From Popular Science: "Giving cardiac patients a heart of gold nanowires could ensure engineered tissue works like it should, pulsing in unison to make the heart beat. First growing nanowires and then growing heart cells, [engineers] say their new muscle-machine blended heart patch improves on existing cardiac patches, which have trouble reaching a consistent level of conductivity. ... Electrical signals shared among calcium ions dictate when cardiomyocytes contract, making the heart beat. But tissue scaffolds are often made with materials like polylactic acid or alginate, which act as insulators, so the signals are blocked. This makes it difficult to get all the cells in a piece of tissue to coordinate their signals and beat in time, which in turn makes it difficult to build a very big or very effective heart patch. The [rsearch team] gets around this problem by integrating gold, an excellent conductor. They mixed alginate, a gummy substance often used in tissue scaffolds, and grew gold nanowires throughout it. Then they seeded the alginate with cardiomyoctes from rat embryos, and monitored calcium levels to gauge their electrical conductivity. Compared to a typical scaffold system, the gold nanowire cells' conductivity improved by three orders of magnitude."

Link: http://www.popsci.com/technology/article/2011-09/heart-patch-gold-nanowire-helps-rebuild-cardiac-tissue

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

Exercise is generally beneficial to long term health in many ways - though it's somewhat cruel that it's so beneficial for the suffers of conditions that make it hard to exercise: "physical activity improves arthritis symptoms even among obese mice that continue to chow down on a high-fat diet. The insight suggests that excess weight alone isn't what causes the aches and pains of osteoarthritis, despite the long-held notion that carrying extra pounds strains the joints and leads to the inflammatory condition. ... Many cases of arthritis are associated with obesity and inactivity, so [the] researchers set out to determine whether a high fat diet induces knee osteoarthritis, and then whether exercise provides a protective effect. Using two sets of male mice - half fed a high-fat diet and the other fed regular chow - the researchers noted significant differences among the two groups. The mice on the high-fat food gained weight rapidly, processed glucose poorly and had much higher blood levels of molecules that trigger the chronic inflammation associated with osteoarthritis. But when these animals got regular running wheel workouts, many of the harmful effects diminished - even though the mice ate the same high-fat food and shed no weight. Glucose tolerance improved, while the inflammatory response was disrupted among key signaling molecules called cytokines, easing the development of arthritis. If the extra weight on the joints had been the cause of the arthritis, the researchers noted, exercise would have exacerbated the problem. Instead, it helped. ... I don't want to say exercise is turning off that inflammatory signal, it just impairs it." The fat tissue accumulated by the obese is a trigger for inflammation via chemical signaling; weight on joints may not be aggravating arthritis, but the increase to levels of chronic inflammation will do just that. Better to be both exercising and shedding the excess fat than just one or the other.

Link: http://www.eurekalert.org/pub_releases/2011-09/dumc-eea092111.php

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

Updates to the Fight Aging! site tend to come in waves, as and when my time frees up sufficiently between the ebb and flow of other projects. The next wave isn't here yet, but will be, so I thought I'd solicit opinions. By all means add yours in the comments to this post.

One thing I hear a lot of is the request for like/share buttons for Facebook, Twitter, and so on - that won't be happening. I've performed this experiment already (you might recall that the previous design included sharing buttons) and the difference between having them and not having them in terms of engagement, new visitors, and overall traffic was minimal. On the other hand, they definitely slowed down page load time and made the site that little bit more ugly into the bargain. More importantly, they tracked visitors, adding to the growing databases that will be used for whatever purposes that the social sites will come up with the future; I'm not of the mindset to help them with the construction of their panopticon foundations at the expense of visitors to my little corner of the web. So on the whole I'm happy to force on you the modest make-work of cutting and pasting the URL you wish to share with your friends - and for a little more make-work you could even arrange matters for your browser to insert a share button regardless of what I do. Ultimately the web page transmitted to you by a server is no more than a suggestion as to what you should actually view: with the proper tools you can rearrange web pages on the fly before they are presented to you.

Another reason to skip the share buttons is that many of them deliver what I would regard as worthless traffic. StumbleUpon is particularly bad in this respect: my logs are full of people turning up from that site, arriving at a long and interesting post, and leaving after a few seconds. Hundreds upon hundreds of them, every day. StumbleUpon is, in some of its incarnations, a channel-surfing engine with infinite channels; people click the button and only stop if something catches their eye in a faction of a second. Next to nothing here will do that, and these are not people likely to be engaged by the Fight Aging! message. I lose nothing by failing to cultivate that traffic.

(The Google Analytics script that still runs on the site will no doubt eventually succumb to the frame of mind outlined in the paragraphs above, but for now it at least somewhat anonymizes your IP address and is fairly easily blocked).

Other suggestions fall into the bucket of fleshing out the functionality: making the site more portal-like at their grandest, such as by adding forums, most popular or most commented lists in the sidebar, more and more varied content, and so on. The less grand suggestions are tweaks to functionality to provide features seen on other tech news and essay sites, or minor additions to content, such as to stop displaying the full text of each post on the home page, enabling visitors to post links to relevant content more easily, adding a list of journals to the resources section, make the comment section more apparent. Thing of that ilk.

Some of these I agree with, some of them I don't. I should explain that Fight Aging! is something of a hybrid of two functions in its present structure. Firstly, it has some pretensions to being a stream of fresh content: a news and opinions site that is relevant to aging research and longevity science. In this it is little different from most blogs and newsletters: we all understand roughly how these things work. They care about the traffic of the now, and comparatively little for their archives, so they tend to become involved in a race for the bottom in gathering attention and being first - quality and correctness come a distant second, and they measure success by page views because that's what drives their revenues. I've never been particularly interested in playing that game. It's useful and, I think, necessary to have a modest flow of new content in order to continue to be relevant as an item of interest in your community, but that's all that's needed: enough to remain relevant so that people will listen when you have something to say.

So much of what you see on revenue-generating news and blog sites is inappropriate or not terribly useful for Fight Aging! The share buttons are a good example: if an item is there for the purposes of accelerating the race to the bottom of the pool of shallow attention, then I don't need it. I'd argue that shallow attention doesn't get you anywhere in the business of advocacy to grow a small community with big, complex ideas, such as the present longevity science community. What you need is engaged, quality attention. It is my belief that shallow attention only becomes useful, or at least convertible into results such as funding or labor, when you have a massive community and you're trying to gain a popular consensus of some sort among the public at large.

The second function of Fight Aging! is to act as a beacon and resource for people who are on the verge: interested enough to look into life extension, aging, and rejuvenation biotechnology, but neither connected nor particularly aware of the community. When they stumble over Fight Aging! in searches, I see that as a chance to inform and educate. So I place a great deal more value on the Fight Aging! archives than I would if this were only a standard issue blog or news site, and the fact that pages in those archives are littered with links to more general and introductory content is important.

So when I think about what should be done in the next wave of alterations to Fight Aging!, I am thinking in terms of advocacy and growth, which may map in some way to the web traffic I see here, but which is definitely not the same as a straight measure of traffic or engagement or any other metric easily chased. In terms of expansion versus focus, I'm presently more in favor of focus: it would be good to narrow down to look at the things that work and see about how to make them more useful, more functional, more widely used, more influential. For example, it's been a while since I've seriously looked at how I might improve the Fight Aging! newsletter or broaden its reach, despite the fact that it has thousands of subscribers. The same goes for the RSS feeds, which have a presently unknown reach and utilization.

On the expansion side, it's not that I'm not in favor of big glittering longevity science web portals, but that I don't think the community is large enough to support such a thing at this point in time. It's my impression that the present longevity science community - people who are interested enough to be a part of the discussion, or who are in the research community, or who are donating funds, and so forth - is at the size sufficient for an active web forum or two and a couple of mailing lists and newsletters. I think that because that number of forums, mailing lists, and newsletters is pretty much what has emerged organically. If there was the interest and the headcount for more than that, then it would already exist; there are any number of people out there whose business is to sniff out new communities and launch websites to serve them news before anyone else does, and they are largely absent - or worse than absent, off servicing the "anti-aging" marketplace instead, as there's real money over there. This is unfortunate, and we'd all like matters to be further along, but it is what it is, or at least until we help it bootstrap into something more.

In any case, to return to the original point, there will be time for some updates and change ahead - make your preferences known now or forever hold your peace.

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

Via ScienceDaily: researchers "have identified more than 70 genes that play a role in regenerating nerves after injury, providing biomedical researchers with a valuable set of genetic leads for use in developing therapies to repair spinal cord injuries and other common kinds of nerve damage such as stroke. ... the scientists detail their discoveries after an exhaustive two-year investigation of 654 genes suspected to be involved in regulating the growth of axons - the thread-like extensions of nerve cells that transmit electrical impulses to other nerve cells. ... We don't know much about how axons re-grow after they're damaged. When you have an injury to your spinal cord or you have a stroke you cause a lot of damage to your axons. And in your brain or spinal cord, regeneration is very inefficient. That's why spinal cord injuries are basically untreatable. ... While scientists in recent decades have gained a good understanding of how nerve cells, or neurons, develop their connections in the developing embryo, much less is known about how adult animals and humans repair - or fail to repair - those connections when axons are damaged. ... Of particular interest [are] the six genes that appear to repress the growth of axons. ... The discovery of these inhibitors is probably the most exciting finding [because] identifying and eliminating the inhibiting factors to the re-growth of axons could be just as essential as the biochemical pathways that promote axon re-growth in repairing spinal cord injuries and other kinds of nerve damage."

Link: http://www.sciencedaily.com/releases/2011/09/110921144604.htm

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

I see that Maria Konovalenko has posted notes on a few of the presentations on longevity science given at SENS5:

Dr. Laura Niklasson from Yale University is working on lung engineering. Human lung is an extremely complicated organ. There's 23 generations of branching of airways, they are up to 200 microns in diameter. 70 square meters for gas exchange. More than 100 million air sacks all together. Engineered lung must have right mechanical properties, autologous cells, adequate surface area for gas exchange and adequate barrier to prevent flooding of airways with blood constituents after implantation. ... Scientists implanted engineered half lung in a rat. It was 95% as efficient as a native lung in terms of gas exchange. But in several hours they got thrombosis. Also they saw a little bit of blood cells in airways, so the barrier was not perfect. After being improved this technique can be used to engineering human lungs.

...

John Jackson gave a beautiful overview of thymic involution and told us about the ongoing experiments in the Wake Forest Institute for Regenerative Medicine on thymus engineering.

...

I personally found the talk by Dr. Charles Greer the most fascinating one. Aparently, there is a subsytem in our brain that is constantly regenerating. The rate and quality of this regeneration process doesn't decline with age. It's the olfactory system. Sensory neurons in olfactory system die every 6-8 weeks. Neurogenesis is constant. New neurons come from the subventricular zone. It's like a river of migrating neurons to olfactory bulb.

Meanwhile, the SENS Foundation volunteers are steadily uploading conference video to a YouTube channel - the John Jackson presentation on tissue engineering for the thymus is amongst those already available:

You might also find the following presentation to be of interest. It's a part of the broader LysoSENS program, which involves finding ways to safely remove the age-related build up of various damaging metabolic byproducts and other chemicals that our cellular recycling mechanisms normally struggle with. One of these compounds is 7-ketocholesterol:

7-ketocholesterol (7KC) is a cytotoxic oxysterol that plays a role in many age-related degenerative diseases. 7KC formation and accumulation occur in the lysosomes in a number of cell types, hindering enzymatic transformation, and increasing the chance for lysosomal membrane permeabilization.

We assayed the potential to mitigate 7KC cytotoxicity and enhance cell viability by transiently transfecting human fibroblasts to overexpress several 7KC-active enzymes. One of our engineered constructs, a lysosomally-targeted cholesterol oxidase that lacked isomerization activity, significantly increased cell viability

Orchestrated by the SENS Foundation, progress is slowly being made in developing the roots of what probably at first be drugs, designed molecules - possibly attached to targeting mechanisms like tailored nanoparticles - that either break down 7-ketcholesterol and other varied harmful compounds we'd be better off without or instruct the cell itself to better perform that task. The only thing stopping that progress from being faster is a lack of large-scale funding.

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

The aging of the human adaptive immune system takes and interesting and distinct form when compared with the aging of other organs and processes. There is accumulating cellular damage, yes, but there is also a very important and ongoing process of misconfiguration: an otherwise largely sound system ceasing to function correctly not because it is damaged per se, but because it becomes poorly organized. That is, potentially, a much easier problem to solve than many of the other challenges presented to us by aging.

The way in which this misconfiguration happens is described back in the Fight Aging! archives. The short version is that the adaptive immune system remembers all threats, but has a limit to the number of cells it can produce; eventually too much of its quota is taken up by memory cells and too little by cells that are actually equipped to destroy things. A small range of persistent but otherwise mostly harmless viruses, such as cytomegalovirus (CMV), greatly speed up this process by hanging around for decades and constantly provoking the immune system into uselessly devoting ever more memory cells to their existence.

There are a range of possible ways to deal with this issue, with varying levels of complexity, cost, and permanence: adding more cells cultured from the patient's own stem cells, destroying the unwanted memory cells using targeted therapies of the sort under development in the cancer research community, and so forth. One of the presentations given at the SENS5 conference discusses the latest research in this area:

Aging is associated with an increased susceptibility of older individuals to new and emerging infections; poor responses to vaccination compound this vulnerability. ... In both mouse and man, repeated interactions between reactivating viruses such as CMV and antiviral T cells leads to memory T-cell inflation (MI) with increasing accumulation of these cells over the lifespan. It was hypothesized that MI may exact a price for the immune system: competition between inflating, CMV-specific memory T-cells and naive T-cells supposed to defend against all other infections may impair the maintenance of a diverse naive T-cell pool, consequently leaving the individual at a disadvantage when exposed to a new pathogen. We have directly tested this hypothesis using a mouse model of lifelong persistent infection.

There is also video of the presentation, which I think you'll find interesting - the research community is clearly within striking distance of a range of novel and effective repair methodologies for immune system aging:

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

You might have noticed recent investigations into exactly how embryos generated by an old collection of cells - people like you and I - turn out to be made of young cells. After all, every other clump of cells we generate is also old.

Quite unexpectedly we found that the level of protein damage was relatively high in the embryo's unspecified cells, but then it decreased dramatically. A few days after the onset of cell differentiation, the protein damage level had gone down by 80-90 percent. We think this is a result of the damaged material being broken down.

If we're lucky there's a potent life-extending therapy in there somewhere, but of course the odds are good that the process by which the early embryo repairs most of its damage is tightly bound to the embryonic nature of its cellular machinery and will be somewhere between very challenging and next to impossible to safely apply to organized, differentiated structures of adult cells. The difference between "very challenging" and "next to impossible" is probably about twenty years of technological development in this era - but we shall see. This seems worth watching.

The researchers involved in this latest research into embryonic development think that the proteasome is the root of this profound embryonic damage repair process. This is a recycling mechanism in the cell that is separate and distinct from the lysosome that regular readers are probably sick of hearing about by now, focused on breaking down every errant protein that looks like it doesn't belong, is unwanted, or is somehow malfunctioning.

The rate of accumulation of damaged proteins and larger cellular components is important in determining the pace of aging, and this is illustrated by the degree to which the recycling processes of autophagy keeps turning up in investigations of various longevity-enhancing mutations and environmental circumstances. If a machine accumulates gunk and broken parts, then it tends to break down more rapidly and in more ways - and we are in effect very complex machines. Aging is damage. This model is somewhat complicated by the fact that we can repair ourselves, by those repair mechanisms - like the proteasome and lysosome - are also machines, and prone to damage. Once the spiral down starts it tends to accelerate, and eventually you wind up with the aptly named garbage catastrophe view of aging.

But here is an example of quite different research into aging and the activities of the proteasome - in yeast rather than people. Yet it still shows that, as for other forms of recycling mechanism, healthy life span lengthens as these cellular maintenance tool kits work harder.

Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae

The ubiquitin/proteasome system (UPS) is an integral part of the machinery that maintains cellular protein homeostasis and represents the major pathway for specific protein degradation in the cytoplasm and nuclei of eukaryotic cells. Its proteolytic capacity declines with age. In parallel, substrate load for the UPS increases in aging cells due to accumulated protein damage. This imbalance is thought to be an origin for the frequently observed accumulation of protein aggregates in aged cells and is thought to contribute to age-related cellular dysfunction.

In this study, we investigated the impact of proteasome capacity on replicative lifespan in Saccharomyces cerevisiae using a genetic system that allows manipulation of UPS abundance at the transcriptional level. The results obtained reveal a positive correlation between proteasome capacity and longevity, with reduced lifespan in cells with low proteasome abundance or activity and strong lifespan extension upon up-regulation of the UPS in a mechanism that is at least partially independent of known yeast longevity modulating pathways.

All told, the longevity science community hasn't devoted as much attention to the proteasome as to other housekeeping mechanisms, but that will probably change in the years ahead. All it takes is one widely noticed mouse study with an impact on aging to generate a great deal more attention.

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

From In the Pipeline: "I'd say that the whole sirtuin story has split into two huge arguments: (1) arguments about the sirtuin genes and enzymes themselves, and (2) arguments about the compounds used to investigate them, starting with resveratrol and going through the various sirtuin activators reported by Sirtris, both before and after their (costly) acquisition by GlaxoSmithKline. That division gets a bit blurry, since it's often those compounds that have been used to try to unravel the roles of the sirtuin enzymes, but there are ways to separate the controversies. I've followed the twists and turns of argument #2, and it has had plenty of those. It's not safe to summarize, but if I had to, I'd say that the closest thing to a current consensus is that (1) resveratrol is a completely unsuitable molecule as an example of a clean sirtuin activator, (2) the earlier literature on sirtuin activation assays is now superseded, because of some fundamental problems with the assay techniques, and (3) agreement has not been reached on what compounds are suitable sirtuin activators, and what their effects are in vivo. It's a mess, in other words. But what about argument #1, the more fundamental one about what sirtuins are in the first place? That's what these latest results address, and boy, do they ever not clear things up. There has been persistent talk in the field that the original model-organism life extension effects were difficult to reproduce, and now two groups (those of David Gems and Linda Partridge) at University College, London (whose labs I most likely walked past last week) have re-examined these. They find, on close inspection, that they cannot reproduce them. ... It's important to keep in mind that these aren't the first results of this kind. Others had reported problems with sirtuin effects on lifespan (or sirtuin ties to caloric restriction effects) in yeast, and as mentioned, this had been the stuff of talk in the field for some time. But now it's all out on the table, a direct challenge."

Link: http://pipeline.corante.com/archives/2011/09/22/the_latest_sirtuin_controversy.php

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

Via ScienceDaily, an example of the sometimes indirect way in which stem cell transplants can cause benefits: "Acute lung injury is brought on by a number of conditions, such as pneumonia and sepsis, also known as blood poisoning. In some cases, acute lung injury develops into a more serious condition, known as acute respiratory distress syndrome, and results in insufficient oxygenation of blood and eventual organ failure. ... inflammation due to injury or infection can make the border of epithelial cells become more porous than it should be. The increased permeability allows an often-deadly mix of substances, such as fluid and cells, to seep into and accumulate in the alveoli. ... The team decided to re-create the unhealthy lung conditions in the lab - by culturing human alveolar cells and then chemically causing inflammation - and to observe how the presence of bone marrow stem cells would change things. ... We then introduced mesenchymal stem cells without direct cell contact, and they churned out a lot of protein, called angiopoietin-1, which prevented the increase in lung epithelial permeability after the inflammatory injury ... [researchers] hope clinical trials will prove the therapy is a viable one for preventing respiratory failure in critically ill patients."

View the Article Under Discussion: http://www.sciencedaily.com/releases/2010/08/100811162352.htm

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

Researchers continue to put induced pluripotent stem cells (iPSCs) through their paces: "iPSCs, discovered in 2006, are derived by reprogramming adult cells into a primitive stem cell state. They are similar to [embryonic stem cells (ESCs)] in terms of their ability to differentiate into different types of cells in vivo, including endoderm cells that give rise to liver and lung tissue. ... induced pluripotent stem cells (iPSCs) can differentiate into definitive endoderm cells, in vitro, with similar functional potential when compared to embryonic stem cells (ESCs), despite minor molecular differences between the two cell types. These findings are particularly important given growing controversy in the scientific literature about whether subtle differences between iPSCs and ESCs should dampen enthusiasm for iPSCs to serve as an alternative source of differentiated precursor cells for various tissues, such as the liver, lung or blood. The new work provides compelling evidence that iPSCs have potential in regenerative medicine as an investigational tool for the development of treatments against diseases that affect endodermal-derived organs, such as cirrhosis, diabetes, cystic fibrosis and emphysema."

Link: http://www.medicalnewstoday.com/articles/223994.php

For a variety of reasons lung tissue engineering has lagged behind foundational work on other organs - but there are signs that it is catching up: researchers "have identified a human lung stem cell that is self-renewing and capable of forming and integrating multiple biological structures of the lung including bronchioles, alveoli and pulmonary vessels. ... This research describes, for the first time, a true human lung stem cell. The discovery of this stem cell has the potential to offer those who suffer from chronic lung diseases a totally novel treatment option by regenerating or repairing damaged areas of the lung ... Using lung tissue from surgical samples, researchers identified and isolated the human lung stem cell and tested the functionality of the stem cell both in vitro and in vivo. Once the stem cell was isolated, researchers demonstrated in vitro that the cell was capable of dividing both into new stem cells and also into cells that would grow into various types of lung tissue. Next, researchers injected the stem cell into mice with damaged lungs. The injected stem cells differentiated into new bronchioles, alveoli and pulmonary vessel cells which not only formed new lung tissue, but also integrated structurally to the existing lung tissue in the mice."

Link: http://www.eurekalert.org/pub_releases/2011-05/bawh-hls051011.php

What is your proteome? In short, it is the list of all the proteins built within your body and their abundance - a parts catalog for your biological machinery. Analysis of even modest fractions of the proteome has only recently become practical, but it is potentially a good way to measure the complexity of repairing and reversing aging, or gain insight into which contributing mechanisms of aging are the most important. Aging is no more than change: damaged proteins, unwanted molecules, things in the wrong place at the molecular level - which leads to malfunction and failure in the large-scale organs and processes of the body.

The good news for today is that a comparison of young and old proteomes in mice shows that there is little change with aging. This is a positive result for the future of longevity science, because it means researchers can rapidly follow up on the few changes that were identified. The opposite result - many changes, as is the case for gene expression - would have been rather discouraging: a sign that matters are very complex in yet another area of the biology of aging, and that much work would have to take place in order to understand the relevance of the data.

From the open access paper (for the full paper, you'll want the PDF version):

The biological process of aging is believed to be the result of an accumulation of cellular damage to biomolecules. While there are numerous studies addressing mutation frequencies, morphological or transcriptional changes in aging mammalian tissues, few have measured global changes at the protein level. Here, we present an in depth proteomic analysis of three brain regions as well as heart and kidney in mice aged 5 or 26 months.

...

In frontal cortex and hippocampal regions of the brain, more than 4,200 proteins were quantitatively compared between age groups. Proteome differences between individual mice were observable within and between age groups. However, mean protein abundance changes of more than two-fold between young and old mice were detected in less than 1% of all proteins and very few of these were statistically significant. Similar outcomes were obtained when comparing cerebellum, heart and kidney between age groups. Thus, unexpectedly, our results indicate that aging-related effects on the tissue proteome composition at the bulk level are only minor and that protein homeostasis remains functional up to a relatively high age.

It is unexpected, given the gene expression findings to date - but welcome. I look forward to seeing the results from human studies. Given the free-falling cost of bioinformatics, and commensurate improvement in the technology, comparing proteomes in young and old people will be a graduate student project within a handful of years.

Microglia are immune cells that defend and clean up the brain and spinal cord. Like the rest of the immune system, they progressively fail in their work with age. Worse, like other immune system components, they begin to become actively harmful by causing chronic inflammation and other forms of damage instead of helping. Reversing that trend is one important line of research among many that, as they produce working medical technologies, will extend our healthy life spans.

Keeping the brain in good working shape is one of the most important goals of medical research. There is no short cut here by way of the comparatively advanced fields of stem cell medicine and tissue engineering - we can't look ahead to replacement brains in the next decade or two as we can for other organs. The brain has to be repaired in situ, completely and sufficiently for the long term: every form of age-related cellular damage either worked around or reversed. So microglia, as an important part of the existing maintenance systems in the brain, are of considerable interest. Can early successes be obtained by boosting their activity, or slowing or reversing their decline with age? The Longecity-funded research project on microglia transplants falls into this general area of research - something we'd like to see more of.

Following on from that topic, here is an open access review paper that provides an introduction to microglia in context of aging and neurodegeneration:

For many years, chronic neurodegenerative disorders of the central nervous system (CNS) were thought of in terms of primary neuronal dysfunction and loss with secondary glial and inflammatory responses. ... but of late this theory has required revision.

Microglia, which account for approximately 10% of the adult brain cell population, were first described by Pio Del Rio Hortega in 1919 ... However, it was not until the late 1980s that this field came of age when, using the new technique of immunohistochemistry, the McGeers showed that within the Alzheimer's disease (AD) brain there were large numbers of [activated] microglia. ... The pioneering work of the McGeers was to radically change how these diseases were seen as they went on to show that microglia were not only intimately bound to central inflammatory responses and antigen presentation, but in fact the whole innate immune system itself had a role to play in these CNS disorders.

Initial views on the role of microglia suggested that these cells were simply there to scavenge up debris and dead cells, while astrocytes fulfilled some supportive role in the CNS. However, microglia are now recognized to have a complex array of supportive and destructive roles in the CNS and that the balance between the two may be critical in driving some aspects of disease processes. Astrocytes are now seen as being fundamental in shaping and maintaining the developing and mature CNS, including a role in adult neurogenesis, axonal regeneration, and the [blood-brain barrier]. The dynamic interplay between all of these different CNS compartments is becoming more evident, such that some neurodegenerative disorders of the CNS may have a pathology as much in the glial cells as in the neurons themselves. This all means that understanding what happens in disease states is far more complex than originally conceived and that targeting each element of the interaction may be the route by which true disease modification can be achieved.

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

The SENS Foundation Academic Initiative continues to grow, laying the foundation for the next generation of researchers working on rejuvenation biotechnology: "The Academic Initiative is likely to see another increased budget in 2013. We plan to offer at least as many scholarships and grants as we're offering this year, while we are nearly certain to expand our summer internship program, bringing in more interns overall and sending them to a greater number of labs. This year, some interns have been placed at the SENS Foundation Research Center, while others have gone to the Buck Institute for Research on Aging. We hope to place more interns at each location next year, and to add new locations. The Initiative's budget may not be the only thing that changes with the coming of the new year. SENS Foundation itself is still planning a revamp of its website, and the Academic Initiative won't miss that chance to have its own website enhanced further. Planning for our own next website has begun: long story short, it'll be simpler with less text and will offer very clear and immediate ways for students to get started. Some graphic design work that will go online with that new site is also underway. We'd like to finish by pointing out that we still have enough funding to continue to award materials grants throughout the summer and into the Fall 2012 semester. Since many students have extra time to put a proposal together over the summer, and since we're currently seeing a (likely summer-related) increase in interest in our grants, this is a particularly good time to apply."

Link: http://sens.org/node/2762

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

Here is a study that points to amount of visceral fat as a dominant contribution to the risk of age-related type-2 diabetes - a condition rarely suffered by people who successfully avoid putting on weight over the years - something that doesn't just happen, but requires exercise and a sensible approach to diet and lifestyle. "A collaborative re-analysis of data from the InterAct case-control study [has] established that waist circumference is associated with risk of type 2 diabetes, independently of body mass index (BMI). Reporting in this week's PLoS Medicine, the researchers estimated the association of BMI and waist circumference with type 2 diabetes from measurements of weight, height and waist circumference, finding that both BMI and waist circumference were independently associated with type 2 diabetes risk but waist circumference was a stronger risk factor in women than in men. ... The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident [type 2 diabetes] cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. ... These findings indicate that targeted measurement of waist circumference in overweight individuals (who now account for a third of the US and UK adult population) could be an effective strategy for the prevention of diabetes because it would allow the identification of a high-risk subgroup of people who might benefit from individualised lifestyle advice. ... Our results clearly show the value that measurement of [waist circumference] may have in identifying which people among the large population of overweight individuals are at highest risk of diabetes." A risk that is essentially yours to create, remove, or manage through the choices you make.

Link: http://www.eurekalert.org/pub_releases/2012-06/plos-wcl053112.php

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

An update on the LysoSENS research project from the SENS Foundation, which aims to discover and adapt bacterial enzymes to break down the damaging buildup of unwanted metabolic byproducts in the aging body: "SENS Foundation-funded research shows that expression of a modified microbial enzyme protects human cells against 7-ketocholesterol toxicity, advancing research toward remediation of the foam cell and rejuvenation of the atherosclerotic artery. ... Atherosclerotic cardiovascular disease is the principal cause of ischaemic heart disease, cerebrovascular disease, and peripheral vascular disease, making it the root of the leading cause of morbidity and mortality worldwide. Atherosclerosis begins with the entrapment and oxidation of low-density lipoprotein (LDL) cholesterol in the arterial endothelium. As a protective response, the endothelium recruits blood monocytes into the arterial wall, which differentiate and mature into active macrophages and engulf toxic oxidized cholesterol products (oxysterols) such as 7-ketocholesterol (7-KC). Although initially protective, this response ultimately leads to atherosclerotic plaque: oxidized cholesterol products accumulate in the macrophage lysosome, and impair the processing and trafficking of native cholesterol and other materials, leading macrophages to become dysfunctional and immobilized ... more and more of these disabled "foam cells" progressively accumulate in the arterial wall, generating the fatty streaks that form the basis of the atherosclerotic lesion. Rejuvenation biotechnology can be brought to bear against this disease of aging through the identification, modification, and therapeutic delivery of novel lysosomal enzymes derived from microbes to the arterial macrophage - enzymes which are capable of degrading oxidized cholesterol products. SENS Foundation-funded researchers have been making steady progress in the identification and characterization of candidate enzymes for several years now, and a new report represents a substantial advance in the research: the rescue of cellular oxysterol toxicity by an introduced microbial lysosomal enzyme."

Link: http://sens.org/node/2737

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

Maria Konovalenko of the Science for Life Extension Foundation here reports on the recent Genetics of Aging and Longevity Conference, held last month in Moscow and attracting researchers in the field from around the world.

It has been a while since I've posted my blog updates. The reason was the Genetics of Aging and Longevity conference. I have been involved in preparations of this meeting since December and the last month before the event was especially tough. Anyway, the conference turned out to be pretty good. I was surprised to hear so many good responses and impressions from the attendees and the speakers, so I am proud to say that the meeting was a success. The talks were superb, a lot of new and even unpublished data, a lot of discussions during the breaks and meals. I saw quite many people walking around with burning eyes - from excitement of science, of course) Some of those eyes are in the photos below. I believe this was a ground braking event on life extension topic in Russia, a truly unique gathering of minds. The more meetings like this we have, the more attention they get in the media, the better chances we have to live longer.

The post includes a great many photographs of folk from the aging research community; browse through if you are interested in putting faces to the names you read about in the science press. Konovalenko concludes with this note:

Quite a lot of researchers said that we are on the verge of a breakthrough in the area of life extension. Maybe we have already discovered something fantastic, but haven't yet realized it'd effective for people. Even if we have a drug that slows aging down, we still need a panel of biomarkers to prove the effect. I do hope we will have both the breakthrough and the markers soon.

I'll point you to something I said a while back about concrete and conferences:

I'm a fan of the "concrete and conferences" metric for measuring the health of science. Two side effects of increasing research funding in a field are new buildings at universities and research centers (the "concrete" part of the metric) and new gatherings of researchers (the conferences). Both of these symptoms are also fairly easy to track. The more of both, the better, with new buildings indicating more money entering the system than new conferences.

More conferences generally indicates a larger population of researchers with budgets, interest in the field, and progress in their laboratories to talk about.

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

Researchers are working on creating regeneration in mammals where it does not normally happen: "Researchers have long tried to get the optic nerve to regenerate when injured, with some success, but no one has been able to demonstrate recovery of vision. A team [now] reports a three-pronged intervention that not only got optic nerve fibers to grow the full length of the visual pathway (from retina to the visual areas of the brain), but also restored some basic elements of vision in live mice. ... [the mice were able to] regain some depth perception, the ability to detect overall movement of the visual field, and perceive light. ... Previous studies [have] demonstrated that optic nerve fibers can regenerate some distance through the optic nerve, but this is the first study to show that these fibers can be made to grow long enough to go from eye to brain, that they are wrapped in the conducting 'insulation' known as myelin, that they can navigate to the proper visual centers in the brain, and that they make connections (synapses) with other neurons, allowing visual circuits to re-form. ... [Researchers] combined three methods of activating the growth state of neurons in the retina, known as retinal ganglion cells: stimulating a growth-promoting compound called oncomodulin, [elevating] levels of cyclic adenosine monophosphate (cAMP) and deleting the gene that encodes the enzyme PTEN. ... these interventions have a synergistic effect on growth of optic nerve fibers. ... The eye turns out to be a feasible place to do gene therapy. The viruses used to introduce various genes into nerve cells mostly remain in the eye. Retinal ganglion cells are easily targetable."

Link: http://medicalxpress.com/news/2012-05-scientists-regenerate-optic-nerve-components.html

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

The Volokh Conspiracy on the correlations between health and wealth in a region, a connection with compelling evidence both before and after the Industrial Revolution: "for most of history, gains in human life expectancy were made at the beginning, not the end of life. It is true that older people have always been part of society, but they were less numerous and more weathered than today's seniors. ... But that is not the end of the story. Rather, it is the beginning of a new chapter where humanity takes on ill health and death at later ages. Indeed, those efforts have already had an impact on the growth of life expectancy. ... For many years, it's been clear that there is a positive correlation between health and wealth, but it was most commonly thought that wealth creates health. While it is certainly true that the rich can afford to take better care of themselves, it is now known that health also begets wealth. Put another way, poor health causes a decline in productivity for the simple reason that it's very difficult to work effectively when you're in ill health, thereby increasing the chances of falling into poverty. ... based on the available research, if there are 'two countries that are identical in all respects, except that one has a 5 year advantage in life expectancy,' then the 'real income per capita in the healthier country will grow 0.3-0.5% per year faster than in its less healthy counterpart.' While these percentages might look small, they are actually quite significant, especially when one considers that between the years of 1965 to 1990, countries experienced an average per capita income growth of 2% per year. When countries only have an average growth of 2%, an advantage of 0.5% is quite the boost. Now, those numbers are based only on a 5 year longevity advantage. What if a country had a 10, 20, or 30 year advantage? The growth may not continue on a linear basis, but if the general rule holds - a jump in life expectancy causes an increase in economic growth per capita - then having a longer-lived population would facilitate enormous differences in economic prosperity."

Link: http://volokh.com/2011/10/04/healthier-and-wealthier/

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