors. In the case of NGC 4911, wispy arcs of the galaxy's outer spiral arms are being pulled and distorted by forces from a companion galaxy (NGC 4911A), to the upper right. The resultant stripped material will eventually be dispersed throughout the core of the Coma Cluster, where it will fuel the intergalactic populations of stars and star clusters.
NGC 4911 – click for 1280×1109 image
Selected readings 10/24/10
Interesting reading and news items.
Please leave some comments that indicate which articles you find most interesting or that identify topics you would like to read about, and I will try to include more articles of a similar nature in the future
These items are also bookmarked at my Diigo account.
RSS access:
Blog posts labeled "readings"
Items saved at Diigo
Please leave some comments that indicate which articles you find most interesting or that identify topics you would like to read about, and I will try to include more articles of a similar nature in the future
These items are also bookmarked at my Diigo account.
- The New Nu News!
- There could be an extra, "sterile" neutrino out there, although cosmology places tight restrictions on that. There could be a fundamental difference between neutrinos and anti-neutrinos, which we don't (at present) understand at all. Or there could be some physics that's completely off the radar that explains this, but it looks like the good ol' standard model (and the simplest modifications to it) is woefully inadequate to explain what we're seeing. [Starts with a Bang, 9/27/10]
- Primordial Magnetic Field May Permeate the Universe
- Two physicists attempting to overcome some unexpected fuzziness in images of distant, supermassive black holes say they have found yet another potential big bang vestige: an extremely weak magnetic field that stretches across the universe. If scientists confirm the finding, it could help reveal the origins of magnetism in the cosmos. [ScienceNOW, 9/24/10]
- The Itch of Curiosity
- Curiosity is one of those personality traits that gets short scientific shrift. It strikes me as a really important mental habit - how many successful people are utterly incurious? - but it's also extremely imprecise. What does it mean to be interested in seemingly irrelevant ideas? And how can we measure that interest? While we've analyzed raw intelligence to death - scientists are even beginning to unravel the anatomy of IQ - our curiosity about the world remains mostly a mystery. [Wired, 8/3/10]
- The Personality Paradox
- There's an interesting new paper in Biological Psychiatry on the genetic variations underlying human personality. The study relied on a standard inventory of temperaments - novelty-seeking, harm avoidance, reward dependence and persistence - as measured in 5,117 Australian adults. What did the scientists find? Mostly nothing. The vast genetic search came up empty. [Wired, 8/9/10]
- The Worm In Your Brain
- So our cortex turns out to be a lot older than previously thought. The common ancestor of us and ragworms–a wormy creature that lived 600 million years ago–not only had a brain, but had an ur-cortex. And it probably used that ur-cortex to learn about its world–most likely learning about the odors it sniffed. That animal’s descendants diverged into different forms, and the ur-cortex changed along the way. Yet they still used many of the same genes their ancestor did long ago. [The Loom, 9/3/10]
- Mapping the Brain on a Massive Scale
- A massive new project to scan the brains of 1,200 volunteers could finally give scientists a picture of the neural architecture of the human brain and help them understand the causes of certain neurological and psychological diseases. The National Institutes of Health announced $40 million in funding this month for the five-year effort, dubbed the Human Connectome Project. Scientists will use new imaging technologies, some still under development, to create both structural and functional maps of the human brain. [Technology Review, 9/28/10]
- Recipes For Limb Renewal
- Bioengineers continue to refine prosthetic limbs, but they still can’t replicate the entire constellation of capabilities provided by flesh and blood. So a few determined scientists are pursuing a different solution: They are seeking the recipe for regrowing a missing limb. [Chemical & Engineering News, 8/2/10]
- If low serotonin levels aren't responsible for depression, what is?
- While traditional antidepressants do increase neurogenesis and relieve depression symptoms in some animal models, others show that neurogenesis and antidepressant behaviours are unrelated. Much of this debate comes down to the fact that we don't yet have a real understanding of neurogenesis, how it works, and how it is controlled both in normal brains and in the presence of antidepressants. Until we know, finding a truly effective antidepressant may remain out of reach. So while the monoamine/serotonin hypothesis for depression may be out, neurogenesis needs to step it up a little to make it in. [guardian.co.uk, 9/28/10]
- A New Way to Make Stem Cells
- A Harvard researcher has developed a way to make pluripotent stem cells that solves several of the major impediments to using them to treat human diseases. Derrick Rossi, an assistant professor at Harvard Medical School, created pluripotent stem cells--which can turn into virtually any other type of cell in the body--from non-stem cells without using viruses to tinker with a cell's genome, as conventional methods do. This means that Rossi's method could be substantially safer for treating disease. [Technology Review, 10/1/10]
- Alien World Tour: The Exoplanets Around Star Gliese 581
- The announcement Wednesday (Sept. 29) of two newfound alien planets circling the star Gliese 581 adds to the nearby solar system's intrigue, further cementing its status as a top candidate to harbor extraterrestrial life. One of the two newly discovered planets, known as Gliese 581g, is a small, Earth-like world that likely lies within its star's habitable zone - the just-right range of distances that allow liquid water to exist. Astronomers have now detected six planets orbiting Gliese 581, the most known to circle any star beyond our own sun. [Space.com, 9/29/10]
- If There's Life on Alien Planet Gliese 581g, How Do We Find It?
- After spending decades searching for alien planets capable of harboring life, astronomers may have found one. So how can they check to see if life actually exists on this alien world? ... One of the planet's discoverers said in a briefing yesterday that "the chances of life on this planet are 100 percent." To determine if this is true, researchers will have to scrutinize Gliese 581g from afar, searching its atmosphere for certain telltale molecules. But it might be a while before they have the tools to do this properly. [Space.com, 9/30,10]
- Astronomer Seeks ET Machines
- If we ever do receive a message from outer space, we’ll want to know what kind of aliens sent it. SETI researcher Seth Shostak says we shouldn’t expect them to be anything like us – in fact, they might not be biological at all, but instead, extraterrestrial machines. [Astrobiology Magazine, 10/1/10]
- The Gates of Immortality
- Why do cells allow some mistakes to accumulate? If evolution is such a powerful process-one that finds solutions to all manner of problems-how could there be processes or problems that can't be fixed? [The Scientist, 10/1/10]
- The One True Path?
- Niswender and Galli are elucidating a molecular link between mental illness and problems with how the body processes sugars. That link is part of the complex series of events that make up the insulin-signaling pathway, a crucial mechanism by which the pancreatic hormone insulin directs the transport and storage of glucose in virtually every cell type in the body. This is only one of a recent rash of discoveries about how insulin is also intricately involved in many disease processes, including the growth of cancer cells and defects in bone mass regulation. [The Scientist, 10/1/10]
- A new source of CP violation?
- Abazov et al. report an unexpectedly large value of the same-sign dimuon charge asymmetry. This means that they see pairs of positive muons, μ+μ+, among the debris of their proton-antiproton collisions more often than they see pairs of negative muons, μ-μ-. The key point is that their measurement violates CP symmetry, which relates the behavior of matter and antimatter particles. [Physics, 8/16/10]
- Hagfish Analysis Opens Major Gap in Tree of Life
- Since the 1970s, many evolutionary biologists have considered an eel-like, deep-sea-dwelling creature called the hagfish to be the closest extant relative of a last common ancestor for all backboned creatures. That made the hagfish a stand-in for a transitional species between invertebrates and higher animals, spanning a leap as dramatic as any in evolutionary history. But a new family tree based on high-powered molecular analysis lumps hagfish together with lampreys, a jawless fish that’s primitive, but very much a vertebrate. [Wired, 10/19/10]
- On a quest to map the brain’s hidden territory
- On a recent morning, Wedeen pulled up images created with the new technology, in which the lakes of white were crisscrossed by colorful, ropy bundles of fibers, revealing an elegant, three-dimensional architecture. Looking more like art than anatomy, these strands form the connections in the brain — the “connectome.’’ They are neural highways crucial for brain function, including thoughts, movements, and sensations. [The Boston Globe, 10/11/10]
- The origin of complex life – it was all about energy
- According to a new hypothesis, put forward by Nick Lane and Bill Martin, we are all natural-born gas-guzzlers. Our very existence, and that of every animal, plant and fungus, depended on an ancient partnership, forged a few billion years ago, which gave our ancestors access to unparalleled supplies of energy and allowed them to escape from the shackles of simplicity. [Not Exactly Rocket Science, 10/20/10]
- The Fuel Of Evolution
- Within the cells of humans and all other modern creatures are lots of tiny mitochondria, which may have been the key to the evolution of complex multicellular life billions of years ago. [InsideScience.org, 10/22/10]
- Geologists revisit the Great Oxygenation Event
- Why did oxygen levels spike 2.5 billion years ago, and how much oxygen was there in the atmosphere really? Why are banded iron formations made of layers only a few centimeters thick, and why did they stop forming so abruptly? If the oceans were oxygenated 2.5 billion years ago, why did multicellular life delay its appearance for another 2 billion years? And did all these changes really take place at pretty much the same time everywhere on Earth? [Physorg.com, 8/19/10]
- Mirror Mirror On The Wall
- Every one of the four forces of Nature we know of - gravity, electromagnetism, the weak force, and the nuclear force - all originate from slight variations of this narrative. Gauge symmetries are the origins of all the forces of Nature. For example, gravity arises from a gauge symmetry in 3D: a sphere of a gauge with its hand pointing in any direction in the full three dimensional span of space. [Schrödinger's Dog, 10/22/10]
- Gravity Up Close
- Scientists know how gravity works at big distances -- the inter-planetary or inter-stellar range -- but does it work the same way at the inter-atomic range? A variety of tabletop experiments are trying to explore this issue. Already some theorists say that a departure from conventional gravity behavior could hint at the existence of extra dimensions. [InsideScience.org, 10/13/10]
- Cracks In The Universe
- Physicists are hot on the trail of one of strangest theorized structures in the universe. A team of researchers have announced what they think are the first indirect observations of ancient cosmic strings, bizarre objects thought to have contributed to the arrangement of objects throughout the universe. [InsideScience.org, 10/11/10]
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Young stars biting the cloud that feeds them
Young stars biting the cloud that feeds them (8/30/10)
NGC 604 – click for 1280×919 image
A billowing cloud of hydrogen in the Triangulum galaxy (Messier 33), about 2.7 million light-years away from Earth, glows with the energy released by hundreds of young, bright stars. This NASA/ESA Hubble Spare Telescope image provides the sharpest view of NGC 604 so far obtained.
Some 1500 light-years across, this is one of the largest, brightest concentrations of ionised hydrogen (H II) in our local group of galaxies, and is a major centre of star formation.
The gas in NGC 604, around nine tenths of it hydrogen, is gradually collapsing under the force of gravity to create new stars. Once these stars have formed, the vigorous ultraviolet radiation they emit excites the remaining gas in the cloud, making it glow a distinct shade of red. This colour is typical not only of NGC 604 but of other H II regions too.
NGC 604 – click for 1280×919 image
Alexander McQueen
source: unknown
I remember when Alexander McQueen passed away a reader had approached me asking for me to post up pictures of him and his tattoos. I failed to do so at the time because I couldn't find any good pictures of his tattoos.But I think this picture of a tattoo of one of his creations is perfect.
It's a tattoo of this:
What activates a supermassive black hole?
There's good evidence that massive black holes exist at the centers of most large galaxies having a central bulge, and even within galaxies that lack a central bulge, are small, or have an irregular form. Such black holes can range in size up to more than 10 billion solar masses (M⊙). Little is known about what the average or typical mass of a central black hole is, although most are probably a lot smaller, such as that of Sagittarius A* in our galaxy, which is only ~4.2×106 M⊙.
Four million solar masses is still pretty hefty, so such objects are usually called supermassive black holes (SMBHs), as opposed to black holes that form as supernova remnants and are only at most a few M⊙. It's not known exactly how SMBHs form and evolve. One clue is that most seem to reside in non-dwarf galaxies with a regular shape and a noticeable central bulge. This suggests that SMBHs form and evolve in tandem with the bulge. However, there are exceptions, such as one discussed here: Supermassive black hole in a dwarf galaxy. Another survey of small (under 1010 M⊙) inactive galaxies in the Virgo cluster found that at least 24% had an X-ray-emitting SMBH.
Since a black hole emits little or no radiation directly, even SMBHs are difficult to detect at distances of millions of light years, unless they are surrounded by a substantial amount of gas and dust that is heated enough in the process of falling into the SMBH that it can strongly emit radiation on its own or produce other detectable effects, like jets. Objects that fall in this category are active galactic nuclei (AGN). In most cases only SMBHs that are active as AGNs are readily detectable, so these are the only specimens we know much at all about.
I've discussed AGN a lot, most recently here, here, here, here, here.
In order to study how SMBHs form and evolve we pretty much have to rely on studies of AGNs, which can provide many clues about this issue. Unfortunately, we don't know much about what causes a relatively quiescent SMBH to become active and turn into an AGN. It's this latter question that's addressed, indirectly, by the research to be discussed here.
But first let's back up to SMBHs in general. There are several interrelated questions concerning their origin and evolution. What accounts for their formation and periods of rapid growth? Do they form before, after, or in parallel with the formation of the galaxies in which they reside? What stimulates their intense outbursts of energy as AGNs or quasars?
The most basic question is: What are the typical ways that SMBHs grow? Possible answers include merger between smaller SMBHs, slow but steady accretion of matter from the surrounding galaxy, or bursts of rapid accretion when substantial amounts of gas and dust are swept up by the SMBH.
Each of these questions, among others, stimulates intense debates among astrophysicists who study such things. These questions are interesting and important not just for their own sake. Since there is a lot of evidence that the evolution of a galaxy and of its central SMBH occur in tandem, understanding the evolution of the SMBH helps us understand that of the whole galaxy.
The research we're concerned with here was designed to study the question by surveying a large number of galaxies that can be examined in some detail because they are not too distant. In this case, that means having a redshift z≤1. That corresponds to a distance (measured in light travel time) of about 7.7 billion light years – a little more than half the size of the visible universe. Since the research needs to examine the visible form of the object, anything farther away is too distant for even the Hubble telescope to resolve in sufficient detail. Also, at z=1 all light from the visible part of the spectrum is shifted to infrared, which Hubble's optics aren't optimized for.
An AGN produces quite energetic radiation across most of the electromagnetic spectrum. So, at least in most cases, it is a sign of the rapid burst model of growth mentioned above. This is typically just a relatively short phase in the life of the galaxy-black hole combination – on the order of a hundred million years or so. That's based on the observation that only about 1% (very roughly) of large galaxies are in this phase, over the 13.7-billion year age of the visible universe. Whether this represents the only mode of growth, or even the bulk of it, is the big unknown. And of course, if there are SMBHs that grow by modes other than rapid accretion, we won't even detect them as AGN.
The standard model of AGNs, which is pretty well accepted by the astrophysical community, is that rapid accretion of interstellar gas and dust around a SMBH is what powers the AGN's "engine". Presumably, then, the AGN goes quiet when most of the available gas and dust has been consumed. But that leaves the question of what initiates the process in the first place. Since there are still many AGNs that are active in the universe out to z=1, so that the galaxies involved have been growing for at least 5 billion years since the early days of the universe, AGNs could not have been active for their entire lives. Therefore, something happened at some point to trigger the activity we observe now.
Astrophysicists want to know what that something is. At least initially, there is much more gas and dust spread throughout the galaxy than in the center. Something has to happen to cause that matter to lose its angular momentum so it can fall into the center. One popular hypothesis has been that this process is triggered by mergers between mature galaxies of roughly equal size, as the gas and dust perturbed by the merger falls inward and is swept up by the central black holes (which might merge themselves). Up until now, there has not been a large-scale investigation of this hypothesis.
Now we have one: The bulk of the black hole growth since z~1 occurs in a secular universe: No major merger-AGN connection. (Available at the arXiv: 1009.3265v2.)
A sample of 140 AGNs was selected for examination. Another sample of 1264 inactive galaxies, carefully matched in size, distance, etc. was also selected for comparison. The only reliable indication of an ongoing merger is a visible distortion of the object's shape, so this is taken as a proxy for the occurrence of a merger. However, the galaxies observed could be undergoing "minor" mergers that don't result in visible distortion (considering how far away most selected objects are). And on the other hand, there's no way to be sure that an object's observable distortion is due to a merger. So the conservative view is that this research is looking at the correlation between galaxy activity and distortion of shape.
There are two specific questions addressed by the research: (1) How many AGN have a distorted structure that appears to be the result of a galactic merger? (2) Do AGNs show any significant difference in terms of visible distortion from otherwise comparable inactive galaxies?
The first question is about whether mergers that produce distortions are a necessary condition for an AGN. Since fewer than 15% of AGNs have visible distortion, the answer is clearly "no". The second question concerns whether a merger that produces distortion is sufficient to trigger an AGN. Since there was no significant difference between AGNs and a control set of non-AGNs in terms of frequency of visible distortion, it seems that whatever causes a distorted form (such as a merger) is not a significant cause for triggering an AGN.
Bottom line: Not only are distortion-producing mergers unnecessary for triggering an AGN, they do not even seem to be a significant cause. One way to think of it is as a visible symptom of some underlying process that might otherwise be hard to detect. (A medical example would be a cancer, whose presence might be indicated by physical symptoms or biochemical markers in the blood.) In the present case, it appears that having a distorted form isn't a symptom usually exhibited by a galaxy when an AGN is present - and in fact, it doesn't predict the presence of an AGN at all.
It is important to be able to identify reliable symptoms, because a galaxy may have an AGN that is not readily detectable directly. Many AGNs are not intense radio sources, presumably because they do not have significant jet structures. And unless we are viewing the galaxy more or less face-on, radiation at shorter wavelengths can be blocked by a thick torus of gas and dust surrounding the central engine of the AGN.
Not all important questions are answered by this study. For example, galaxy mergers that do not significantly distort galactic structure – perhaps involving the cannibalism of a small galaxy by a large one – might play an important role in triggering an AGN.
The results of this research are surprising, because they seem to rule out distortion-producing galaxy mergers as an important cause of AGNs – the previous general assumption. However, it shouldn't be concluded that galaxy collisions can never produce AGNs, let alone SMBHs. There is still the question of whether a SMBH can form "from scratch" without some sort of "seed". It could be that very large black holes formed in the very first instants after the big bang, as "primordial" black holes. (See here, for example. Further possibility for the formation of seed black holes are discussed here.)
However, a simulation study reported last year in Nature (here) showed that in the early universe, SMBHs could form directly from galaxy collisions. But conditions at that time were very different – there was much more gas around that hadn't formed into stars, and a much larger single mass of gas could accumulate without forming stars. Time permitting, as usual, I'd like to discuss this research in another post.
Further reading:
Four million solar masses is still pretty hefty, so such objects are usually called supermassive black holes (SMBHs), as opposed to black holes that form as supernova remnants and are only at most a few M⊙. It's not known exactly how SMBHs form and evolve. One clue is that most seem to reside in non-dwarf galaxies with a regular shape and a noticeable central bulge. This suggests that SMBHs form and evolve in tandem with the bulge. However, there are exceptions, such as one discussed here: Supermassive black hole in a dwarf galaxy. Another survey of small (under 1010 M⊙) inactive galaxies in the Virgo cluster found that at least 24% had an X-ray-emitting SMBH.
Since a black hole emits little or no radiation directly, even SMBHs are difficult to detect at distances of millions of light years, unless they are surrounded by a substantial amount of gas and dust that is heated enough in the process of falling into the SMBH that it can strongly emit radiation on its own or produce other detectable effects, like jets. Objects that fall in this category are active galactic nuclei (AGN). In most cases only SMBHs that are active as AGNs are readily detectable, so these are the only specimens we know much at all about.
I've discussed AGN a lot, most recently here, here, here, here, here.
In order to study how SMBHs form and evolve we pretty much have to rely on studies of AGNs, which can provide many clues about this issue. Unfortunately, we don't know much about what causes a relatively quiescent SMBH to become active and turn into an AGN. It's this latter question that's addressed, indirectly, by the research to be discussed here.
But first let's back up to SMBHs in general. There are several interrelated questions concerning their origin and evolution. What accounts for their formation and periods of rapid growth? Do they form before, after, or in parallel with the formation of the galaxies in which they reside? What stimulates their intense outbursts of energy as AGNs or quasars?
The most basic question is: What are the typical ways that SMBHs grow? Possible answers include merger between smaller SMBHs, slow but steady accretion of matter from the surrounding galaxy, or bursts of rapid accretion when substantial amounts of gas and dust are swept up by the SMBH.
Each of these questions, among others, stimulates intense debates among astrophysicists who study such things. These questions are interesting and important not just for their own sake. Since there is a lot of evidence that the evolution of a galaxy and of its central SMBH occur in tandem, understanding the evolution of the SMBH helps us understand that of the whole galaxy.
The research we're concerned with here was designed to study the question by surveying a large number of galaxies that can be examined in some detail because they are not too distant. In this case, that means having a redshift z≤1. That corresponds to a distance (measured in light travel time) of about 7.7 billion light years – a little more than half the size of the visible universe. Since the research needs to examine the visible form of the object, anything farther away is too distant for even the Hubble telescope to resolve in sufficient detail. Also, at z=1 all light from the visible part of the spectrum is shifted to infrared, which Hubble's optics aren't optimized for.
An AGN produces quite energetic radiation across most of the electromagnetic spectrum. So, at least in most cases, it is a sign of the rapid burst model of growth mentioned above. This is typically just a relatively short phase in the life of the galaxy-black hole combination – on the order of a hundred million years or so. That's based on the observation that only about 1% (very roughly) of large galaxies are in this phase, over the 13.7-billion year age of the visible universe. Whether this represents the only mode of growth, or even the bulk of it, is the big unknown. And of course, if there are SMBHs that grow by modes other than rapid accretion, we won't even detect them as AGN.
The standard model of AGNs, which is pretty well accepted by the astrophysical community, is that rapid accretion of interstellar gas and dust around a SMBH is what powers the AGN's "engine". Presumably, then, the AGN goes quiet when most of the available gas and dust has been consumed. But that leaves the question of what initiates the process in the first place. Since there are still many AGNs that are active in the universe out to z=1, so that the galaxies involved have been growing for at least 5 billion years since the early days of the universe, AGNs could not have been active for their entire lives. Therefore, something happened at some point to trigger the activity we observe now.
Astrophysicists want to know what that something is. At least initially, there is much more gas and dust spread throughout the galaxy than in the center. Something has to happen to cause that matter to lose its angular momentum so it can fall into the center. One popular hypothesis has been that this process is triggered by mergers between mature galaxies of roughly equal size, as the gas and dust perturbed by the merger falls inward and is swept up by the central black holes (which might merge themselves). Up until now, there has not been a large-scale investigation of this hypothesis.
Now we have one: The bulk of the black hole growth since z~1 occurs in a secular universe: No major merger-AGN connection. (Available at the arXiv: 1009.3265v2.)
A sample of 140 AGNs was selected for examination. Another sample of 1264 inactive galaxies, carefully matched in size, distance, etc. was also selected for comparison. The only reliable indication of an ongoing merger is a visible distortion of the object's shape, so this is taken as a proxy for the occurrence of a merger. However, the galaxies observed could be undergoing "minor" mergers that don't result in visible distortion (considering how far away most selected objects are). And on the other hand, there's no way to be sure that an object's observable distortion is due to a merger. So the conservative view is that this research is looking at the correlation between galaxy activity and distortion of shape.
There are two specific questions addressed by the research: (1) How many AGN have a distorted structure that appears to be the result of a galactic merger? (2) Do AGNs show any significant difference in terms of visible distortion from otherwise comparable inactive galaxies?
The first question is about whether mergers that produce distortions are a necessary condition for an AGN. Since fewer than 15% of AGNs have visible distortion, the answer is clearly "no". The second question concerns whether a merger that produces distortion is sufficient to trigger an AGN. Since there was no significant difference between AGNs and a control set of non-AGNs in terms of frequency of visible distortion, it seems that whatever causes a distorted form (such as a merger) is not a significant cause for triggering an AGN.
Bottom line: Not only are distortion-producing mergers unnecessary for triggering an AGN, they do not even seem to be a significant cause. One way to think of it is as a visible symptom of some underlying process that might otherwise be hard to detect. (A medical example would be a cancer, whose presence might be indicated by physical symptoms or biochemical markers in the blood.) In the present case, it appears that having a distorted form isn't a symptom usually exhibited by a galaxy when an AGN is present - and in fact, it doesn't predict the presence of an AGN at all.
It is important to be able to identify reliable symptoms, because a galaxy may have an AGN that is not readily detectable directly. Many AGNs are not intense radio sources, presumably because they do not have significant jet structures. And unless we are viewing the galaxy more or less face-on, radiation at shorter wavelengths can be blocked by a thick torus of gas and dust surrounding the central engine of the AGN.
Not all important questions are answered by this study. For example, galaxy mergers that do not significantly distort galactic structure – perhaps involving the cannibalism of a small galaxy by a large one – might play an important role in triggering an AGN.
The results of this research are surprising, because they seem to rule out distortion-producing galaxy mergers as an important cause of AGNs – the previous general assumption. However, it shouldn't be concluded that galaxy collisions can never produce AGNs, let alone SMBHs. There is still the question of whether a SMBH can form "from scratch" without some sort of "seed". It could be that very large black holes formed in the very first instants after the big bang, as "primordial" black holes. (See here, for example. Further possibility for the formation of seed black holes are discussed here.)
However, a simulation study reported last year in Nature (here) showed that in the early universe, SMBHs could form directly from galaxy collisions. But conditions at that time were very different – there was much more gas around that hadn't formed into stars, and a much larger single mass of gas could accumulate without forming stars. Time permitting, as usual, I'd like to discuss this research in another post.
 | Cisternas, M., Jahnke, K., Inskip, K., Kartaltepe, J., Koekemoer, A., Lisker, T., Robaina, A., Scodeggio, M., Sheth, K., Trump, J., Andrae, R., Miyaji, T., Lusso, E., Brusa, M., Capak, P., Cappelluti, N., Civano, F., Ilbert, O., Impey, C., Leauthaud, A., Lilly, S., Salvato, M., Scoville, N., & Taniguchi, Y. (2011). THE BULK OF THE BLACK HOLE GROWTH SINCE Z~1 OCCURS IN A SECULAR UNIVERSE: NO MAJOR MERGER-AGN CONNECTION The Astrophysical Journal, 726 (2) DOI: 10.1088/0004-637X/726/2/57 |
Further reading:
- Galaxy collisions may not fuel black holes after all (1/6/11)
- Mystery Deepens in Origin of Violent Black Holes (1/5/11)
- Galactic Smashups Leave Giant Black Holes Hungry (1/5/11)
- Study: Hyperactive Black Holes Aren’t Caused by Galactic Smash-ups (1/6/11)
- Collisions Cleared as Cause of Galactic Infernos (1/5/11)
- Identity parade clears cosmic collisions of the suspicion of promoting black hole growth (1/5/11)
Testing the Fountain of Youth in the lab
It's been more than 10 years since it was noticed that certain enzymes – the sirtuins – had life-extending properties in organisms like yeast, and later nematodes, fruit flies, and mice. The excitement spread to other compounds, such as resveratrol, that seemed to activate or assist sirtuins. Hopes were high that such things might offer the known longevity benefits of calorie restriction in a pill form. Ever since then the gold rush has been on to figure out how these things work – and if possible, to be the first to market with the Fountain of Youth in a bottle.
We've discussed sirtuins here a number of times before – here's a list of some of those discussions. If you need to brush up on the background, those would be good places to start.
The initial sirtuin that seemed to be most important for the longevity of yeast was SIR2. The gene for SIR2 is highly conserved in evolution – so it's probably kind of important. Homologs of SIR2 have been found in many sorts of higher organisms (nematodes, fruit flies, etc.). In mammals, including humans, there is a whole family of sirtuins, having at least 7 members, named SIRTx for x=1 to 7. ("SIRT" and "sirtuin" refer to SIR-two, where SIR was an acronym for "silent information regulator".)
SIR2 is primarily a histone deacetylase (HDAC), that is, an enzyme that removes acetyl groups from histone proteins (and often other types of proteins as well). Histones are the building block proteins that make up nucleosomes, around which DNA is spooled in chromosomes. Normally, DNA is tightly bound to the histones, which prevents the genes in the tightly bound portion of DNA from being transcribed into RNA in order to make proteins. In other words, the genes bound to a histone are effectively silenced. In order for a gene to be expressed, the histone closest to the portion of DNA containing the gene has to have an acetyl group attached at an appropriate location. Enzymes ("acetyltransferases") attach acetyl groups (in the process called acetylation) to histones in order to allow gene expression. Consequently, deacetylase enzymes, such as several sirtuins, are able to silence genes by removing acetyl groups from histones.
SIRT1 is the most intensively studied mammalian sirtuin. Like SIR2, it is primarily a histone deacetylase that is active in a cell nucleus to silence a wide variety of genes. Since SIRT1 can silence a large number of genes, it affects many cellular processes. However, there is one additional complication. SIR2 and SIRT1 only have their deacetylation ability in the presence of a small molecule called NAD: nicotinamide adenine dinucleotide, and only when NAD has a net positive charge, due to the loss of one electron during the process of metabolism in which cells generate needed energy. NAD+ denotes this form of NAD. (The neutral form of NAD is denoted by NADH.) Because of the role of NAD+, SIR2 is said to be a "NAD+-dependent" histone deacetylase.
All this is important, because research over the past 10+ years has shown that the lifespan-extending properties of calorie restriction, especially in simple organisms like yeast and nematodes, seem to be related, at least sometimes, with the deacetylation properties of SIR2 in the presence of NAD+. When an organism is in a calorie restricted environment, metabolism slows down, and less NAD+ gets used up. As a result, there is more NAD+ around. So SIR2 is more effective. So genes are silenced that would otherwise be expressed. Silencing these genes seem to help an organism live longer when nourishment is not ample – so that it can survive until the buffet table is restocked.
In an organism on a normal (not calorie restricted) diet, up-regulating SIR2 or otherwise enhancing its gene-silencing abilities seems to compensate for decreased amounts of NAD+, and thereby achieves for the organism some of the anti-aging benefits of a calorie-restricted diet without having to go hungry.
The problem is that the expression of so many different genes can be affected by SIR2 deacetylation that it's difficult to identify which genes among these are actually useful for promoting longevity or retarding aging – especially in organisms more complex than yeast or nematodes.
Now, however, research has come out involving a much less studied mammalian sirtuin, SIRT3 – Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction. (I recommend viewing this link, since the illustration on the page will be helpful in understanding what follows here.) In spite of caveats I'll mention toward the end, this is a very significant and well-done piece of research.
A number of properties of SIRT3 had already been observed prior to this latest research. It is, like SIRT1, also a NAD+-dependent deacetylase enzyme. But unlike SIRT1, its main activity is found in cell mitochondria instead of in the nucleus. Consequently, SIRT3 deacetylates mitochondrial proteins instead of histones.
Of particular interest, this SIRT3 activity was known to be associated with calorie restriction (CR), because of overexpression in CR conditions and presumably also because of the NAD+-dependence. For example, studies in mice have shown that CR increases SIRT3 expression in liver mitochondria. Further, in knockout mice without SIRT3 mitochondrial fatty acid oxidation problems are found. Under CR SIRT3 is also overexpressed in mouse heart cells and may protect these cells from oxidative stress-induced cell death. (However, in this case it's possible that the effect resulted from HDAC activity in the cell nucleus.) So SIRT3 seems to be associated with anti-oxidant activity. There is, additionally, mechanistic evidence that SIRT3 inhibits mitochondria-related carcinogenesis. For instance, knockout mice without SIRT3 are susceptible to breast tumors.
The latest research presents strong evidence that under calorie restriction SIRT3 is involved in suppressing oxidative damage. The evidence is based on studies of oxidative stress-induced cochlear cell death responsible for age-related hearing loss (AHL) in mice. AHL is a pretty typical example of health problems associated with aging – one that affects humans as well as mice. The research not only shows an association between SIRT3 and protection from oxidative damage, but goes deep into the apparent mechanism involved. A variety of different in vitro and in vivo experiments with knockout mice provide the evidence.
To begin with, at the highest level, the researchers found that SIRT3 is required along with CR to inhibit age-related cochlear cell death and hearing loss. The knockout mice used in this, and other in vivo experiments, had both copies of the SIRT3 gene knocked out. The rate of progression of AHL was first measured in wild type (WT) mice as controls. CR was found to delay or mitigate AHL in the controls – but not in the knockout mice. This implies SIRT3 is necessary for CR to inhibit the progression of AHL – there's no benefit of CR for this condition without SIRT3. Further, when the cochlear cells of the experimental mice were examined, it was found that CR retarded cell death in the control animals but not in the mice without SIRT3.
So the key process to be concerned with is progressive cell death related to aging. The next experiments showed that the cell death was the result of oxidative damage. A lot of other studies have shown that CR inhibits oxidative damage to DNA, proteins, and lipids in many types of mammalian tissues. In the present research this was confirmed by examination of DNA in cochlear, brain, and liver tissues of control mice. But CR did not inhibit oxidative damage in the same tissues of the knockout mice. So SIRT3 appears to be necessary for the inhibition of oxidative damage to DNA, which presumably was responsible for accelerated cell death.
The next issue needing to be addressed is the mechanism by which CR inhibits oxidative damage. It is known that a small molecule, glutathione, is the major small molecule antioxidant in cells. Glutathione can exist in two oxidation states – reduced (GSH) or oxidized (GSSG). A high ratio of GSH to GSSG protects other molecules in the cell from oxidative damage, and GSH predominates in the healthy mitochondria of young mice. Conversely, a low ratio of GSH to GSSG is a marker for oxidative stress and/or aging. In the present research, the GSH:GSSG ratio was tested in control and knockout mice under CR conditions, at the age of 5 months. In the mitochondria of inner ear cells, as well as in brain and liver cells, it was found that the GSH:GSSG ratio increased as a result of CR in control mice, but not in knockout mice. Once again the presence of SIRT3 was shown to be necessary for an effect.
Obviously, the next thing to look at is how the GSH:GSSG ratio is controlled. The enzyme glutathione reductase (GSR) is known to be responsible for converting GSSG to GSH. So what happens is that reactive oxygen species (ROS) get soaked up in converting GSH to GSSG, and GSR reverses this to convert GSSG back to GSH.
However, in order to work GSR requires another molecule, nicotinamide adenine dinucleotide phosphate (NADPH) to do its job. NADPH is nothing but NAD, which we encountered in connection with the HDAC function of SIRT1, with a phosphate group attached. Like NAD, NADPH also exists in an oxidized form, NADPH+. This latter molecule predominates in mitochondria, and needs to be converted back to NADPH for use by GSR. (All this activity is really just shuffling electrons from one place to another. The pairs of molecules that mediate the activity are called "redox couples".)
So, what is it that converts NADPH+ to the plain old NADPH that we need? Well, that task is handled by yet another mitochondrial enzyme, isocitrate dehydrogenase 2 (Idh2). Don't despair – this is the last step! There is just one wrinkle. Idh2 is normally found in an acetylated form, in which case it is inactive. It needs to be deacetylated in order to become active and convert NADPH+ to NADPH. And that is precisely where the deacetylation function of SIRT3 comes into play. The researchers hypothesized that SIRT3 was needed in order to activate Idh2.
In order to test the hypothesis, they first measured acetylation of Idh2 in the control mice, with both normal and CR diets. With a normal diet, acetylation of Idh2 was substantial, but with CR there was an 8-fold decrease of acetylation. So it only remains to find the reason for that. In knockout mice, with no SIRT3, acetylation of Idh2 was "robust" with both normal and CR diets. That's a pretty good indication that SIRT3 was required for the effect. As a further indication, SIRT3 levels in the control mice were 3 times as high with a CR diet compared to a normal diet.
So SIRT3 is necessary for deacetylation of Idh2 under CR conditions, but there's still the possibility that it isn't sufficient by itself. It's possible that CR has other effects that facilitate deacetylation – CR may cause expression or activation of other enzymes that are needed. It's also possible that CR has other effects that increase NADPH independently of Idh2.
What if NADPH levels were tested directly? It was found that in the control mice NADPH did increase in all tissue types tested when a CR diet replaced a normal one, but this effect was not found in the knockout mice.
Efforts were made to use biochemical experiments (in vitro) to determine whether SIRT3 alone is responsible for deacetylating Idh2 under CR conditions. For example, another sirtuin, SIRT5, is also a deacetylase that occurs in mitochondria. Could it be helping deacetylate Idh2? The biochemical experiments indicated this was not the case.
Unsurprisingly, both normal and knockout mice were found to be leaner when fed a CR diet. Is it possible that lower body mass, especially resulting from less fat tissue, had some role in the protection from oxidative damage resulting from a CR diet? Perhaps, but other factors like that certainly weren't sufficient, as it was pretty clear that SIRT3 (absent in the knockout mice) was necessary, at least as far as AHL is concerned. It's still possible that SIRT3 isn't necessary for anti-aging effects of CR in tissue types that weren't tested (i. e. other than inner ear, brain, and liver tissue), or in mammals other than mice. The case is pretty solid for AHL in mice, but obviously there are many other age-related conditions and other species that should be investigated.
I should apologize for all the biochemical details presented here, but at least they should give you a good indication of just how complicated the effects of CR on aging and longevity can be – and probably are. There's a whole lot of work yet to be done before a reliable anti-aging pill can be developed for humans. Enthusiastic claims that this research "could lead to" therapies to slow down aging in general are basically BS. Yeah, these findings will help, but a heck of a lot more will be needed as well.
(As an example of just how badly misleading journalists who write about this stuff can be, consider this report, which begins with the claim: "In a remarkable demonstration of the ability of calorie restriction to blunt the effects of aging, scientists at the University of Wisconsin-Madison have succeeded in delaying age-related hearing loss in mice." Although the research showed that calorie restriction can do this, it did not produce any new way to do it. Instead, it shows how CR probably works by showing how CR doesn't work if SIRT3 is absent.)
So what's the bottom line here? It's pretty clear from this and many other studies that oxidative damage in cells is a cause of cell death and therefore of various health problems associated with aging. Undoubtedly there are a number of other factors that contribute to aging-related problems, such as cell death due to other causes and weakening or disregulation of the immune system. And even in the case of oxidative damage, there are many ways it can come about, and also many ways it might be inhibited. If you think of aging as a complex disease, like cancer – a point of view that has its detractors – then there are bound to be many causes and contributing factors. And also many ways to inhibit or arrest the process. The example considered here is just one of many.
Further reading:
Scientists ferret out a key pathway for aging (11/18/10)
Calorie restriction delays age-related hearing loss, UW study finds (11/18/10)
Scientists ID key protein that links dietary restriction with healthy hearing, aging (12/16/10)
Calorie Restrictions Slow Aging by Enzyme Pathway (11/19/10)
We've discussed sirtuins here a number of times before – here's a list of some of those discussions. If you need to brush up on the background, those would be good places to start.
The initial sirtuin that seemed to be most important for the longevity of yeast was SIR2. The gene for SIR2 is highly conserved in evolution – so it's probably kind of important. Homologs of SIR2 have been found in many sorts of higher organisms (nematodes, fruit flies, etc.). In mammals, including humans, there is a whole family of sirtuins, having at least 7 members, named SIRTx for x=1 to 7. ("SIRT" and "sirtuin" refer to SIR-two, where SIR was an acronym for "silent information regulator".)
SIR2 is primarily a histone deacetylase (HDAC), that is, an enzyme that removes acetyl groups from histone proteins (and often other types of proteins as well). Histones are the building block proteins that make up nucleosomes, around which DNA is spooled in chromosomes. Normally, DNA is tightly bound to the histones, which prevents the genes in the tightly bound portion of DNA from being transcribed into RNA in order to make proteins. In other words, the genes bound to a histone are effectively silenced. In order for a gene to be expressed, the histone closest to the portion of DNA containing the gene has to have an acetyl group attached at an appropriate location. Enzymes ("acetyltransferases") attach acetyl groups (in the process called acetylation) to histones in order to allow gene expression. Consequently, deacetylase enzymes, such as several sirtuins, are able to silence genes by removing acetyl groups from histones.
SIRT1 is the most intensively studied mammalian sirtuin. Like SIR2, it is primarily a histone deacetylase that is active in a cell nucleus to silence a wide variety of genes. Since SIRT1 can silence a large number of genes, it affects many cellular processes. However, there is one additional complication. SIR2 and SIRT1 only have their deacetylation ability in the presence of a small molecule called NAD: nicotinamide adenine dinucleotide, and only when NAD has a net positive charge, due to the loss of one electron during the process of metabolism in which cells generate needed energy. NAD+ denotes this form of NAD. (The neutral form of NAD is denoted by NADH.) Because of the role of NAD+, SIR2 is said to be a "NAD+-dependent" histone deacetylase.
All this is important, because research over the past 10+ years has shown that the lifespan-extending properties of calorie restriction, especially in simple organisms like yeast and nematodes, seem to be related, at least sometimes, with the deacetylation properties of SIR2 in the presence of NAD+. When an organism is in a calorie restricted environment, metabolism slows down, and less NAD+ gets used up. As a result, there is more NAD+ around. So SIR2 is more effective. So genes are silenced that would otherwise be expressed. Silencing these genes seem to help an organism live longer when nourishment is not ample – so that it can survive until the buffet table is restocked.
In an organism on a normal (not calorie restricted) diet, up-regulating SIR2 or otherwise enhancing its gene-silencing abilities seems to compensate for decreased amounts of NAD+, and thereby achieves for the organism some of the anti-aging benefits of a calorie-restricted diet without having to go hungry.
The problem is that the expression of so many different genes can be affected by SIR2 deacetylation that it's difficult to identify which genes among these are actually useful for promoting longevity or retarding aging – especially in organisms more complex than yeast or nematodes.
Now, however, research has come out involving a much less studied mammalian sirtuin, SIRT3 – Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction. (I recommend viewing this link, since the illustration on the page will be helpful in understanding what follows here.) In spite of caveats I'll mention toward the end, this is a very significant and well-done piece of research.
A number of properties of SIRT3 had already been observed prior to this latest research. It is, like SIRT1, also a NAD+-dependent deacetylase enzyme. But unlike SIRT1, its main activity is found in cell mitochondria instead of in the nucleus. Consequently, SIRT3 deacetylates mitochondrial proteins instead of histones.
Of particular interest, this SIRT3 activity was known to be associated with calorie restriction (CR), because of overexpression in CR conditions and presumably also because of the NAD+-dependence. For example, studies in mice have shown that CR increases SIRT3 expression in liver mitochondria. Further, in knockout mice without SIRT3 mitochondrial fatty acid oxidation problems are found. Under CR SIRT3 is also overexpressed in mouse heart cells and may protect these cells from oxidative stress-induced cell death. (However, in this case it's possible that the effect resulted from HDAC activity in the cell nucleus.) So SIRT3 seems to be associated with anti-oxidant activity. There is, additionally, mechanistic evidence that SIRT3 inhibits mitochondria-related carcinogenesis. For instance, knockout mice without SIRT3 are susceptible to breast tumors.
The latest research presents strong evidence that under calorie restriction SIRT3 is involved in suppressing oxidative damage. The evidence is based on studies of oxidative stress-induced cochlear cell death responsible for age-related hearing loss (AHL) in mice. AHL is a pretty typical example of health problems associated with aging – one that affects humans as well as mice. The research not only shows an association between SIRT3 and protection from oxidative damage, but goes deep into the apparent mechanism involved. A variety of different in vitro and in vivo experiments with knockout mice provide the evidence.
To begin with, at the highest level, the researchers found that SIRT3 is required along with CR to inhibit age-related cochlear cell death and hearing loss. The knockout mice used in this, and other in vivo experiments, had both copies of the SIRT3 gene knocked out. The rate of progression of AHL was first measured in wild type (WT) mice as controls. CR was found to delay or mitigate AHL in the controls – but not in the knockout mice. This implies SIRT3 is necessary for CR to inhibit the progression of AHL – there's no benefit of CR for this condition without SIRT3. Further, when the cochlear cells of the experimental mice were examined, it was found that CR retarded cell death in the control animals but not in the mice without SIRT3.
So the key process to be concerned with is progressive cell death related to aging. The next experiments showed that the cell death was the result of oxidative damage. A lot of other studies have shown that CR inhibits oxidative damage to DNA, proteins, and lipids in many types of mammalian tissues. In the present research this was confirmed by examination of DNA in cochlear, brain, and liver tissues of control mice. But CR did not inhibit oxidative damage in the same tissues of the knockout mice. So SIRT3 appears to be necessary for the inhibition of oxidative damage to DNA, which presumably was responsible for accelerated cell death.
The next issue needing to be addressed is the mechanism by which CR inhibits oxidative damage. It is known that a small molecule, glutathione, is the major small molecule antioxidant in cells. Glutathione can exist in two oxidation states – reduced (GSH) or oxidized (GSSG). A high ratio of GSH to GSSG protects other molecules in the cell from oxidative damage, and GSH predominates in the healthy mitochondria of young mice. Conversely, a low ratio of GSH to GSSG is a marker for oxidative stress and/or aging. In the present research, the GSH:GSSG ratio was tested in control and knockout mice under CR conditions, at the age of 5 months. In the mitochondria of inner ear cells, as well as in brain and liver cells, it was found that the GSH:GSSG ratio increased as a result of CR in control mice, but not in knockout mice. Once again the presence of SIRT3 was shown to be necessary for an effect.
Obviously, the next thing to look at is how the GSH:GSSG ratio is controlled. The enzyme glutathione reductase (GSR) is known to be responsible for converting GSSG to GSH. So what happens is that reactive oxygen species (ROS) get soaked up in converting GSH to GSSG, and GSR reverses this to convert GSSG back to GSH.
However, in order to work GSR requires another molecule, nicotinamide adenine dinucleotide phosphate (NADPH) to do its job. NADPH is nothing but NAD, which we encountered in connection with the HDAC function of SIRT1, with a phosphate group attached. Like NAD, NADPH also exists in an oxidized form, NADPH+. This latter molecule predominates in mitochondria, and needs to be converted back to NADPH for use by GSR. (All this activity is really just shuffling electrons from one place to another. The pairs of molecules that mediate the activity are called "redox couples".)
So, what is it that converts NADPH+ to the plain old NADPH that we need? Well, that task is handled by yet another mitochondrial enzyme, isocitrate dehydrogenase 2 (Idh2). Don't despair – this is the last step! There is just one wrinkle. Idh2 is normally found in an acetylated form, in which case it is inactive. It needs to be deacetylated in order to become active and convert NADPH+ to NADPH. And that is precisely where the deacetylation function of SIRT3 comes into play. The researchers hypothesized that SIRT3 was needed in order to activate Idh2.
In order to test the hypothesis, they first measured acetylation of Idh2 in the control mice, with both normal and CR diets. With a normal diet, acetylation of Idh2 was substantial, but with CR there was an 8-fold decrease of acetylation. So it only remains to find the reason for that. In knockout mice, with no SIRT3, acetylation of Idh2 was "robust" with both normal and CR diets. That's a pretty good indication that SIRT3 was required for the effect. As a further indication, SIRT3 levels in the control mice were 3 times as high with a CR diet compared to a normal diet.
So SIRT3 is necessary for deacetylation of Idh2 under CR conditions, but there's still the possibility that it isn't sufficient by itself. It's possible that CR has other effects that facilitate deacetylation – CR may cause expression or activation of other enzymes that are needed. It's also possible that CR has other effects that increase NADPH independently of Idh2.
What if NADPH levels were tested directly? It was found that in the control mice NADPH did increase in all tissue types tested when a CR diet replaced a normal one, but this effect was not found in the knockout mice.
Efforts were made to use biochemical experiments (in vitro) to determine whether SIRT3 alone is responsible for deacetylating Idh2 under CR conditions. For example, another sirtuin, SIRT5, is also a deacetylase that occurs in mitochondria. Could it be helping deacetylate Idh2? The biochemical experiments indicated this was not the case.
Unsurprisingly, both normal and knockout mice were found to be leaner when fed a CR diet. Is it possible that lower body mass, especially resulting from less fat tissue, had some role in the protection from oxidative damage resulting from a CR diet? Perhaps, but other factors like that certainly weren't sufficient, as it was pretty clear that SIRT3 (absent in the knockout mice) was necessary, at least as far as AHL is concerned. It's still possible that SIRT3 isn't necessary for anti-aging effects of CR in tissue types that weren't tested (i. e. other than inner ear, brain, and liver tissue), or in mammals other than mice. The case is pretty solid for AHL in mice, but obviously there are many other age-related conditions and other species that should be investigated.
I should apologize for all the biochemical details presented here, but at least they should give you a good indication of just how complicated the effects of CR on aging and longevity can be – and probably are. There's a whole lot of work yet to be done before a reliable anti-aging pill can be developed for humans. Enthusiastic claims that this research "could lead to" therapies to slow down aging in general are basically BS. Yeah, these findings will help, but a heck of a lot more will be needed as well.
(As an example of just how badly misleading journalists who write about this stuff can be, consider this report, which begins with the claim: "In a remarkable demonstration of the ability of calorie restriction to blunt the effects of aging, scientists at the University of Wisconsin-Madison have succeeded in delaying age-related hearing loss in mice." Although the research showed that calorie restriction can do this, it did not produce any new way to do it. Instead, it shows how CR probably works by showing how CR doesn't work if SIRT3 is absent.)
So what's the bottom line here? It's pretty clear from this and many other studies that oxidative damage in cells is a cause of cell death and therefore of various health problems associated with aging. Undoubtedly there are a number of other factors that contribute to aging-related problems, such as cell death due to other causes and weakening or disregulation of the immune system. And even in the case of oxidative damage, there are many ways it can come about, and also many ways it might be inhibited. If you think of aging as a complex disease, like cancer – a point of view that has its detractors – then there are bound to be many causes and contributing factors. And also many ways to inhibit or arrest the process. The example considered here is just one of many.
 | Someya, S., Yu, W., Hallows, W., Xu, J., Vann, J., Leeuwenburgh, C., Tanokura, M., Denu, J., & Prolla, T. (2010). Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction Cell, 143 (5), 802-812 DOI: 10.1016/j.cell.2010.10.002 |
Further reading:
Scientists ferret out a key pathway for aging (11/18/10)
Calorie restriction delays age-related hearing loss, UW study finds (11/18/10)
Scientists ID key protein that links dietary restriction with healthy hearing, aging (12/16/10)
Calorie Restrictions Slow Aging by Enzyme Pathway (11/19/10)
Telomerase can reverse the aging process... sort of
Biologists are, at long last, beginning to understand the molecular processes responsible for aging in complex (multicellular) organisms – and to investigate ways to counteract these processes. We discussed one line of research in this recent article about a particular sirtuin (SIRT3) that helps relieve oxidative stress that can lead to DNA damage, which generally leads, in turn, to cell senescence or death.
While oxidative stress is certainly a significant factor in aging, possibly the most significant, there are others. One of these is the limitation on a cell's ability to undergo cell division in order to produce new cells of the same type. This is especially important in tissues that regularly need to regenerate, such as skin and intestinal tissue. Everyone now knows about telomeres, whose main function is to constitute protective end caps on chromosomes. The limitation on number of cell divisions happens since about 100 base pairs are lost from telomeres during each cell division. When telomeres eventually become too short signals that are similar to those associated with other kinds of DNA damage shut down a cell's ability to divide further. This mechanism indirectly helps mitigate the risks of DNA damage that are present every time a cell divides – an inherently tricky process.
However, this limitation on cell division isn't acceptable during embryonic development, when an organism's cell count is doubling most rapidly. So evolution has provided an enzyme – telomerase – that can rebuild telomeres, but is most active only during embryonic development. Except, of course, in cells that have become cancerous, where the ability to divide without limit is the name of the game. We discussed telomeres and telomerase in some detail a little over a year ago in this article, so you can go there for more.
Because of the risk of cancer, it seems imprudent to reactivate telomerase for the long term within an organism, especially in long-lived animals such as humans. (In animals like mice, which live fast and die young, it's a different matter. Telomerase may remain somewhat active in mice during adulthood. (Mentioned here.)) But what if it were possible to reactivate telomerase for a relatively short period of time (compared to the whole lifespan)... might that provide an opportunity to rebuild telomeres to some extent? Even better, might that reverse, at least to some extent, the ravages of aging?
We now have some research that seems to provide a fairly unambiguous affirmative answer... in a rather special case: Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.
But didn't we just say that mice may retain telomerase activity throughout their lives? Yes, however it's a relatively simple matter to "knock out" the main telomerase gene in mice (Tert). When that's done the resulting strain of knock-out mice – after several generations – have shortened lifespans and a general phenotype of age-related debilities, as one would expect. (The first few generations apparently still have sufficiently long teleomeres.)
Unfortunately, that's not a good enough model, since without a Tert gene, the organism has no way to manufacture telomerase. Simply giving the knock-out mice repeated infusions of telomerase is not a good way to ensure uniform distribution of the enzyme to all of the organism's cells. What to do? The experimenters came up with a rather clever solution. Normally the way that telomerase is activated in cells is by means of an "estrogen receptor" (ER), to which a form of the hormone estrogen (17β-estradiol to be precise) can bind and enable transcription of Tert. This ER can be tweaked so that estrogen binds to it only in the presence of another chemical, 4-hydroxytamoxifen (4-OHT).
A special form of the Tert gene that includes this special ER can be "knocked-in" to the mouse germline. It then turns out that 4-OHT can be efficaciously supplied to a TERT-ER mouse (in the form of a time-release subcutaneous pellet) to turn telomerase expression on and off at the experimenter's will. With that technology in place, the researchers were then able to perform a series of experiments demonstrating, in these special mice, that a month-long burst of telomerase could actually reverse a number of the ill effects of telomerase deprivation.
The first step was to show that without 4-OHT the TERT-ER mice (after a few generations) had many of the same problems, in the same degree, as later generations of knock-out mice that lacked Tert entirely. The TERT-ER mice (all of which were male) showed no signs of telomerase activity. Tissues in highly proliferative organs such as testes, spleen, and intestines showed notable atrophy. Lifespan of TERT-ER mice was about half that of normal ("wild type") mice.
The first test to investigate the effects of telomerase reactivation by means of 4-OHT was done in vitro. Fibroblast cells from TERT-ER mice were cultured and found to be essentially senescent and not undergoing cell cycles. But when the cells were placed in media containing 4-OHT, teleomerase was reactivated, telomeres lengthened, and cell proliferation resumed.
Some TERT-ER mice were then given a 4-week treatment of 4-OHT (subcutaneous pellets). At the end of that treatment there was a marked reversal of the degeneration that has occurred in testes, spleen, liver, and intestinal tissues, as well as resumption of sperm production. Survival time of these treated mice also increased. At the same time, 4-OHT had no effects on control mice that weren't lacking in telomerase and didn't have tissue degeneration.
Noteworthy results were obtained from tests to assess nervous system condition. Proliferation of neural progenitor cells was found to resume in TERT-ER mice treated with 4-OHT. Normal numbers of mature oligodendrocytes reappeared. Lastly, high-level neurological functions were restored, as indicated by resumption of nearly normal olfactory sensitivity.
An interesting conclusion that can be drawn from the neurological results is that neural progenitor cells probably survive loss of telomeres, so that they can rebuild neural cell populations if telomeres are repaired.
The really interesting question, of course, is the extent to which these results may apply, in some form, to humans. Unfortunately, there are a number of reasons to be skeptical. For one thing, telomere shortening is only one factor, and quite possibly not the main one, in human aging. Aging can be thought of as a complex disease, like cancer, with many contributing factors. The consequences of telomere truncation are only one factor.
Further, murine biology has signficant differences from human biology. Mice are less complex organisms, with rather short lifespans. Mice seem to retain some degree of telomerase activity throughout their lives, so they are not as well adapted to going for long periods without it.
It is noteworthy that evidence was not found that TERT-ER mice treated with 4-OHT became more susceptible to cancer. Still, mice don't live very long, and they are adapted to maintain active telomerase. Humans are different. If telomerase is artificially kept active for years in humans, incipient tumorigenicity could be accelerated.
Lastly, it's not necessarily easy to raise human telomerase activity levels in the first place. Although some telomerase-activating factors are known, they have not been tested extensively in humans for long periods of time, so their safety and efficacy profile is not known.
These research results are quite interesting – but they only indicate the need for much more investigation.
Further reading: (* = especially recommended)
* Telomerase reverses ageing process (11/28/10)
* The Curious Case of the Backwardly Aging Mouse (11/29/10)
* Partial reversal of aging achieved in mice (11/29/10)
Harvard scientists reverse the ageing process in mice – now for humans (11/28/10)
Gene reactivation reverses aging-related brain deficits in mice (11/30/10)
Age-Reversing Drugs on the Horizon? Not So Fast (11/29/10)
Telomere Tweaks Reverse Aging in Mice (11/29/10)
Alzheimers and aging advances uncovered (11/29/10)
An enzyme leads the dance of immortality and death (11/29/10)
Scientists Find Way to Partially Reverse Aging in Mice (11/29/10)
While oxidative stress is certainly a significant factor in aging, possibly the most significant, there are others. One of these is the limitation on a cell's ability to undergo cell division in order to produce new cells of the same type. This is especially important in tissues that regularly need to regenerate, such as skin and intestinal tissue. Everyone now knows about telomeres, whose main function is to constitute protective end caps on chromosomes. The limitation on number of cell divisions happens since about 100 base pairs are lost from telomeres during each cell division. When telomeres eventually become too short signals that are similar to those associated with other kinds of DNA damage shut down a cell's ability to divide further. This mechanism indirectly helps mitigate the risks of DNA damage that are present every time a cell divides – an inherently tricky process.
However, this limitation on cell division isn't acceptable during embryonic development, when an organism's cell count is doubling most rapidly. So evolution has provided an enzyme – telomerase – that can rebuild telomeres, but is most active only during embryonic development. Except, of course, in cells that have become cancerous, where the ability to divide without limit is the name of the game. We discussed telomeres and telomerase in some detail a little over a year ago in this article, so you can go there for more.
Because of the risk of cancer, it seems imprudent to reactivate telomerase for the long term within an organism, especially in long-lived animals such as humans. (In animals like mice, which live fast and die young, it's a different matter. Telomerase may remain somewhat active in mice during adulthood. (Mentioned here.)) But what if it were possible to reactivate telomerase for a relatively short period of time (compared to the whole lifespan)... might that provide an opportunity to rebuild telomeres to some extent? Even better, might that reverse, at least to some extent, the ravages of aging?
We now have some research that seems to provide a fairly unambiguous affirmative answer... in a rather special case: Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.
But didn't we just say that mice may retain telomerase activity throughout their lives? Yes, however it's a relatively simple matter to "knock out" the main telomerase gene in mice (Tert). When that's done the resulting strain of knock-out mice – after several generations – have shortened lifespans and a general phenotype of age-related debilities, as one would expect. (The first few generations apparently still have sufficiently long teleomeres.)
Unfortunately, that's not a good enough model, since without a Tert gene, the organism has no way to manufacture telomerase. Simply giving the knock-out mice repeated infusions of telomerase is not a good way to ensure uniform distribution of the enzyme to all of the organism's cells. What to do? The experimenters came up with a rather clever solution. Normally the way that telomerase is activated in cells is by means of an "estrogen receptor" (ER), to which a form of the hormone estrogen (17β-estradiol to be precise) can bind and enable transcription of Tert. This ER can be tweaked so that estrogen binds to it only in the presence of another chemical, 4-hydroxytamoxifen (4-OHT).
A special form of the Tert gene that includes this special ER can be "knocked-in" to the mouse germline. It then turns out that 4-OHT can be efficaciously supplied to a TERT-ER mouse (in the form of a time-release subcutaneous pellet) to turn telomerase expression on and off at the experimenter's will. With that technology in place, the researchers were then able to perform a series of experiments demonstrating, in these special mice, that a month-long burst of telomerase could actually reverse a number of the ill effects of telomerase deprivation.
The first step was to show that without 4-OHT the TERT-ER mice (after a few generations) had many of the same problems, in the same degree, as later generations of knock-out mice that lacked Tert entirely. The TERT-ER mice (all of which were male) showed no signs of telomerase activity. Tissues in highly proliferative organs such as testes, spleen, and intestines showed notable atrophy. Lifespan of TERT-ER mice was about half that of normal ("wild type") mice.
The first test to investigate the effects of telomerase reactivation by means of 4-OHT was done in vitro. Fibroblast cells from TERT-ER mice were cultured and found to be essentially senescent and not undergoing cell cycles. But when the cells were placed in media containing 4-OHT, teleomerase was reactivated, telomeres lengthened, and cell proliferation resumed.
Some TERT-ER mice were then given a 4-week treatment of 4-OHT (subcutaneous pellets). At the end of that treatment there was a marked reversal of the degeneration that has occurred in testes, spleen, liver, and intestinal tissues, as well as resumption of sperm production. Survival time of these treated mice also increased. At the same time, 4-OHT had no effects on control mice that weren't lacking in telomerase and didn't have tissue degeneration.
Noteworthy results were obtained from tests to assess nervous system condition. Proliferation of neural progenitor cells was found to resume in TERT-ER mice treated with 4-OHT. Normal numbers of mature oligodendrocytes reappeared. Lastly, high-level neurological functions were restored, as indicated by resumption of nearly normal olfactory sensitivity.
An interesting conclusion that can be drawn from the neurological results is that neural progenitor cells probably survive loss of telomeres, so that they can rebuild neural cell populations if telomeres are repaired.
The really interesting question, of course, is the extent to which these results may apply, in some form, to humans. Unfortunately, there are a number of reasons to be skeptical. For one thing, telomere shortening is only one factor, and quite possibly not the main one, in human aging. Aging can be thought of as a complex disease, like cancer, with many contributing factors. The consequences of telomere truncation are only one factor.
Further, murine biology has signficant differences from human biology. Mice are less complex organisms, with rather short lifespans. Mice seem to retain some degree of telomerase activity throughout their lives, so they are not as well adapted to going for long periods without it.
It is noteworthy that evidence was not found that TERT-ER mice treated with 4-OHT became more susceptible to cancer. Still, mice don't live very long, and they are adapted to maintain active telomerase. Humans are different. If telomerase is artificially kept active for years in humans, incipient tumorigenicity could be accelerated.
Lastly, it's not necessarily easy to raise human telomerase activity levels in the first place. Although some telomerase-activating factors are known, they have not been tested extensively in humans for long periods of time, so their safety and efficacy profile is not known.
These research results are quite interesting – but they only indicate the need for much more investigation.
Further reading: (* = especially recommended)
* Telomerase reverses ageing process (11/28/10)
* The Curious Case of the Backwardly Aging Mouse (11/29/10)
* Partial reversal of aging achieved in mice (11/29/10)
Harvard scientists reverse the ageing process in mice – now for humans (11/28/10)
Gene reactivation reverses aging-related brain deficits in mice (11/30/10)
Age-Reversing Drugs on the Horizon? Not So Fast (11/29/10)
Telomere Tweaks Reverse Aging in Mice (11/29/10)
Alzheimers and aging advances uncovered (11/29/10)
An enzyme leads the dance of immortality and death (11/29/10)
Scientists Find Way to Partially Reverse Aging in Mice (11/29/10)
Flocculent spiral NGC 2841
Flocculent spiral NGC 2841
NGC 2841 – click for 1000×800 image
Star formation is one of the most important processes in shaping the Universe; it plays a pivotal role in the evolution of galaxies and it is also in the earliest stages of star formation that planetary systems first appear.
Yet there is still much that astronomers don’t understand, such as how do the properties of stellar nurseries vary according to the composition and density of the gas present, and what triggers star formation in the first place? The driving force behind star formation is particularly unclear for a type of galaxy called a flocculent spiral, such as NGC 2841 shown here, which features short spiral arms rather than prominent and well-defined galactic limbs.
In an attempt to answer some of these questions, an international team of astronomers is using the new Wide Field Camera 3 (WFC3) installed on the NASA/ESA Hubble Space Telescope to study a sample of nearby, but wildly differing, locations where stars are forming. The observational targets include both star clusters and galaxies, and star formation rates range from the baby-booming starburst galaxy Messier 82 to the much more sedate star producer NGC 2841.
NGC 2841 – click for 1000×800 image
Wide Field Imager view of a Milky Way look-alike, NGC 6744
Wide Field Imager view of a Milky Way look-alike, NGC 6744 (6/1/11)
NGC 6744 – click for 1280×1078 image
This picture of the nearby galaxy NGC 6744 was taken with the Wide Field Imager on the MPG/ESO 2.2-metre telescope at La Silla. The large spiral galaxy is similar to the Milky Way, making this image look like a picture postcard of our own galaxy sent from extragalactic space. The picture was created from exposures taken through four different filters that passed blue, yellow-green, red light, and the glow coming from hydrogen gas. These are shown in this picture as blue, green, orange and red, respectively.
NGC 6744 – click for 1280×1078 image
"Rose" of Galaxies
"Rose" of Galaxies (4/20/11)
Arp 273 – click for 987×1000 image
The newly released Hubble image shows a large spiral galaxy, known as UGC 1810, with a disk that is distorted into a rose-like shape by the gravitational tidal pull of the companion galaxy below it, known as UGC 1813. A swath of blue jewel-like points across the top is the combined light from clusters of intensely bright and hot young blue stars. These massive stars glow fiercely in ultraviolet light.
The smaller, nearly edge-on companion shows distinct signs of intense star formation at its nucleus, perhaps triggered by the encounter with the companion galaxy.
Arp 273 – click for 987×1000 image
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