From Next Big Future: "The [SENS5] conference itself was high quality - many of the scientists that I describe in my book, 100+, were there. Hearing about the tangible progress that these researchers are continually making was very exciting. I noticed that there were many companies that attended this conference, which is an indication that extending health span is a prospect which is starting to garner serious consideration. ... There are a large and growing number of corporations which, although not explicitly focused on anti-aging, are developing treatments and drugs related to longevity. Gene therapy and personalized medicine are the future, and these companies know that. ... The field of regenerative medicine is getting substantial resources. That includes tissue engineering, which is essentially growing organs. The recent successes with growing and implanting human tracheas are exciting. ... The most common concern is that increased life spans will lead to overpopulation. This fear rests on the false Malthusian idea that population grows faster than our ability to provide for ourselves. We haven't run out of resources as population has grown because humans are a resource themselves, providing problem-solving ideas. Also, fertility and world population growth rates are on the decline. ... Perceptions [of longevity science] have changed. The term health extension is actually less controversial than life extension, since everyone wants robust health. There is little resistance to treatments designed to keep people healthy."

Link: http://nextbigfuture.com/2011/10/is-longevity-research-speeding-up.html

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

Sequencing of the genome of the long-lived naked mole rat was announced earlier this year, but here's more: "Scientists have sequenced the complete genome of the naked mole rat, a pivotal step to understanding the animal's extraordinarily long life and good health. A colony of more than 2,000 naked mole rats at The University of Texas Health Science Center at San Antonio contributed to the findings ... If we understand which genes are different or are expressed differently in naked mole rats - compared to short-lived mice that clearly have poor defenses against aging and cancer - we might find clues as to why the naked mole rat is able to extend both health span and longevity, as well as fight cancer, and this information could be directly relevant and translatable to humans. ... The mouse-sized naked mole rat is the longest-lived rodent known, surviving up to 31 years in captivity. This is much longer than its laboratory rodent relatives, and the naked mole rat maintains good health and reproductive potential well into its third decade. Naked mole rats live underground in large family groups, like termites and bees, with only a single breeding female. These social rodents are extremely tolerant of life in low oxygen and high levels of carbon dioxide."

Link: http://www.eurekalert.org/pub_releases/2011-10/uoth-big101211.php

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

Via EurekAlert!: "As a person ages, the ability of their beta cells to divide and make new beta cells declines. By the time children reach the age of 10 to 12 years, the ability of their insulin-producing cells to replicate greatly diminishes. If these cells, called beta cells, are destroyed - as they are in type 1 diabetes - treatment with the hormone insulin becomes essential to regulate blood glucose levels and get energy from food. Now, [researchers] have identified a pathway responsible for this age-related decline, and have shown that they can tweak it to get older beta cells to act young again - and start dividing. ... a protein called PDGF, or platelet derived growth factor, and its receptor send beta cells signals to start dividing via an intricate pathway that controls the levels of two proteins in the beta cell nucleus, where cell division occurs. Working with young mice, [researchers] found that PDGF binds to its receptor on the beta cell's surface and controls the level of these regulating proteins allowing cells to divide. However, in older mice, they discovered that beta cells lose PDGF receptors, and that this age-related change prevents beta cells from dividing. [Researchers] further found that by artificially increasing the number of PDGF receptors, they can restore the ability of the beta cell to divide and generate new cells. ... By understanding what genes are turned on and off in a young beta cell, we can try to recreate that genetic environment in older beta cells such that they divide in a desirable, controlled manner."

Link: http://www.eurekalert.org/pub_releases/2011-10/jdrf-rmo101211.php

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

An accumulation of advanced glycation endproducts (AGEs) is one of the changes thought to be a root cause of aging. The research quoted below is only a correlation, but there is plenty more where this came from to back up the viewpoint of AGEs as a contributing cause of aging: "Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. ... We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. ... Older adults with high pentosidine level had worse baseline DSST score but not different 3MS score. On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile ... [Thus] high peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21900628

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

Following on from an earlier consideration of state of the mind and how that may interact with the operation of metabolism over the long term to affect aging, here is a very readable open access paper that tries to draw lines between longevity, psychological factors, and mitochondrial biochemistry: "A central question concerning longevity remains: Why do some people live long whereas others die early? Another equally critical question concerns morbidity: Why is aging associated with a greater incidence of almost every categorized disease - including degenerative, metabolic, and malignant disorders? Since disease incidence, mortality, and longevity are all associated terms in the same aging equation, a more general question may be posed: What are the pathways that impact individuals' rate of aging? ... Compelling evidence suggests that both biological and psychosocial factors impact the process of aging. However, our understanding of the dynamic interplay among biological and psychosocial factors across the life course is still fragmentary. For example, it needs to be established how the interaction of individual factors (e.g., genetic and epigenetic endowment and personality), behavioral factors (e.g., physical activity, diet, and stress management), and psychosocial experiences (e.g., social support, well-being, socioeconomic status, and marriage) in perinatal, childhood, and adulthood influence health across the aging continuum. This paper aims to outline potential intersection points serving as an interface between biological and psychosocial factors, with an emphasis on the mitochondrion."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180824/

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

From where I stand, it looks much like the equities market has given the sign of doom over the past couple of months. The view of the next couple of years I subscribe to is that equities will fall dramatically some more very soon, then there will be a variety of massive government intervention timed to influence the presidential elections in 2012. The markets will then rise much as they did after the last massive intervention, but fail to regain the highs of this year, and thereafter fall into the pit through 2013. All of these equity market gyrations, like those of the past couple of years, are just a symptom of the deep underlying economic malaise in what was formerly a grand economic powerhouse - though malaise is probably the wrong word, as it suggests something that just happened, faultlessly. This is very much a state of affairs created through the actions of a comparatively small number of people in positions of power - evenly distributed between government and financial industries in a symbiotic state of regulatory capture - and then again by the actions of the rest of us in letting them do what they do, in failing to understand enough of economics to see cause and effect, and in failing to act to stop this process.

It's no great secret that the US is decaying; this is history unfolding as a procedural. The US is ever more rapidly becoming just another Europe, Japan, or pick your dysfunctional fascist-leaning (per the dictionary definition) economy of choice. The ending of empires that centralize economic and legislative power, develop a ruling class, grow their military, and debase their currency is pretty much written in stone - it's the details of the move from wealth enjoyed in freedom to authoritarian poverty that will surprise people in their nature and timing.

But in any case, what does the sign of doom in the markets mean for the next few years of research funding, and especially speculative research funding for efforts such as SENS? In my experience it means much the same as it does for raising funds to launch startup companies. This is to say that when the economy is in the doldrums, raising funds is very challenging - especially when the equity markets have just started on their way down in earnest and fear is rife. Funding agencies and investors pull back, either because they've suffered losses or because they have the luxury of waiting for a few years for better times.

To my eyes that makes the next few years the time to double down on raising funds from high net worth philanthropists. These are people who will be slowing their normal flow of deals and investment, but who have most likely not suddenly lost wealth in any meaningful way. There is an argument to be made that investments in early stage research made in the shadow of a falling market and economic destruction will be more effective on a dollar for dollar basis: there may be greater access to researchers and resources at lower prices due to a downturn in the normal state of their employment, for example.

One rather important item to take away from all this is that, like everyone else, I'm wrong about the market at least half the time. The fundamentals underlying modern national economies, and the US in particular, are truly terrible, however. If markets are up, it's because they're being propped up by the Federal Reserve, most recently by an uncharacteristically direct process that amounts to devaluation of the dollar and pumping newly created-from-nothing money into equities. I consider these large-scale manipulations to be something that cannot continue forever: the only goals they achieve are (a) political, keeping one faction or another in favor by providing the modern equivalent of bread and circuses in the form of high equities prices, and (b) personal in the sense that some of the ruling class become very wealthy in the course of carrying out these activities. They don't create wealth in any meaningful sense, only the hollow illusion of it. Eventually the cards must come crashing down and the hole will grow too large to be filled in by the standard model of government bailout. As they say, the trouble with other people's money is that you eventually run out of it.

So maybe the next few years will see the US equities indexes much lower than they are now, and the fundraising scene a desert. Maybe not, but I think it more likely than the alternatives. If you're in the business of raising funds, now is the time to be stacking away for the coming winter, and finalizing all the deals you can.

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

A recent open access paper from a Spanish research group outlines yet another methodology to add to the growing list of ways to increase healthy life span in mice. Progress is signified by diversity these days; there are, I think, more than twenty different demonstrated methods of bringing about meaningful extension of life in mice as of today.

RasGrf1 deficiency delays aging in mice:

We observed that mice deficient for RasGrf1-/- display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals.

Aged RasGrf1-/- displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1-/-. IGF-I levels were lower in RasGrf1-/- than in controls. Furthermore, SIRT1 expression was increased in RasGrf1-/- animals. Consistent with this, the blood metabolomic profiles of RasGrf1-deficient mice resembled those observed in calorie-restricted animals.

...

Our observations link Ras signaling to lifespan and suggest that RasGrf1 is an evolutionary conserved gene which could be targeted for the development of therapies to delay age-related processes.

The results are similar to those noted for PAPP-A knockout mice - both longer lives and less cancer. At this stage it's anyone's guess as to whether many of these methodologies in fact operate through the same thicket of connections and mechanisms in mammalian biochemistry. Time, and further research, will tell.

RasGrf1 was mentioned here last year in connection with the intriguing bi-maternal mice:

mice artificially produced with two sets of female genomes have an increased average lifespan of 28%. Moreover, these animals exhibit a smaller body size, a trait also observed in several other long-lived mouse models. One hypothesis is that alterations in the expression of paternally methylated imprinted genes are responsible for the life-extension of bi-maternal mice. Considering the similarities in postnatal growth retardation between mice with mutations in the Rasgrf1 imprinted gene and bi-maternal mice, Rasgrf1 is the most likely culprit for the low body weight and extended lifespan of bi-maternal mice.

This latest work adds weight to the supposition quoted above.

Somewhere in the world, someone today pushed out the boundaries of what can be done with stem cells in medicine. The field is now so large and well funded that noteworthy advances are rolling in every week, and for each incremental step forward that you read about in the popular science press there are another half a dozen more behind the scenes, achieved without much commentary outside the scientific community. This is what a healthy field of research and development looks like: a lot of movement, a great deal of progress. Here are pointers to a few recent items, representative of what is taking place day in and day out around the world:

New Transplant Method May Eliminate Need for Lifelong Medication

The study found that a combination of two drugs lengthened survival time and prevented liver rejection in rodents. One drug was a low dose of tacrolimus, which prevented immediate rejection of the transplant, and the other was plerifaxor, which freed the recipient's stem cells from the bone marrow. The bone marrow cells freed by plerifaxor then traveled to the damaged liver and repopulated it with the recipients' own cells, replacing the donor cells that cause rejection. The stem cells also appeared to control immune response by increasing the amount of regulatory T-cells. Essentially, the scientists said they transformed the donor liver from a foreign object under attack by the immune system into an organ tolerated by the body within three months of the surgery. And - the rats only had to take the medications for one week after the transplant.

100-fold increase in efficiency in reprogramming human cells to induced stem cells

Researchers from the Wellcome Trust Sanger Institute have today announced a new technique to reprogramme human cells, such as skin cells, into stem cells. Their process increases the efficiency of cell reprogramming by one hundred-fold and generates cells of a higher quality at a faster rate. Until now cells have been reprogrammed using four specific regulatory proteins. By adding two further regulatory factors [retinoic acid receptor gamma (RAR-?) and liver receptor homolog (Lrh-1)], Liu and co-workers brought about a dramatic improvement in the efficiency of reprogramming and the robustness of stem cell development. The new streamlined process produces cells that can grow more easily.

Regenerating eyes using cells from hair

Limbal stem cell deficiency (LSCD) [is] a condition which causes the cornea to become cloudy and develop a rough surface causing pain and leading to blindness. Currently, treatments focus on harvesting limbal cells from a patient's healthy eye or from cadaveric tissue. In her pioneering research, Dr. Meyer-Blazejewska considered the potential use of stem cells harvested from hair follicles to reconstruct damaged tissue for patients who suffer from LSCD in both eyes. ... Dr. Meyer-Blazejewska's team demonstrated that in the right microenvironment stem cells from hair follicles do have the capacity for cellular differentiation, the process whereby a less specialized cell becomes a more specialized cell type, in this case the cells of the corneal epithelial phenotype. The team's results showed an 80% rate of differentiation in mouse eyes following a cell transplant highlighting the promising therapeutic potential of these cells.

Stem-Cell Clinical Trials Move Debate Beyond Labs

Next year, Pfizer Inc. and a clutch of British scientists hope to join a small but growing group of researchers conducting the first clinical trials in one of the more contentious areas of science: medical treatments derived from human embryonic stem cells. Pfizer and its partners at University College London's Institute of Ophthalmology are awaiting regulatory permission to begin a human study in the U.K. of a possible treatment for age-related macular degeneration, a common disorder in the elderly that can cause blindness.

The constant hum of progress from the field of stem cell science and development is what we'd like to see emerging from work on aging and longevity science - and needless to say we don't. There are not enough researchers, and there is not enough funding, and there is not enough popular support to build this sort of pace of progress at the present time. That is what we must strive to change.

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

Drinking coffee may reduce a person's chances of developing oral cancer and even brain tumors.

According to a study published in the medical journal Cancer Epidemiology, Biomarkers & Prevention, it was found that people who drank three to four cups of coffee per day reduced their risk of neck & head cancer by as much as thirty-nine percent.

According to Dr. Mia Hashibe, a researcher from the University of Utah, the findings of the new study is significant because coffee is one of the most popular beverages in the world.

The survival percentage for oral cancer and other associated cancers is low, so the findings provide hope for both men and women.  Unfortunately, the study did not make use of data from people who drank decaffeinated coffee.  In addition to oral cancer and neck cancer, another study (this time, from London)  discovered that coffee also reduced the risk of people developing tumors in the brain.

Other studies agree on the benefits of coffee

Studies around the world seem to acquiesce with the recent findings in the United States; it also appears that coffee may be more than just a cancer preventive:

1. A recent study performed in Sweden states that women who drank four to five cups of Scandinavian coffee (which requires boiling) reduced their risk of developing breast cancer over the long term.

It appears that boiled coffee provides more health benefits because it can contain up to eighty different fatty acids, which have been shown to have cancer-preventing effects when taken by the human body.  The benefits of boiled Scandinavian coffee was noted for women between the ages of 49 and 55.

2. According to researchers who published a study in the Journal of Agriculture and Food Chemistry, regular coffee intake may ward off adult-onset diabetes or type 2 diabetes.  In animal tests, it was shown that coffee increased the sensitivity of the animals to insulin.  Coffee was also effective in combating the sudden rise of blood glucose levels according to the researchers.

3. Past US studies show that coffee may be helpful in reducing LDL or “bad” cholesterol levels.  Coffee also contains polyphenols, which are natural antioxidants that protect the body from free radical damage.  Polyphenols are also present in abundant quantities in green tea.

4. Based on a Harvard Medical School study on aggressive/advanced prostate cancer and coffee-drinking, it was found that males who regularly drank coffee were sixty percent less likely to develop advanced prostate cancer, compared to males who did not drink coffee at all.

5. A Netherlands study produced the following findings for coffee consumption: 2 to 4 cups of coffee a day reduced the incidence of heart problems by twenty percent.  Coffee intake also slightly reduced the chances of a person dying from the most common causes (cancer, heart problems, stroke, heart attack, diabetes, etc.)

Sources:
sciencedaily.com
sciencedaily.com
sciencedaily.com
sciencedaily.com
sciencedaily.com
sciencedaily.com

Discuss this post in Frank Mangano’s forum!

Moderately skilled and experienced operators can make money by creating and maintaining a website on a particular topic. The degree to which money can be made by doing this is, at the highest level, a function of the level of interest in that topic - complicated by how much money flows in associated industries, but in general it is a measure of public interest and engagement.

Out there in the very fluid ecosystem comprised of small-scale entrepreneurs, online advertising networks, and the browsing population, you'll find an ever-changing and adapting group of websites associated with almost any topic that you find interesting. You have the basement level of automated spam blogs and tiny content sites, bottom feeders produced with minimal effort to generate a tiny amount of revenue each - but there are millions of them. Above that there are the institutional versions of those automated spam systems: companies that churn out terrible, banal content according to metrics that measure present interest in particular topics. Above that, the mix of old and young online journalism that does much the same thing, only more slowly and with a more idiosyncratic flavor.

Then you have the entrepreneurs who build and sell websites over the course of years in much the same way that some people buy, renovate, and sell houses. There is a well-established formula: you work on good (or rather good enough) content, pull in an audience, demonstrate worth, and then sell to another player in that marketplace. None of this implies that the entrepreneur has any interest whatsoever in the topic covered by the website - it helps if they do, but it isn't necessary.

This ecosystem, coupled with the vast sums of money that flow through the "anti-aging" marketplace, explains why 99% of the material out there on the topic of human longevity is junk, nonsense, machine-generated, or only present in the hopes that you'll click on a high-value ad. It is worthless garbage, produced by people who have no interest whatsoever in actually attaining the goal of longer lives through medical science. Over the past few years it seems the search engines have largely given up, their indexes clogged with useless pages created by ignorant outsiders for gain that push down the relevance of useful pages created by knowledgeable insiders.

This state of affairs is been a plague upon our houses, a blanket of lies and misdirection that has long made it extremely hard for newcomers to find any sane starting point in learning about longevity science. Discussion of fundraising and serious research can't get a word in edgeways around the jabbering of supplement-pushers and machine-generated sales pitches for the "anti-aging" products of magical thinking.

I mention all of this as I've noticed a slight shift in the strategy of the site-building entrepreneurs over the past year or so. I should mention that it is often the case that it is hard to tell the difference between one of their sites and a spam system, and their modus operandi in matters of aging and longevity has typically been to follow on the coattails of the "anti-aging" marketplace to push whatever expensive, unproven, and ultimately useless supplement is all the rage. Even sites run by people who are genuinely interested in radical life extension have largely made money through supplements - as that, so far as I can see, is the only game in town.

This becomes at some point a self-fulfilling prophecy: the vast majority of the ecosystem spews forth discussion of supplements and "anti-aging" nonsense - and so this is what the community hears, expects, and looks for. The for-profit websites are just as much a tool for education and advocacy as this site is, and sad to say they are generally far more effective at propagating the message they eventually settle on.

But of late, I've been seeing more site-building that incorporates the messages of rejuvenation biotechnology and modern, serious longevity science. Pulling in quotes from well known aging researchers, for example, talking about the Strategies for Engineered Negligible Senescence, and cutting back on the supplement-pushing. I'm not sure where the various entrepreneurs are going with this, but it seems to be a sign that the right sort of message is further spreading thanks to the efforts of advocates in the healthy life extension community. It is, after all, hard to talk up a $20 pitch while selling a $1 technology that looks pretty weak beside the ongoing work that the scientist next door is busy explaining.

Here are a couple of sites I've noticed of late - see if you can decipher the longer-term motivations of the builders. In each case, these are small-scale commercial ventures at various stages of their inception and progress; and I provide no assurances that any of the content you'll find is true, straightforward, or anything other than a hook aimed at your wallet.

Ageless Zoom

For most of my adult life I've had the sense that I was to participate in bringing in the future. But I never clearly knew what that meant. Now we are able, if we choose, to live longer than any life-span humans have ever imagined. That's not mere possibility, it's real and at hand. I think of it as a second lifetime. And for me it's a very real opportunity to move from chance to choice.

Extreme Longevity

Extreme Longevity is an Internet publication dedicated to finding and presenting the latest developments in human longevity research. ... Each day thousands of scientists and researchers around the world are working to gain a greater understanding of what processes make living things age and seek to determine methods to slow down, stop, or even reverse this process. ... At Extreme Longevity you can expect the latest research to be presented regularly in concise easy-to-understand articles which emphasisze how best to put these learnings in to practice.

Immortal Humans

The latest news and developments about humankind's drive towards biological immortality.

That last one is a good example of a site that can be hard to tell apart from a spam blog - but the entrepreneur responsible for it emerged to comment back a ways when I first noted its existence.

There are others I could point out, but a representative set of three is more than enough. Take them for what they are, and ponder what their existence indicates in terms of the present strength and propagation of the message on scientific longevity.

From ShrinkWrapped: "If a physical change affects half of all people as they age, this would seem to suggest that it is a normal variant of human aging, which to the best of our knowledge is an accumulation of metabolic and genetic errors that accrue as we get older until some sub-unit(s) of the processes reach a threshold at which continued functioning of the body is impossible. Our current regulatory apparatus remains trapped in a 20th century mindset which fails to recognize how various diseases are nothing more than unfortunate variants of the aging process that all of us will one day fall prey to. For example, in Alzheimer's 'Disease' errors of metabolism (malformed proteins) in neurons in the brain lead to an accumulation of defective protein parts which eventually disrupt the functioning of the neuron, ultimately killing it. When this process has gone on long enough to have damaged and destroyed some as yet unknown fraction of the brain, the person becomes neurologically symptomatic. This 'Disease' is not communicable, nor is it caused by an exogenous agent. The damage to the brain occurs as the result of biological failure that all of us will have to face in one form or another. ... The FDA does not recognize aging as a treatable condition and only approves treatment for 'Disease.' ... Because the FDA only evaluates treatments for Diseases, and its definition of disease versus aging is completely arbitrary (why is Type II Diabetes a disease while Sarcopenia, the loss of muscle mass and function that accompanies aging, is not?) we are forced to develop treatments that primarily address symptoms rather than either repairing damage or rejuvenating systems."

View the Article Under Discussion: http://shrinkwrapped.blogs.com/blog/2010/07/when-is-a-disease-not-a-disease.html

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

An open access anthropology paper on cryonics, illustrating in a number of subtle and less subtle ways the eternal divide between students of soft sciences and students of hard sciences: "Cryonics is a particularly American social practice, created and taken up by a particular type of American: primarily a small faction of white, male, atheist, Libertarian, middle- and upper-middle-income, computer/engineering 'geeks' who believe passionately in the free market and its ability to support technological progress. In this article, I investigate the relations between the discourses and practices of cryonics and its underpinnings in the values associated with neoliberal capitalism. I take seriously the premise that cryonics is an investment in the possibility of an extended future and a potential insurance policy against death. I show how cryonics is conceived of as an attempt to gain sovereignty over the limits of biological time, achieved through both monetary investment and the banking of biological objects understood to be actual selves. Cryonics demonstrates a unique way in which time, capital, and biotechnoscience can come together in the name of future life. An examination of the extreme example of cryonics reveals how speculative economic reasoning is applied to lives and bodies in the United States. I argue that cryonics is one response to American anxieties about time, the impending decline of the human body, and its culmination in death that draws on logics of biomedicine, technological progress, and investment forms. I describe some of the many unique aspects of cryonics and some of its similarities to venture capitalism, mainstream biomedical practice, and other sites where investment in the self and biotechnoscience come together, chiefly in other forms of tissue banking."

View the Article Under Discussion: http://www.informaworld.com/smpp/section?content=a921989939&fulltext=713240928

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

From the MIT Technology Review: "Rats genetically engineered to lose their sight can be protected from blindness by injections of human neural stem cells ... a startup in Palo Alto, CA, plans to use the positive results to file for approval from the U.S. Food and Drug Administration to begin human trials. The company is already testing the cells in children with a rare, fatal brain disorder called Batten's disease. ... The company's cells are isolated from human fetal tissue and then grown in culture. To determine whether these cells can protect against retinal degeneration, scientists studied rats that were genetically engineered to progressively lose their photoreceptors - cells in the retina that convert light into neural signals. These animals are commonly used to model macular degeneration and retinitis pigmentosa, two major causes of blindness that result from cell loss in the retina. Researchers injected about 100,000 cells into the animals' eyes when the rats were 21 days old. ... the cells migrate over time, forming a layer between the photoreceptors and a layer of tissue called the retinal pigment epithelium, cells which nourish and support the photoreceptors. ... the cells protected vision in the part of the retina in which they were implanted."

View the Article Under Discussion: http://www.technologyreview.com/biomedicine/25647/?a=f

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

Via EurekAlert!: "For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease. ... It is generally accepted that the buildup of artery-blocking plaque stems from the body's immune response to vessel damage caused by low-density lipoproteins ... Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue ... The scar tissue, known as neointima, has certain characteristics of smooth muscle, the dominant type of tissue in the blood vessel wall. Because mature smooth muscle cells no longer multiply and grow, it was theorized that in the course of the inflammatory response, they revert, or de-differentiate, into an earlier state where they can proliferate ... However, no experiments published have directly demonstrated this de-differentiation process ... researchers turned to transgenic mice with a gene that caused their mature smooth muscle cells to glow green under a microscope. In analyzing the cells from cross sections of the blood vessels, they found that more than 90 percent of the cells in the blood vessels were mature smooth muscle cells. They then isolated and cultured the cells taken from the middle layer of the mouse blood vessels. ... Notably, none of the new, proliferating cells glowed green, which meant that their lineage could not be traced back to the mature smooth muscle cells originally isolated from the blood vessels. ... We did further tests and detected proteins and transcriptional factors that are only found in stem cells. No one knew that these cells existed in the blood vessel walls because no one looked for them before. ... In the later stages of vascular disease, the soft vessels become hardened and more brittle. Previously, there was controversy about how soft tissue would become hard. The ability of stem cells to form bone or cartilage could explain this calcification of the blood vessels. ... Other tests in the study showed that the multipotent stem cells were dormant under normal physiological conditions. When the blood vessel walls were damaged, the stem cells rather than the mature smooth muscle cells became activated and started to multiply." Though if you want to consider root causes, look at mechanisms like accumulated damage to mitochondria that leads to a greater level of oxidized low-density lipoproteins in the blood.

Link: http://www.eurekalert.org/pub_releases/2012-06/uoc--trc053112.php

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

From Maria Konovalenko: "I met Dr. Bredesen during the Buck Advisory Council meeting at the Buck Institute for Research on Aging in Novato, California on May 21. [The] Advisory Council consists of influential individuals who can contribute to Buck Institute's mission of advancing aging research. A very interesting crowd. ... Dale Bredesen opened the mini conference with his report on Alzheimer's research. The majority of scientists envision this horrible degenerative process as accumulation of toxic molecules, namely amyloid beta and tau proteins. Amyloid beta forms plaques between the cells and tau protein tangles inside the cells. These toxic proteins disrupt the functions of our neurons. ... So, Dr. Bredesen views Alzheimer's disease differently - as an imbalance between synaptic maintenance and synaptic reorganization. The thing is that for our brain to function properly we need to form connections between our neurons, and also we need to break down those connections that we no longer need. According to Dale Bredesen, this balance disrupts, it shifts towards synaptic reorganization, we loose our memory, face the horrors of loosing our consciousness and eventually we die. ... So how can we preserve this balance? Dr. Bredesen's lab studies the underlying mechanisms of neurodegeneration. There were able to find out that one of the things that contributes to the balance shift is the change in APP cleavage. APP is amyloid precursor protein. It is concentrated in synapses of our neurons. APP can break down into either two, or four parts. When it breaks down into 2 parts those proteins are sAPP alfa and CTF alfa. This is a 'good' combination. However, during aging amyloid precursor protein cleavage shifts towards the 'bad' combination, which is sAPP beta, Amyloid beta, Jcasp and C31. This is the shift in balance that leads to the onset of disease. The shift can be restored. The mouse strain that has one mutation that leads to not having APP to break down to Jcasp and C31 proteins leads to restoring memory in mice. But the most exciting thing is that Dr. Bredesen is testing a drug that shifts the APP cleavage balance back to normal."

Link: http://mariakonovalenko.wordpress.com/2012/07/03/dale-bredesen-alzheimers-is-a-problem-of-imbalance-not-toxicity/

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

It is unfortunate that popular culture, that ongoing conversation of countless threads that lies at the center of our diverse society, is so focused on drugs and pills as the sum of all medicine - anything that is consumed, and so especially when it comes to influencing the pace of aging. It is a terribly wrong, horribly damaging viewpoint, but one that is relentless propagated by the loudest voices, coincidentally also those who gain the most in the short term by creating a culture of customers for their products. When the world thinks of medicine for aging in terms of pills and potions, it shuts the door on support for real rejuvenation biotechnology, such as the detailed plans for development advocated by the SENS Foundation and others.

Part of the process of building the true medicine of rejuvenation - which will look like gene therapies, tailored cell alterations, engineered enzymes to strip away harmful metabolic side-products, and so on - is obtaining the support and at least superficial understanding of the public at large. That is still very much lacking, and some fraction of the blame for that can be pinned on the short-sighted idiots of the "anti-aging" marketplace who propagate lies and myths about aging and what can be done about it in order to sell products that do next to nothing. They have spent so much time and effort on this over the past decades that they have shaped the visions of popular culture to follow their message - and that harms us all by stripping away possible support for meaningful research and development, and making it harder to create that support.

The vast majority of commentary on aging, science, longevity, and what can be done about it is garbage at worst, and interesting but ultimately irrelevant to the future of our lives at best. Into the latter half falls work on calorie restriction mimetics such as metformin and rapamycin. They simply don't do enough to worth sinking billions of dollars into further research and development - though of course that research and development will happen anyway, regardless of my opinions on the matter. There are far better paths ahead than tinkering with compounds and genes that have modest effects, on a par with calorie restriction, and potentially serious side-effects to go along with that.

If results are what matter - and I think they are the only measure worth considering given the pace of death caused by aging - then world of aging and longevity research should focus on the SENS vision of targeted, deliberate repair of specific forms of damage, and move on from the tired old model of patching the end results of damage by trying a lot of compounds to find some that sort of do something beneficial. Nor should research spend their time on the comparatively new approach of trying to slow down the pace at which damage accumulates - again by trying a bunch of compounds to find some that sort of do something beneficial.

There are now far more effective paths forward for the treatment of aging than the approaches undertaken in past decades when biotechnology and the state of knowledge was too poor to do better. The world of aging science must up-end, change, become quite different. The SENS Foundation and the network of research groups working on related matters are doing the right thing. Big Pharma, the calorie restriction mimetic developers, the people searching for longevity genes or gene therapies to slow aging - they are heading down a side-path that will do little beyond generating new knowledge. Our lives will not be greatly lengthened by their efforts, as we will be old by the time that they produce therapies with modest effects on human life span by slowing down the pace at which damage accumulates. Ways to slow aging are of little value to those already aged. Our healthy lives will be significantly extended only by the successful development of methods of rejuvenation - of damage repair, ways to actually reverse the toll of aging on cells and systems.

Which, conveniently, are planned out and proposed in some detail.

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

You might recall research published a couple of months ago on calorie restriction and heart function. It illustrated (again) that people who practice calorie restriction over the long term have physiologically younger cardiovascular systems - meaning notably less low-level cellular damage and better function than their peers of a similar chronological age.

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. [Researchers] 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.

If there was a drug that did that, its financials would be staggering - and you'd never hear the end of it. It would be publicized and popularized in every corner of the world. But just ask someone to exercise a little willpower and planning in their diet to gain the same results ... and therein lies a lesson with regard to human nature.

I notice that the institutional publicity machine at Washington University in St.Louis has caught up with this research; if you'd like a little more commentary from the researchers involved, that's the place to look:

"This is really striking because in studying changes in heart rate variability, we are looking at a measurement that tells us a lot about the way the autonomic nervous system affects the heart," says Luigi Fontana, MD, PhD, the study's senior author. "And that system is involved not only in heart function, but in digestion, breathing rate and many other involuntary actions. We would hypothesize that better heart rate variability may be a sign that all these other functions are working better, too."

...

"Higher heart rate variability means the heart can adjust to changing needs more readily," says lead author Phyllis K. Stein, PhD. "Heart rate variability declines with age as our cardiovascular systems become less flexible, and poor heart rate variability is associated with a higher risk of cardiovascular death."

...

"The idea was to learn, first of all, whether humans on CR, like the calorie-restricted animals that have been studied, have a similar adaptation in heart rate variability," Fontana says. "The answer is yes. We also looked at normal levels of heart rate variability among people at different ages, and we found that those who practice CR have hearts that look and function like they are years younger."

...

"In many of our studies, we have found that a number of metabolic and physiologic changes that occur in calorie-restricted animals also occur in people who practice CR," Fontana says. And he says the finding that heart rate variability is better in people who practice CR means more than just that their cardiovascular systems are flexible. He says the better ratio suggests improved health in general.

"But we can't be absolutely positive that the practice of CR is solely responsible for the flexibility of the cardiovascular system," Stein says. "People who practice CR tend to be very healthy in other areas of life, too, so I'm pretty sure they don't say to themselves, 'Okay, I'll restrict my calorie intake to lengthen my life, but I'm still going to smoke two packs a day.' These people are very motivated, and they tend to engage in a large number of very healthy behaviors."

The point on calorie restriction practitioners practicing good health across the board is a fair one - peeling apart the beneficial effects of regular exercise from the beneficial effects of calorie restriction in humans, for example, is an interesting challenge. Still, it would be hard, I think, to find a population of humans who are exceptionally health-conscious without practicing calorie restriction and who nonetheless exhibit a youthful physiology to the degree seen in calorie restricted people. There are different classes of mechanism at work here.

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

One of the costs of being sedentary is fiscal: the cost of medical services you would otherwise not have needed due to your increased risk of age-related disease. Here is another researcher running the numbers: "Physical inactivity is a recognized public health issue in Canada and globally ... A common approach for assessing the public health impact of physical inactivity is to measure the prevalence of the population not meeting physical activity guidelines. Recent surveillance data based on objective measures indicate that 85% of Canadian adults do not meet Canada's physical activity guidelines of 150 min/week of moderate-to-vigorous physical activity ... A second approach for assessing the public health impact of physical inactivity is to estimate the proportion of a disease within the population that is directly attributable to physical inactivity. For instance, 19% of the coronary artery disease cases in Canadian men are due to physical inactivity ... A third approach for assessing the public health impact of physical inactivity is to estimate the financial burden it places on the health care system and economy. The most recent Canadian estimates, based on 2001 data, suggest that the annual economic burden of physical inactivity is $5.3 billion. ... Similar to the 2001 estimates, the health care cost of physical inactivity in this report was estimated using a prevalence-based approach, which required 3 pieces of information: (1) the risks of chronic conditions in physically inactive individuals, (2) the direct and indirect costs of these chronic diseases, and (3) the prevalence of physical inactivity in the population. ... The estimated direct, indirect, and total health care costs of physical inactivity in Canada in 2009 were $2.4 billion, $4.3 billion, and $6.8 billion, respectively. These values represented 3.8%, 3.6%, and 3.7% of the overall health care costs." It is interesting to compare these numbers with research on individual lifetime medical cost differences that stem from being out of shape, and with some other number crunching on the economics of health and longevity.

Link: http://www.nrcresearchpress.com/doi/full/10.1139/h2012-061

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

Researchers have demonstrated modest progress towards the goal of making the body's existing cell populations rebuild damaged cartilage in situ:

A small molecule dubbed kartogenin encourages stem cells to take on the characteristics of cells that make cartilage, a new study shows. And treatment with kartogenin allowed many mice with arthritis-like cartilage damage in a knee to regain the ability to use the joint without pain. ... The new approach taps into mesenchymal stem cells, which naturally reside in cartilage and give rise to cells that make connective tissue. These include chondrocytes, the only cells in the body that manufacture cartilage.

...

"In the blue-sky scenario, this would be a locally delivered therapy that would target stem cells already there," says study coauthor Kristen Johnson, a molecular biologist at the Genomics Institute of the Novartis Research Foundation in San Diego. Johnson and her colleagues screened 22,000 compounds in cartilage and found that one, kartogenin, induced stem cells to take on the characteristics of chondrocytes. The molecule turned on genes that make cartilage components called aggrecan and collagen II. Tests of mice with cartilage damage similar to osteoarthritis showed that kartogenin injections lowered levels of a protein called cartilage oligomeric matrix protein. People with osteoarthritis have an excess of the protein, which is considered a marker of disease severity. Kartogenin also enabled mice with knee injuries to regain weight-bearing capacity on the joint within 42 days.

As a long term goal for tissue engineering, controlling existing cell populations sufficiently well to rebuild lost or damaged structures in the body is preferable to strategies that involve surgery - such as, for example, building cartilage outside the body and then implanting it. Both avenues are under development at this time.

One consequence of an increased focus on controlling stem cells in the body is that researchers must find ways to reverse the stem cell decline that comes with aging. If stem cell populations are generally less effective, then therapies based on directing those cells may be of limited benefit. Given that most of the regenerative therapies we can envisage will be of greatest use to the elderly, the people who bear the most damage and bodily dysfunction, and who are generally the wealthiest portion of the population, there is a strong financial incentive to find ways to build working therapies for that market. This is why I see the regenerative medicine community blending in at the edges with the longevity science community in the years to come - many of the goals are much the same.

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

The response of metabolism to lowered methionine intake appears to be a major component of the mechanisms of calorie restriction: "Methionine dietary restriction (MetR), like dietary restriction (DR), increases rodent maximum longevity. However, the mechanism responsible for the retardation of aging with MetR is still not entirely known. As DR decreases oxidative damage and mitochondrial free radical production, it is plausible to hypothesize that a decrease in oxidative stress is the mechanism for longevity extension with MetR. In the present investigation male Wistar rats were subjected to isocaloric 40% MetR during 7 weeks. It was found that 40% MetR decreases heart mitochondrial ROS production at complex I during forward electron flow, lowers oxidative damage to mitochondrial DNA and proteins, and decreases the degree of methylation of genomic DNA. ... These results indicate that methionine can be the dietary factor responsible for the decrease in mitochondrial ROS generation and oxidative stress, and likely for part of the increase in longevity, that takes place during DR. They also highlight some of the mechanisms involved in the generation of these beneficial effects."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22006472

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