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

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

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

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

No-one should be surprised by the plausibility of rejuvenation biotechnology, as old people create young children, and only a tiny hint of the damage that makes people old seeps through that process. So we know that there exist ways for cells and larger structures to extremely effectively manage their level of damage - and some of the explorers in stem cell science have already recreated these processes outside their normal context. Here is a further exploration of what happens when old animals create young animals: "Although the body is constantly replacing cells and cell constituents, damage and imperfections accumulate over time. Cleanup efforts are saved for when it really matters. ... I have a daughter. She is made of my cells yet has much less cellular damage than my cells. Why didn't she inherit my cells including the damaged proteins? That's the process I'm interested in. ... A few days after conception, the cells in the embryo all look the same - they are unspecified stem cells that can develop into any bodily cell type. As the process of cell specification (differentiation) begins, they go from being able to keep dividing infinitely to being able to do so only a limited number of times. This is when they start cleansing themselves. ... 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. ... In the past, researchers have believed that the body keeps cells involved in reproduction isolated and protected from damage. Now it has been shown that these types of cells go through a rejuvenation process that rids them of the inherited damage." Can this process be isolated and applied safely to ordinary cells elsewhere in the body? Time will tell, but it's a worthy goal to aim for given its demonstrated effectiveness.

Link: http://www.physorg.com/news/2011-09-body.html

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

One possible form of future immune therapy involves growing vast numbers of tailored immune cells, far more than would ever naturally be present in the body, and then infusing them to sweep away the target problem - cancer being an early target for this sort of approach. Here is some groundwork for these future therapies: "Adult stem cells from mice converted to antigen-specific T cells - the immune cells that fight cancer tumor cells - show promise in cancer immunotherapy and may lead to a simpler, more efficient way to use the body's immune system to fight cancer ... Tumors grow because patients lack the kind of antigen-specific T cells needed to kill the cancer. An approach called adoptive T cell immunotherapy generates the T cells outside the body, which are then used inside the body to target cancer cells. ... It is complex and expensive to expand T cell lines in the lab, so researchers have been searching for ways to simplify the process. [They] found a way to use induced pluripotent stem (iPS) cells, which are adult cells that are genetically changed to be stem cells. ... Any cell can become a stem cell. It's a very good approach to generating the antigen-specific T cells and creates an unlimited source of cells for adoptive immunotherapy. ... By inserting DNA, researchers change the mouse iPS cells into immune cells and inject them into mice with tumors. After 50 days, 100 percent of the mice in the study were still alive, compared to 55 percent of control mice, which received tumor-reactive immune cells isolated from donors."

Link: http://www.sciencedaily.com/releases/2011/09/110920111812.htm

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

Sirtuins are most likely a dead end, or more charitably a stepping stone for researchers seeking after the mechanisms that link natural variations in metabolism to natural variations in life span, especially those induced by the practice of calorie restriction. It was one of the earliest identified pieces of the puzzle, but possibly not a useful piece in the final analysis. This has become increasingly likely as an outcome over the years as meaningful results failed to emerge from drug development based on the manipulation of sirtuins. But this happens all the time: it's larger than usual news in the scientific community only, I think, because very large sums of money have moved into this line of research over the past years, and it's one of the earliest threads that might have led to drugs that modestly slowed aging.

Though I should note, as usual, that it is a massive strategic error for the research community to focus on undertaking expensive research programs that can - at best reasonable expectation - only produce a very modest slowing of aging after the usual couple of decades of work from early results to broadly available clinical application. That strategic error is, unfortunately, well entrenched and well underway. The real and important battle of the next decade is to convince the research community, on the merits of the proposal, to ditch work on metabolic manipulation in favor of SENS-like biological repair approaches that offer the possibility of actual, working, meaningful rejuvenation of the old at the end of an expensive, large-scale twenty year research program.

But back to sirtuins, which are today's news. Here are a couple of items for you from around the web:

Longevity Gene Debate Opens Trans-Atlantic Rift

the idea that sirtuins promote longevity appeals to scientists because of experiments that were started in yeast and repeated in two other standard laboratory organisms, the roundworm and the fruit fly. It is these foundation experiments that have now come under attack by David Gems and Linda Partridge, researchers on aging at University College London. In an article published Wednesday in the journal Nature, they and colleagues have re-examined experiments in which roundworms and flies, genetically manipulated to produce more sirtuin than normal, were reported to live longer. Both experiments were flawed, they say, because the worms and flies used as a control were not genetically identical to the test organisms. The London researchers report that they have repeated the experiments with proper controls and found that extra sirtuin does not, after all, make the worms or flies live longer.

Is The 'Longevity' Gene Sirtuin One Big Research Error?

And in the last decade, sirtuin has probably been one of the industry's biggest bets, ever since high levels of this protein were linked to longer, healthier lives in a variety of animals and it was suggested that they could be behind the increased longevity seen with calorie restriction (drastic restriction of calories, without malnutrition is known to increase longevity and retard age-related diseases). So how did we get here, 10 years on, concluding that it is all a mistake?

So it all goes. The bottom line for us is, however, that even if sirtuins were the key to replicating calorie restriction, they wouldn't be the basis of the future medicines of rejuvenation. Rejuvenation biotechnology can only be based on means of repairing the damage of aging, not changing metabolism a little to gently slow down aging. Other than the SENS Foundation, I don't see any research-focused organization seriously pushing this viewpoint at the present time. That's a big problem: it means that most of the money going into aging and longevity science will have little to no effect on the future of your life span: it will be going towards a continuation of the present trend that adds a small fraction of a year to the life expectancy of adults with each passing year. The newborns get a bigger fraction of a year for their measure of life expectancy at birth, but none of us reading this now are lucky enough to be that fresh to the picture. Bigger gains than this modest trend, a trend that will see us dead with only a couple of additional years to show for it if it continues as-is, will require a radical shift in the research community's strategic vision, and a focus on repair-based biotechnologies. Not surtuins, in other words, and nothing that looks much like sirtuin research either.

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

A general interest article on supercentenarians from the Sacramento Bee: "Avice Nelson Clarke paused in her recollections of her long-ago childhood in England to make a remarkable understatement. 'I've seen lots of life already,' she said. At 111, with memories spanning the horse-and-buggy age, the Space Age and the digital age, she is on the outside edge of the nation's trend toward increasing longevity. The oldest old - supercentenarians, as aging experts refer to them - remain rare: Clarke is one of four Sacramento-region residents who reported their ages as 110 or older in the 2010 U.S. census. ... The census recorded a total of 46 Californians in the supercentenarian category. Another 27 people in the Sacramento region reported their ages as 105 to 109, census figures show. While the number of centenarians has boomed in recent decades 96,000 across the country in 2010, according to the Social Security Administration, up from 37,000 only 20 years ago the nation's population of people 110 and older has remained fairly stable. ... The world's verified oldest person ever, Jeanne Calment, died in France in 1997, age 122 years and 164 days. ... Despite the world's aging population, no one's come close to that since then. That speaks to the limits of the human life span. ... Through blood tests and gene sequencing of the oldest old, scientists want to discover the secret of their extraordinary longevity ... How have they managed to live so long? We think their longevity is inherited. They have virtually nothing else in common. Some are smokers, and some never smoked. Some are drinkers, and some never drank. They don't have the same diets. But they have long-lived parents and siblings. It must be in the DNA. ... The key age is the early 80s for men and 90 for women. If you can get to that age without dementia or major heart disease or stroke, it's the idea of getting over the hump into healthy aging. ... Even so, 40 percent of the oldest old [survive] illnesses that prove fatal to others. ... Maybe they have some kind of functional reserve. The people who live the longest seem better able to deal with illness. They have a propensity to remain independent much longer than the rest of us."

Link: http://www.sacbee.com/2011/09/20/3923381/supercentenarians-the-oldest-old.html

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

A possible road to rejuvenating some portions of the declining mechanisms of tissue regeneration in the old: "The regenerative power of tissues and organs declines as we age. The modern day stem cell hypothesis of aging suggests that living organisms are as old as are its tissue specific or adult stem cells. Therefore, an understanding of the molecules and processes that enable human adult stem cells to initiate self-renewal and to divide, proliferate and then differentiate in order to rejuvenate damaged tissue might be the key to regenerative medicine and an eventual cure for many age-related diseases. ... We demonstrated that we were able to reverse the process of aging for human adult stem cells by intervening with the activity of non-protein coding RNAs originated from genomic regions once dismissed as non-functional 'genomic junk' ... adult stem cells undergo age-related damage. And when this happens, the body can't replace damaged tissue as well as it once could, leading to a host of diseases and conditions. ... The team began by hypothesizing that DNA damage in the genome of adult stem cells would look very different from age-related damage occurring in regular body cells. ... They compared freshly isolated human adult stem cells from young individuals, which can self-renew, to cells from the same individuals that were subjected to prolonged passaging in culture. This accelerated model of adult stem cell aging exhausts the regenerative capacity of the adult stem cells. Researchers looked at the changes in genomic sites that accumulate DNA damage in both groups. ... We found the majority of DNA damage and associated chromatin changes that occurred with adult stem cell aging were due to parts of the genome known as retrotransposons ... By suppressing the accumulation of toxic transcripts from retrotransposons, we were able to reverse the process of human adult stem cell aging in culture." The next step would be to look at this process in old animals, and see what happens when it is reversed.

Link: http://www.sciencedaily.com/releases/2011/09/110920163215.htm

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

I'd mentioned the book "100 Plus" a couple of weeks ago, authored by Sonia Arrison:

To my eyes, the book is essentially a fast overview of the last ten years of science, debate, important subjects, and noteworthy people in the aging research and longevity advocacy communities. ... 100 Plus is, I think, a good book to give to the average fellow in the street who would be flattened and slain by the attempt to read Aubrey de Grey and Michael Rae's Ending Aging. That book is where the meat is - but 100 Plus is a Cliff's Notes for the current state and direction of longevity science and the advocacy community supporting it. That is a useful thing: a person reading 100 Plus will wind up in roughly the same place as a casual reader of the high points of Fight Aging!

I notice that Arrison is doing the book promotion rounds with vigor. The resulting materials include a number of audio and video interviews, such as these from Changesurfer Radio:

100 Plus: The Coming Age of Longevity pt1

100 Plus: The Coming Age of Longevity pt2

Dr. J. chats with Sonia Arrison, a futurist and policy analyst who has studied the impact of new technologies for the Pacific Research Institute (PRI). They discuss her new book 100+: How the Coming Age of Longevity Will Change Everything, from Careers and Relationships to Family and Faith.

There is also official video of her presentation at the recent SENS5 conference, which you will find is posted to the conference YouTube channel, with thanks to the SENS Foundation volunteers for the time they take to make that happen:

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