Tengion is one of the research groups attempting to tissue engineer replacement sections of intestine: "Tengion has demonstrated that smooth muscle cells seeded on its biological scaffolding and then implanted in rodents exhibit functional regeneration of both the inner lining of epithelial cells and the surrounding layers of small intestine smooth muscle cells in as little as eight weeks post-implantation. ... The regeneration of small intestine from smooth muscle cells using our technology platform represents an important step forward in the development of functional, regenerated organs. Our goal is to translate preclinical data and proof of concept findings into clinical programs that could represent a broad range of medical treatment possibilities for patients in need of new bladders, kidneys and other organs. ... In this preclinical study, patch and tubular constructs were implanted in rodent small intestines and histologically evaluated for evidence of regeneration of the neo-mucosa and muscle layers. In as little as eight weeks post-implantation, laminarly organized neo-mucosa and muscle layer bundles were demonstrated, supporting the approach of using autologous smooth muscle cells and biomaterial combination products to spur regeneration of the small intestine. Patients with short bowel syndrome have typically undergone extensive small intestine resectioning and may become dependent on parenteral nutrition, a costly treatment associated with multiple complications, and could potentially benefit from a regenerative medicine approach."

Link: http://www.marketwatch.com/story/tengion-organ-regeneration-platform-technology-demonstrates-ability-to-regenerate-small-intestine-in-preclinical-models-data-published-in-regenerative-medicine-2011-11-07

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A good demonstration of the state of the art of tissue engineering: "Last spring, a research team at Japan's RIKEN Center for Developmental Biology created retina-like structures from cultured mouse embryonic stem cells. This week, the same group reports that it's achieved an even more complicated feat - synthesizing a stem-cell-derived pituitary gland. The pituitary gland is a small organ at the base of the brain that produces many important hormones and is a key part of the body's endocrine system. It's especially crucial during early development, so the ability to simulate its formation in the lab could help researchers better understand how these developmental processes work. ... The experiment wouldn't have been possible without a three-dimensional cell culture. The pituitary gland is an independent organ, but it can't develop without chemical signals from the hypothalamus, the brain region that sits just above it. With a three-dimensional culture, the researchers could grow both types of tissue together, allowing the stem cells to self-assemble into a mouse pituitary. ... Using this method, we could mimic the early mouse development more smoothly, since the embryo develops in 3-D in vivo. ... Fluorescence staining showed that the cultured pituitary tissue expressed the appropriate biomarkers and secreted the right hormones. The researchers went a step further and tested the functionality of their synthesized organs by transplanting them into mice with pituitary deficits. The transplants were a success, restoring levels of glucocorticoid hormones in the blood and reversing behavioral symptoms, such as lethargy."

Link: http://www.technologyreview.com/biomedicine/39108/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Naked mole rats are of interest to researchers because they can live nine times as long as comparable rodent species: this implies that they are a good place to look for determinants of longevity and important mechanisms of aging. You can go far in biology by comparing similar species that nonetheless exhibit sharply defined differences in your area of interest. The naked mole rat genome was sequenced and published this year, but research into the genetics of aging in the species that predates the availability of the full genome is still arriving at the presses. For example, there is this open access paper:

RNA Sequencing Reveals Differential Expression of Mitochondrial and Oxidation Reduction Genes in the Long-Lived Naked Mole-Rat When Compared to Mice

The naked mole-rat is not only the longest-lived rodent, but has a much longer lifespan than expected for its relatively small body size and has been shown to be extremely resistant to neoplasia. Furthermore, since a number of other rodents including mice, rats and guinea pigs already have had their genome sequenced, the naked mole-rat is a prime candidate for comparative genomics studies. ... Using a combination of 2nd-generation sequencing platforms, [we] were able to compare gene expression between wild-derived mice and naked mole-rats without using a naked mole-rat reference genome.

Gene expression is the process by which proteins are produced from the DNA blueprint. How much of any given protein is produced at any given time, and how that changes over time and in response to circumstances, is at least as important as what the protein is. Examining different levels of protein production between neighboring species is a good way to narrow down the biological mechanisms that explain their differences. In this case:

Within over-expressed genes in the naked mole-rat, genes associated with oxidoreduction were strongly overrepresented as well as genes associated with mitochondria and more specifically mitochondrial matrix. Consistent with the free radical theory of ageing, the over-expression of genes related to oxidoreduction could protect the naked mole-rat from reactive oxygen species. [With caveats, and] in view of the hypothesis that mitochondria play a major role in mammalian ageing, these results point towards a putative role for oxidoreduction and mitochondrial alterations in the long lifespan of the naked mole-rat.

You might compare this view with the membrane pacemaker hypothesis, that has naked mole rat longevity stemming from the fact that vulnerable cell components such as mitochondria are have a composition that renders them resistant to damage caused by free radicals, the reactive byproducts of cellular-fuel-generation taking place within mitochondria. The mitochondria themselves are the first target for those free radicals, and if you look back in the Fight Aging! archives, you'll find an explanation as to how damage to mitochondria can spiral into damage throughout the body - and hence aging.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A good example of the next generation of targeted cancer therapies is outlined at the Technology Review: "scientists at the National Cancer Institute have developed a possible solution that involves pairing cancer-specific antibodies with a heat-sensitive fluorescent dye. The dye is nontoxic on its own, but when it comes into contact with near-infrared light, it heats up and essentially burns a small hole in the cell membrane it has attached to, killing the cell. To target the tumor cells, the researchers used antibodies that bind to proteins that are overexpressed in cancer cells. ... Normal cells may have a hundred copies of these antibodies, but cancer cells have millions of copies. That's a big difference. ... The result is that only cancer cells are vulnerable to the light-activated cascade. ... The researchers tested the new treatment in mice and found that it reduced tumor growth and prolonged survival. There are a few kinks to work out before the system can be adapted for humans, though. For instance, the researchers couldn't test the treatment's effect on large tumors, since killing off too many cells at once caused cardiovascular problems in the mice. Finding the right cancer-cell markers to pair with the dye may also prove difficult. For example, HER-2, one of the proteins targeted in the study, is only expressed in 40 percent of breast-cancer cells in humans. Still, the lack of toxicity associated with the treatment is a huge advantage,"

Link: http://www.technologyreview.com/biomedicine/39082/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The best communities involved in advocacy and outreach are balanced somewhere between eagerness ("It's all so obvious, look what we could achieve!") and frustration ("But it's all so obvious - why don't they get it?"). Advocacy is hard despite its simplicity and time-worn, well-understood nature: it is hard because it is slow and incremental toil at the best of times, the human relations equivalent of banging two rocks together to make fire. You talk to people, you persuade people to your way of looking at things over and over and over again, making tiny little gains each time. For longevity science, the people willing to do this work are generally the bright sparks, the early adopters and foresightful folk who see the opportunity to defeat aging, see how plausible it is, and are full of enthusiasm for this goal. They are then run into the meatgrinder of tiny, incremental progress in persuading the world one person at a time.

Occasionally this isn't pretty, and hence the frustration. None of us are getting any younger, and while the science is so very obviously heading the right direction to produce working rejuvenation biotechnology, it is doing so very, very slowly. Only a minuscule fraction of the scientific community are working on relevant projects, there is next to no funding, and only a minuscule fraction of the public at large care one way or another. That needs to change, and changing it is slow going.

Here's some frustration from the Russian side of the community, translated, and further smoothed out by my edits:

It's aging that kills people. Also it's stupidity and greed that kill people. It exactly the stupidity and greed that prevents people from doing much to survive. The society spends an abysmally small amount of effort on life extension. Minimal interest and microscopic funding goes to studying of fundamental mechanisms of aging. Resources are being spent on any any old thing, but not on longevity. Years go by, and people become dung and rot in their graves. Because of their own stupidity and imbecility of others.

Almost everyone who comes to somebody's funeral should keep saying: "We are the sick people, we killed you by our passivity. Moreover, we keep on bringing death further on. The thought to identify the underlying reasons of death and to try to eliminate them doesn't even sneak into our empty minds. It's actually only money and pleasure that matter to us, and in indulging that we seek our own death."

I would have written "ignorance" in place of "stupidity," but Russian has a somewhat different set of overlapping meanings for words involving lack of knowledge, poor application of knowledge, and lack of intelligence. "Foolishness" or "unreasonableness" is as good a translation as "stupidity" from the original, I think. To my eyes people are rarely forthrightly stupid, but the small slice of attention that a person gives to matters outside his focus looks stupid from a distance - and most people give next to no attention to longevity science. That is foolish in this day and age, as it amounts to remaining blind to a tremendous opportunity just because you didn't take a small amount of time and effort to check on it.

There is a brass ring to be grasped: as someone who has spent a fair amount of time following the science and biotechnology, I can say with some conviction that it is clearly possible for us to engineer our way to agelessness in stages within a few decades from where we stand today. To do that, however, will require radical success in advocacy, fundraising, and growing the longevity science community over the next ten years.

Thus frustration stems from the size of the opportunity, the sheer obviousness of the imperative to defeat aging once you grasp it, and the feeling that the opportunity to achieve this goal in our lifetimes might be slipping from our grasp despite our progress to date. That's what things look like in the early stages of an exponential growth curve; it seems as though you'll never get there in time, but it takes off late in the game. Unfortunately it's also what things look like in the early stages of linear growth that will remain small - see the cryonics community, for example. We can't tell how the future will turn out, but we have to keep coming back to work at building it: the way to ensure the next few decades go badly for longevity science is to fail to try to do better.

You can't blame the rest of the world for not listening if you're not talking to them in the right way.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A group of researchers found that eating 45 grams of dark chocolate in a day for a period of 16 weeks can potentially reduce the cholesterols levels of diabetic patients.

Understanding Bad Cholesterol

There are two types of cholesterols in the body: the good and bad. Low Density Lipoprotein (LDL) is referred to as bad cholesterol since high levels of LDL results to a higher risk of developing coronary and cardiovascular diseases. It interferes with healthy blood flow by sticking on artery walls and forming a thick and hard cholesterol plaque. This narrows the blood passages in a process called atherosclerosis.

There’s a good type of cholesterol, on the other hand, that is essential in preventing and reversing the adverse effects of LDL accumulation by extracting the bad cholesterol from the walls of the artery and removing them from the body through the liver. The body needs to have more of the good cholesterol in order to function properly. Good cholesterol is responsible for promoting the fluidity and permeability of membranes and it is also essential in the manufacturing of bile acids that breaks down fats and fat-soluble vitamins like vitamin K, vitamin E, vitamin D and vitamin A.

A person’s bad cholesterol level is greatly influenced by his diet and hereditary condition. Eating foods with high contents of saturated fats will result to the accumulation of bad cholesterol in the blood. Rich sources of saturated fats are dairy products and meat. Vegetable oils from cocoa, palm and coconut are also rich in saturated fats. There is a specific health condition which may result to high LDL levels despite minimal intake of saturated fats. This is called familial hypercholesterolemia which literally means more cholesterol in the blood. It can be inherited and is usually brought about by the lack of cholesterol receptors in the cells of the liver. Note that the liver is responsible for the processing of LDL cholesterols. This condition can result to atherosclerosis and other coronary diseases in early adulthood. High cholesterol levels have also been linked by different studies to diabetes.

There will always be a natural way of reducing the risk of health conditions such as coronary diseases and diabetes. Medical experts will always recommend healthy diet and active lifestyle on top of anything else. A group of researchers from the Hull York Medical School of the University of Hull found that eating one of our most favorite bitter-sweet treats can reduce the cholesterol levels of diabetic patients.

Dark Chocolate against High Cholesterol in Diabetics

An Overview

A group of researchers from the Hull York Medical School published a study in Diabetic Medicine saying that dark chocolate has the capacity to lower cholesterol levels in people suffering from diabetes. Their findings may sound incongruous but they have found that eating 45 grams of dark chocolate reduced the cholesterol levels of 12 diabetic participants in a study period of 4 months. The head of the research team and professor of diabetes and endocrinology, Steve Atkins, said that their study demonstrated that dark chocolate can result to the reduction of cardiovascular risk caused by insulin resistance and being overweight. The 12 participants had type 2 diabetes, a condition wherein cells are weakly responsive to insulin naturally produced by the body.

The Benefits of Polyphenols

The researchers linked the positive results of their study to polyphenols found in cocoa. This compound has a powerful anti-inflammatory property, making it a strong and effective antioxidant. As its natural function, polyphenols protect the cells from damage caused by free radicals and prevent the oxidation of LDL cholesterol which causes it to become glued to artery walls, causing atherosclerosis. A person can maintain high levels of polyphenols in the body by eating foods rich in polyphenols; topping the list is cacao alongside green tea and wine. The researchers suggested for chocolate manufacturers to create smaller packages of dark chocolate bars in order to give individuals with diabetes a better way to manage their intake of polyphenol-rich chocolates and so they can better take advantage of its benefits in lowering their blood cholesterol levels.

The Methodology and Results

The researchers recruited a group of 12 diabetic patients and gave them 3 bars of 15-gram dark chocolate bars per day for a period of 16 weeks. The chocolate bars contained 85 percent cocoa and other placebo bars did not have any cocoa content and was only dyed to achieve the same color as dark chocolate. They said that the bars were no bigger than a banana and, unlike the usual way of eating a banana, the bars were eaten at different points of the day. The researchers also said that dark chocolate has a low glycaemic index which related to the release of glucose into the blood stream from sugars.

Though the researchers used a very small group, the participants did not report any increase in weight nor did they experience problems in controlling their blood sugar levels brought by their existing health condition. They said that the study is only a preliminary of more and bigger studies to come and they will be releasing more information regarding their findings in the following days.

Foods against Bad Cholesterol

The body’s bad cholesterol level is a major health concern. High levels of bad cholesterol in the body may result to coronary problems and other serious health problems. But eating the right kind of foods and maintaining a healthy lifestyle can help in managing cholesterol levels and promoting a healthier body.

• The body needs soluble fiber in order to sweep out saturated fats which can increase the levels of bad cholesterol in the blood. Soluble fiber can be found in oatmeal, prunes, barley, pears apples and kidney beans. Including some of the fiber-rich foods in ones daily diet can reduce the risk of developing diseases caused by bad cholesterol.

• Foods rich in omega-3 fatty acids like salmon, tuna, sardines, herring, lake trout and mackerel can also help in lowering bad cholesterol levels. Omega-3 fatty acids help in reducing blood pressure by preventing the clotting of the blood and the accumulation of bad cholesterol on the walls of the arteries.

• Almonds, walnuts and other kinds of nuts are rich in polyunsaturated fatty acids which helps maintain the smooth passage of blood through the blood vessels and reduce blood cholesterol levels. Eating around 43 grams of nuts can lower the risk of developing heart diseases according to the Food and Drug Administration. But keep in mind that nuts are packed with calories so eating a handful can be enough.

• Other foods that can lower bad cholesterol levels are those fortified with plant sterols like yogurt drinks, orange juice and margarine. Eating at least 2 grams of plant sterols through rich food sources can lower LDL cholesterol by more than 10 percent.

Sources:
nutraingredients.com
medicinenet.com
raysahelian.com
mayoclinic.com
webmd.com

Discuss this post in Frank Mangano’s forum!

The Science for Life Extension Foundation is a Russian organization consisting of advocates and aging researchers. They are similar to the SENS Foundation in that they undertake a mix of fundraising, directing research, organizing events, advocacy for longevity science, and publishing on potential methodologies to extend the healthy human life span. These two groups even share some members and advisors in common - it's a small world these days, after all, and aging research is not a large community to begin with. That is one of many things we like to see change over the next decade or two: if you want rapid progress, there need to be many researchers at work.

The Science for Life Extension Foundation has published a number of professional quality documents that can be downloaded in PDF format from their website. Unfortunately not all of them are available in English, and automated translation of PDFs remains somewhat hit and miss. I did want to direct your attention to one of the documents, however, which is entitled "25 Scientific Ideas of Life Extension." It is a very elegantly designed, very clear booklet aimed at investors. The PDF packages up a series of scientific research programs aimed at extending human life into compelling elevator pitches - but just saying that doesn't do it justice. It really is very well done indeed, and you should take a look:

I picked out one of the twenty-five that focuses on a research theme you might be familiar with, as I've mentioned it in the past. If you look back in the Fight Aging! archives, you can read more about Cuervo's work on autophagy and lysosomal receptors:

• A Little More On Preventing Decline in Liver Function With Age
• An Update on Cuervo's Autophagy Research

In experiments, livers in genetically modified mice 22 to 26 months old, the equivalent of octogenarians in human years, cleaned blood as efficiently as those in animals a quarter their age. By contrast, the livers of normal mice in a control group began to fail. ... While her paper does not show increased survival rates among the mice, le Couteur, who has advised her recently on the research, says Cuervo does have data on improved survival rates which she intends to publish.

The Vegas Group is a yet-to-be-built community initiative intended to bring longevity science to the open biotechnology and DIYbio communities - and from there reverse engineer and make ready for human use the most promising longevity-enhancing technologies demonstrated in mice in the laboratory. We are entering an age of medical tourism, and the clinics and laboratories of Asia will be happy to accept business and open source biotechnologies generated by DIYbio work in the US. At this stage, I'm still thinking through the project: breaking it down into manageable chunks, and considering what I should work on first:

The path to this future involves networking and community building in a whole new and different direction from that taken by much of the longevity advocacy community - and the construction of a codex of information, a how-to manual of recipes for replicating specific products of the formal research community in longevity science. ... any step one for me will involve considering the codex: what it is, and how it will be constructed, maintained, and made useful to the seeds of what will be the Vegas Group - however that organization ultimately comes about, and whatever form it ultimately takes.

As the cost of biotechnology falls, so is the door opened to much wider development and innovation, wherein lab cooperatives host a mix of hobbyists, moonlighting professionals, and semi-professionals who collaborate on a range of their own projects. Ultimately, low-cost desktop biotech toolkits will be developed and a community of tens or hundreds of thousands of developers will contribute from their homes - just as is the case for open source software development today. With computers in mind, a good historical analogy for the present state of the small DIYbio community is in fact the Homebrew Computer Club in the mid 1970s, prior to the introduction of the first popular personal computer kit. Some small but enthusiastic individuals and groups are designing, building, and selling biotech hardware - such as PCR machines - that will ultimately be the components of a home laboratory, but matters are not yet at that stage of take-off that will see dozens of companies founded and many more people join the community in a short period of years. That lies ahead. The wave is coming, in its own time, and I would like to be positioned to take advantage of it.

All journeys start with the first steps, and I'm in favor of incremental approaches to development. Make something small, a minimum viable product that is the most elementary building block that can stand on its own and still contribute to the ultimate goal. Release it, obtain feedback, and then start on the next building block - and repeat that process until you have as fully as possible realized your initial vision. There will be much to learn along the way, and small building blocks coupled with "release early, release often" make that learning less painful.

Given a large idea, the challenge is often finding that starting point. From the broad high level outline of the Vegas Group, I focused on the codex: the necessary how-to documents and body of knowledge that will enable people to participate. As a general rule, technical communities are terrible at documentation - and that lack of documentation is a real hurdle to recruitment and growth. It could be argued that the DIYbio community isn't yet at the point where it could benefit greatly from a codex: there are other tasks to be completed first relating to hardware. But time is ticking, and progress is being made. The period of being too early won't last forever, and establishing even the skeleton of a practical longevity science codex at hobbyist or non-profit speed will be a process that takes years.

The codex itself is a very large project: something large enough to found a company on in and of itself. There are any number of questions: how best to discover the business models that work to efficiently produce accurate reverse engineering from published papers on longevity-related biotechnology; how best to structure the information presented; how to organize writers and researchers; how to even assemble and prioritize the list of materials needed; and so on ad infinitum.

Thus a fairly narrow initial project for the codex must be identified, so that the first group of volunteers to work on it can run into all the brick walls and fall into all of the potholes without risking a great deal if it all fails. Small projects are easy to scrap, rework, and start over if necessary - and that is a tremendous advantage when you don't yet know the detailed recipe for success. Along the way the volunteers will come to an understanding of how best to make assembly of the broader codex work as a process.

What is this first codex project, though? I propose that reverse engineering and documentation of mitochondrial protofection is a good candidate. This is a technique by which mitochondrial DNA is replaced throughout an individual's cells, and was first demonstrated in mice back in 2005. As you might know, progressively accumulated damage to mitochondrial DNA is one of the causes of aging, as described by the mitochondrial free radical theory of aging. Future rejuvenation biotechnology must include a way to either permanently work around this form of damage, such as through the methodology advocated by the SENS Foundation, or periodically repair it - say once every two to three decades.

Why protofection? In a nutshell:

• It is comparatively easy to explain to a non-technical audience.
• It fits with the SENS vision for rejuvenation biotechnology.
• It has already been demonstrated to work, so at least one group of researchers knows exactly how to do it.
• It is old enough that this and related knowledge may have spread somewhat, making it more amenable to reverse engineering.

Protofection works in mice, but since that demonstration six years ago next to nothing has been heard of it - just a few publications indicative of a slow exploration in search of possible FDA-approved applications. The FDA does not consider aging a disease, however, and therefore its regulators will not approve any treatment that aims to intervene in aging or achieve rejuvenation. That unfortunate fact is well known, and thus there is little funding available for attempts to treat aging: potential technologies are instead subverted into the development of limited treatments for late stage age-related diseases. The silence regarding protofection is probably another good example of the way in which the present regulatory apparatus holds back progress, as developing protofection for safe general human use is an obvious course of action based on the weight of evidence linking mitochondrial DNA damage and aging. Yet it isn't happening.

Given that a number of years have passed since the viability of protofection was demonstrated, it should be an easier target for reverse engineering and documentation of processes than more recent developments. By which I mean that it should be easier to find researchers and post-graduates unconnected with the work who nonetheless know enough to write on the topic.

Protofection is also (I hope) narrow enough not to generate a true mountain of supporting needs in terms of how-to documents. Part of the process of discovery is to understand how to develop the initial list of documents required for the codex, starting from a high-level goal like "let's reverse engineer protofection, make reproducing it comprehensible to the semi-professional DIYbio volunteer, and release that documentation under a Creative Commons license" and working all way down to the brass tacks and petri dishes. Protofection, while something that can be explained in a few short sentences, stands at the top of a sizable pyramid of techniques and knowledge in biotechnology: how to work with DNA, how to manage your own laboratory equipment, how to keep cell cultures, and so on for a long list of topics.

If this takes a few years to get right, that's fine by me. It will provide a blueprint for doing the same to other areas of biotechnology, and by that time there should be more people interest in helping out - both for longevity science and for their own areas of interest.

A long post from MSNBC's Cosmic Log: "The quest for immortality goes back to Adam and Eve, but now some smart people are getting serious about actually bringing it within their grasp. And they're getting more attention as well. Let's take Aubrey de Grey, for example: The British gerontologist has been beating the drum for anti-aging therapies for years. He plays a prominent role in a recently published book on the immortality quest titled 'Long for this World,' a new documentary called 'To Age or Not to Age' and a just-published commentary on the science of aging. In this week's issue of Science Translational Medicine, de Grey and nine other co-authors urge the United States and other nations to set up a Project Apollo-scale initiative to avert the coming 'global aging crisis.' The experts' prescription includes a campaign to raise the general public's awareness about lifestyle changes that can lead to longer and healthier lives; a lab-based effort to develop anti-aging medicines; and a push for new techniques to repair, restore or replace the cellular and molecular damage done by age. ... There is this misunderstanding that aging is something that just happens to you, like the weather, and cannot be influenced. The big surprise of the last decades is that, in many different animals, we can increase healthy life span in various ways."

View the Article Under Discussion: http://cosmiclog.msnbc.msn.com/_news/2010/07/15/4685717-reaching-for-immortality

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

As the Smithsonian notes, "It won't be long before surgeons routinely install replacement body parts created in the laboratory. ... Anthony Atala works in the body shop of the future. ... he and his colleagues use human cells to grow muscles, blood vessels, skin and even a complete urinary bladder. Much of the work is experimental and hasn't yet been tested in human patients, but Atala has implanted laboratory-grown bladders into more than two dozen children and young adults born with defective bladders that don't empty properly, a condition that can cause kidney damage. The bladders were the first lab-generated human organs implanted in people. If they continue to perform well in clinical tests, the treatment may become standard not only for birth defects of the bladder but also for bladder cancer and other conditions. ... Regenerative medicine's once-wild ideas are fast becoming reality. Late last year, Organovo, a biotech company in San Diego, began distributing the first commercially available body-part printer. Yes, you read correctly: a printer for body parts. Using the same idea as an ink-jet printer, it jets laser-guided droplets of cells and scaffold material onto a movable platform. With each pass of the printer head, the platform sinks, and the deposited material gradually builds up a 3-D piece of tissue. Regenerative medicine laboratories around the world have relied on the printer to generate pieces of skin, muscle and blood vessels. Atala's lab has used the technology to construct a two-chambered mouse-size heart in about 40 minutes."

View the Article Under Discussion: http://www.smithsonianmag.com/specialsections/40th-anniversary/97123514.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

An open access paper: "Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline."

Link: http://dx.doi.org/10.1155/2012/194821

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Possibly an example of overthinking the issue at the JET, but the section on Finot illustrates that our era does not enjoy a monopoly on rational thinking about extending the healthy human life span: "The beginning of the modern period in the pursuit of radical human enhancement and longevity can be traced to fin-de-siecle/early twentieth-century scientific and technological optimism and therapeutic activism. The works of several authors of the period - Fedorov, Stephens, Bogdanov, Nietzsche and Finot - reveal conflicting ideological and social pathways toward the goals of human enhancement and life extension. Each author represents a particular existing social order, and his vision of human advancement may be seen as a continuation and extension of that order. Therefore, the pursuit of life extension may be considered a fundamentally conservative (or conservationist) enterprise. ... First, these adaptations may question the claims of a particular ideology for supremacy in the promotion of life-extension and life-enhancement. The claims that atheism, capitalism or hedonism are more conducive to the pursuit of longevity, can be countered by historical examples where religion, socialism or asceticism were the foundations. No ideological system seems to have a monopoly, however strongly it asserts that it constitutes the rock-solid ground for this pursuit. It may be that, rather than providing such a foundation, political ideologies enlist the hope for life extension to increase their appeal."

View the Article Under Discussion: http://jetpress.org/v21/stambler.htm

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

A lot of work has taken place in recent years on killing cancer cells by heating targeted nanoparticles. Here is an example of the present state of the art: "When irradiated with light, gold nanoparticles become hot quickly, hot enough to generate explosive microbubbles that will kill nearby cancer cells ... To boost this approach, researchers [have] developed a method for creating supramolecular assemblies of gold nanoparticles that function as highly efficient photothermal agents of a size designed to optimize their delivery to tumors. ... They first took gold nanoparticles, 2 nanometers in diameter, and decorated the nanoparticles' surface with adamantane. They then added two other constructs: cyclodextrin attached to a biocompatible polymer known as polyethylenimine, and adamantane linked to polyethylene glycol, another biocompatible polymer. When combined in various ratios, these three constructs quickly assemble into nanoparticles with well defined sizes ranging from 40 to 118 nanometers in diameter. Once the complexes were purified, the researchers then attached a tumor targeting molecule to the surface of the resulting supramolecular complexes. ... when irradiated with a laser beam, the temperature of the assemblies rapidly soared above 374 C, the temperature at which explosive microbubbles form."

View the Article Under Discussion: http://www.physorg.com/news194078270.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Most known cancer suppression genes and mutations shorten life in laboratory mice, as they suppress the mechanisms of cell replication needed to maintain tissues. There are exceptions that have emerged as researchers find more sophisticated methods of genetic engineering to work around these limitations, but this life-extending example of gene engineering seems to be more straightforward than most: "Mice with an extra dose of a known anti-cancer gene lose weight even as their appetites grow. Not only that, but [the] animals also live longer, and that isn't just because they aren't getting cancer, either. ... One of the animals' youthful secrets is hyperactive brown fat, which burns energy instead of storing it. The findings add to evidence that tumor suppressors aren't designed only to protect us against cancer, the researchers say. They also point to new treatment strategies aimed to boost brown fat and fight aging. ... Tumor suppressors are actually genes that have been used by evolution to protect us from all kinds of abnormalities. ... In this case, the researchers studied a tumor suppressor commonly lost in human cancers. Mice with an extra copy of the gene known as Pten didn't get cancer, but that's not the half of it. Those mice were also leaner, even as they ate more than controls ... That suggested that the animals were experiencing some sort of metabolic imbalance - and a beneficial one at that. Cancer protection aside, the animals lived longer than usual. They were also less prone to insulin resistance and had less fat in their livers. Those benefits seem to trace back to the fact that those Pten mice were burning more calories thanks to overactive brown fat."

Link: http://www.sciencedaily.com/releases/2012/03/120306131252.htm

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The near future of organ transplants will become very varied, as a range of different viable types of technology are presently undergoing active development. A short list looks much like this:

• Incremental progress in old-style organ transplants, such as improving the donation system, allowing organs to be stored outside the body for longer periods of time, and so forth.
• Decellularization, in which a donor organ is stripped of cells, leaving only the scaffold of the extracellular matrix. The scaffold is repopulated from the patient's cells, removing the possibility of immune rejection and need for immunosuppressant drugs.
• Electromechanical and bioartificial organs, including hearts, lungs, and kidneys, continue to improve at a good pace. New types of small artificial organ are becoming possible thanks to advances in materials science.
• Creating organ tissue and scaffolds from scratch through a variety of methods, such as the 3-D printing pioneered by a number of groups.
• Xenotransplantation, the use of animal organs for human patients, is also becoming more viable as a near-term prospect.
• Lastly, there are the researchers who aim to rebuild damaged organs in situ through manipulation of stem cells and signaling processes in normal regeneration.

There will be a great deal of innovation and healthy competition over the next two decades before this larger cycle of technological progress in medicine settles down to a few mature and tried and tested ways of fixing broken and age-damaged organs in the body.

To add to the list of strategies, I noticed an article today on a possible middle path between old-style donor transplants (immunosuppressant drugs and all) and the near future of organs that are populated by the patient's own stem cells. It may be possible to use the knowledge acquired by stem cell researchers to date in order to minimize or completely remove the risk of immune rejection of a donor organ:

In a standard kidney transplant, the donor agrees to donate their kidney. In the approach being studied, the individual is asked to donate part of their immune system as well. The process begins about one month before the kidney transplant, when bone marrow stem cells are collected from the blood of the kidney donor using a process called apheresis. The donor cells are then sent to the University of Louisville to be processed, where researchers enrich for "facilitating cells" believed to help transplants succeed. During the same time period, the recipient undergoes pre-transplant "conditioning," which includes radiation and chemotherapy to suppress the bone marrow so the donor's stem cells have more space to grow in the recipient's body.

Once the facilitating cell-enriched stem cell product has been prepared, it is transported back to Northwestern, where the recipient undergoes a kidney transplant. The donor stem cells are then transplanted one day later and prompt stem cells to form in the marrow from which other specialized blood cells, like immune cells, develop. The goal is to create an environment where two bone marrow systems exist and function in one person. Following transplantation, the recipient takes anti-rejection drugs which are decreased over time with the goal to stop a year after the transplant.

...

Less than two years after her successful kidney transplant, 47-year-old mother and actress Lindsay Porter of Chicago, is living a life that most transplant recipients dream of - she is currently free of anti-rejection medications and says at times, she has to remind herself that she had a kidney transplant. ... Doctors are hopeful that Porter will not need immunosuppressive drugs long-term, given her progress thus far.

You might look on this as creating a form of engineered chimerism. We know that some animals and humans exist with, for example, multiple blood types and genetically distinct systems in their body as a result of the fusion of two zygotes in the womb. These individuals don't seem to suffer any great harm from being chimeric, which might be taken as a promising sign for the long-term prospects of this form of stem cell medicine.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Another aspect of aging slowed by calorie restriction: "Caloric restriction (CR) retards aging in laboratory rodents. [Little] information is available on the effects of long-term CR on physiologic markers of aging and longevity in humans. Heart rate variability (HRV) is a marker for cardiac autonomic functioning. The progressive decline in HRV with aging and the association of higher HRV with better health outcomes are well established. HRV assessment is a reliable tool by which the effects of CR on autonomic function can be assessed. Time and frequency domain analyses compared 24-hr HRV in 22 CR individuals aged 35-82 yrs and 20 age-matched controls eating Western diets (WD). The CR group was significantly leaner than the WD group. Heart rate was significantly lower, and virtually all HRV significantly higher in the CR than in the WD group. HRV in the CR individuals was comparable to published norms for healthy individuals 20 years younger. In addition, when differences in HR and HRV between CR and WD were compared with previously-published changes in HRV induced in healthy adults given atenolol, percent differences in each measure were generally similar in direction and magnitude and suggested declines in sympathetic and increases in parasympathetic modulation of HR and increased circadian variability associated with CR. These findings provide evidence that CR has direct systemic effects that counter the expected age-associated changes in autonomic function so that HRV indexes in CR individuals are similar to those of individuals 20 years younger eating WDs,"

Link: http://www.ncbi.nlm.nih.gov/pubmed/22510429

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

So very much of the research we watch is conducted in mice, rats, and - increasingly - in naked mole rats and other more esoteric members of the rodent order of mammals. Some of this work is fairly directly applicable to we humans, and some of it is not. For example, the types and proportions of advanced glycation end-product (AGE) that accumulate to damage our cells in later life are very different between rodents and humans, and so early promising work in rats aimed at developing AGE-breaker drugs to wash out these unwanted compounds translated poorly to humans.

So how much attention should we give to promising results in mice? That can only be answered for any specific case by knowing more about the use of mice in the laboratory; it is very helpful for the layperson to have a better grasp as to the benefits, limitations, and expectations held by scientists when it comes to research in rodent species that is expected to be applicable to humans. On this note, let me draw your attention to a trio of long articles from Slate that examine the humble laboratory mouse:

The Mouse Trap

Just how ubiquitous is the experimental rodent? In the hierarchy of lab animal species, the rat and mouse rule as queen and king. A recent report from the European Union counted up the vertebrates used for experiments in 2008 - that's every fish, bird, reptile, amphibian, and mammal that perished in a research setting, pretty much any animal more elaborate than a worm or fly - and found that fish and birds made up 15 percent; guinea pigs, rabbits, and hamsters contributed 5 percent; and horses, monkeys, pigs, and dogs added less than 1 percent. Taken together, lab rats and lab mice accounted for nearly all the rest - four-fifths of the 12 million animals used in total,

The Trouble With Black-6

According to one estimate, distributors like Charles River and the scientists who buy from them have created at least 400 standard, inbred strains of mouse, and 200 inbred strains of rat. Yet one stands out from the rest as the model among models in biomedicine. If you want to set up a trading post for biology, a place where researchers from around the world can exchange and compare their data, then it helps to have a common coin - a stable currency that undergirds the system. In the global marketplace of discovery, the Black-6 mouse (more formally known as the "C57BL/6") serves as the U.S. dollar.

The Anti-Mouse

As a matter of taxonomy, the naked mole rat is closer to a guinea pig or porcupine than a mouse or a rat, but really it's neither one nor the other. Buffenstein knows that she's working with an oddball; she did a lot of the work that proves it. "[The naked mole rat] does have very unique mechanisms that are not seen in other animals," she says, referring both to its superficial quirks and to whatever private biochemistry helps it to shrug off cancer, deflect toxic chemicals, ignore painful stimuli, and otherwise live five times longer than one might expect.

...

Ten years ago, Buffenstein was one of just a handful of biologists studying naked mole rats in captivity; now her field comprises some three dozen labs around the world. Her colleagues have looked at why naked mole rats are immune to the pain caused by spicy foods, or how they avoid getting itchy when doused with histamine, or what allows their brains to get by without much oxygen and a shriveled pineal gland. In Rochester, N.Y., a pair of Russian-born biologists, Andrei Seluanov and Vera Gorbunova, are devoted to finding out exactly how naked mole rats keep from getting cancer.

If you read around the warnings of doom by laboratory rodent monoculture - good news sells no papers, and the story of mice as research tools is one of great success when considered at the high level - you'll find a great deal of fascinating information. It pays to understand more about how the sausage is made when it comes to longevity research, and mice are an important part of the process. Knowing more about the limitations helps to better place the steady flow of newly announced results into context.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

We might look on aging as damage that happens as a stochastic, inevitable consequence of the operation of a biochemical system. So the buildup of chemical gunk between your cells is a part of aging, while those times you managed to break bones in your enthusiasm for life are not aging, despite the fact that what's left in the wake of those unfortunate accidents is definitely damage.

There are always special cases and grey areas worth thinking about, however. Such as teeth, for example, as I was reminded earlier today. Teeth have a pretty hard time of it, actually, when you stop to think about it. Even in this modern age our teeth maintenance technologies remain woefully inadequate in the face of bacterial species that break down enamel, and so our teeth are one of the most failure-prone and damage-prone parts of the body - and they get to the point of painful dysfunction far earlier than the rest of our organs if left to their own devices.

But that isn't aging - it's parasitism, no more aging than the consequences of contracting malaria. It's still something we need to fix, of course, and I post on this and related topics because it is of general interest to anyone who follows research into rejuvenation and regeneration. If most or all of us suffer a particular form of bacterial malfeasance that manages to be as damaging as that which chews upon our teeth, than dealing with that problem has to be included in any general toolkit for enhanced human longevity.

As an aside, I should note that the hard components of teeth do age:

enamel thickness related to age showed a steady decrease, beginning at approximately age 50.

There are apparently chemical composition changes, increased brittleness, and so forth - none of which seems to have much to do with the bacteria that cause cavities.

Another completely unrelated grey area is something I touch on frequently: the structural changes that take place in the <a href=adaptive immune system due to exposure to infectious agents. The adaptive component of the immune system performs throughout life just as it evolved to do - which means it devotes space and cells to remembering the pathogens it has encountered so that it can effectively destroy them in the future. But by continuing to function in this way, it becomes less and less effective over time: in later life too much of its capacity is taken up with memory cells and too little with killer cells. So quite aside from what we might think of as biological aging, the adaptive immune system succeeds itself into an increasingly broken state just by doing its job. Whether or not we call this process aging, it still has to be fixed, auch as by using targeted cell destruction therapies to eliminate memory cells and free up space.

There are other examples. But you get the point: not all of the degenerations that we suffer with advancing age are in fact aging per se, or at least they will not fit into the usefully narrow definitions of aging that I find helpful. They will still need to be addressed, prevented, and their consequences repaired.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

If you can build new living tissue to be implanted in patients, then why not also give it the capacity to perform additional useful tasks? This is a technology platform with some potential: "combining gene therapy with tissue engineering could avoid the need for frequent injections of recombinant drugs. Patients who rely on recombinant, protein-based drugs must often endure frequent injections, often several times a week, or intravenous therapy. Researchers [have demonstrated] the possibility that blood vessels, made from genetically engineered cells, could secrete the drug on demand directly into the bloodstream. ... Such drugs are currently made in bioreactors by engineered cells, and are very expensive to make in large amounts. ... The paradigm shift here is, 'why don't we instruct your own cells to be the factory?' ... [Researchers] provide proof-of-concept, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO). ... The researchers created the drug-secreting vessels by isolating endothelial colony-forming cells from human blood and inserting a gene instructing the cells to produce EPO. They then added mesenchymal stem cells, suspended the cells in a gel, and injected this mixture into the mice, just under the skin. The cells spontaneously formed networks of blood vessels, lined with the engineered endothelial cells. Within a week, the vessels hooked up with the animals' own vessels, releasing EPO into the bloodstream. Tests showed that the drug circulated throughout the body and reversed anemia in the mice."

Link: http://www.marketwatch.com/story/engineered-drug-secreting-blood-vessels-reverse-anemia-in-mice-2011-11-15

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http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm