Senescent cells build up in our tissues with age. They have left the cell cycle, damaged and dysfunctional, fail to self-destruct through one of the many systems for cell suicide, and linger on to cause all sorts of problems for their neighbors. Tissue riddled with senescent cells is less effective, less resilient, and more prone to developing further damage.

One of the roles of the immune system is to clear out these problem cells, but the immune system itself progressively fails in all its tasks with age, a victim of its own issues. So the senescent cell population grows, promoted by increasing levels of damage caused by the other processes of aging, and the immune system fails to rein it in.

Here, researchers demonstrate one specific result of an increased population of senescent cells: an additional susceptibility to lung infection over and above the issues caused by an age-damaged immune system.

The researchers found that when it comes to aging and pneumonia, one bad apple can ruin the barrel. Lung cells that were supposed to die due to DNA damage - but didn't - were 5 to 15 times more susceptible to invasion by pneumonia-causing bacteria. These bad apples also increased the susceptibility of normal cells around them.

Both age and [pneumonia] are associated with senescent cells, which are unable to die due to dysregulated function. These cells have increased levels of proteins that disease-causing bacteria stick to and co-opt to invade the bloodstream. The cells also spew out molecules that increase inflammation, and make normal cells nearby do the same.

How will we deal with senescent cells with near future biotechnology? The likely answer is through the use of technologies pioneered in cancer research: precision cell-killing strategies that can locate and destroy very specific types of cell without harming any other cell types. These may use nanoparticles or they may involve training the immune system to attack senescent cells with vigor, but both paths have been demonstrated effective in the laboratory.

Sadly, as for so much of what might be done, next to no-one is actually working on adapting these developing technologies for use against senescent cells. That's one more thing to add to the long term to-do list for Open Cures and a strategy of promoting overseas development of new biotechnologies.

Transdifferentiation is the act of changing a cell directly from one type to another, without having to first go through the process of producing induced pluripotent stem cells and then differentiating them into the desired final product. This shows some promise as a yet more effective way of producing cells to order for research and therapies: "Human skin cells can be converted directly into functional neurons in a period of four to five weeks with the addition of just four proteins ... The finding is significant because it bypasses the need to first create induced pluripotent stem cells, and may make it much easier to generate patient- or disease-specific neurons for study in a laboratory dish. It may also circumvent a recently reported potential problem with iPS cells, in which laboratory mice rejected genetically identical iPS cells - seemingly on the basis of the proteins used to render them pluripotent. The new research parallels that of the same Stanford group in 2010, which showed it was possible to change mouse skin cells directly into neurons with a similar combination of proteins. However, when done in human cells, the conversion of skin cells to neurons occurs less efficiently and more slowly. ... We are now much closer to being able to mimic brain or neurological diseases in the laboratory. We may perhaps even be able to one day use these cells for human therapies. ... The direct conversion of skin cells to neurons contrasts with similar research that first transforms skin cells to a pluripotent, or developmentally flexible, state and then coaxes them to become neurons or other specialized cells. ... The iPS cell approach is doable and has been shown to work. We need to keep working on both strategies. It's possible that the best approach may vary depending on the disease or the type of research being done."

Link: http://www.eurekalert.org/pub_releases/2011-05/sumc-ss052511.php

This open access work looks like a solid way to measure accumulated biochemical damage in nematode worms, and link it to both its causes and its resulting effects on life span: "A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates. To unveil mechanisms that influence aging variability, we identified markers of remaining lifespan for Caenorhabditis elegans. In transgenic lines, we expressed fluorescent reporter constructs from promoters of C. elegans genes whose expression change with age. The expression levels of aging markers in individual worms from a young synchronous population correlated with their remaining lifespan. We identified eight aging markers, with the superoxide dismutase gene sod-3 expression being the best single predictor of remaining lifespan. Correlation with remaining lifespan became stronger if expression from two aging markers was monitored simultaneously, accounting for up to 49% of the variation in individual lifespan. ... Our results indicate that pathogenicity from Escherichia coli used as food is a major source of lifespan variability due to variable activation of the insulin-signaling pathway. ... E. coli, the common diet for worms, is mildly pathogenic whereas Bacillus subtilis is not pathogenic. Accordingly, worms fed B. subtilis live longer than worms grown on E. coli. ... The finding that the amount of sod-3 expression present in a middle-aged worm is correlated with its remaining lifespan indicates that events have occurred that affect its future aging trajectory. If so, feeding a worm either E. coli or B. subtilis should have greatest effect when it is young rather than when it is old. To test this, we fed worms one type of bacteria (E. coli or B. subtilis) when they were young and then shifted them to the other type of bacteria at day 8 of adulthood. Young worms fed E. coli had short lifespans, no matter what they ate when they were old. Conversely, young worms fed B. subtilis had long lifespans no matter what they ate when they were old. This result indicates that pathogenicity or some other factor associated with E. coli initiates changes in young worms that affect their time of death later on."

Link: http://dx.doi.org/10.1371/journal.pgen.1002047

There are three parallel tracks along which the future development of longevity science must progress, and we'll reach the end goal only as rapidly as the slowest of the three tracks moves.

1) Science and Biotechnology

The most obvious of the tracks is that the technologies of rejuvenation must be developed. We can see what the form that these technologies must take: damage repaired, waning cell populations renewed, waste byproducts broken down and removed, cancer thwarted. Initiatives like SENS can describe the needed procedures in great detail, at the level of cells and molecular machinery, as we truly are within a tantalizingly close reach of their creation.

But the biotechnologies of rejuvenation don't yet exist, and the many technology demonstrations of long-lived mice, flies, and worms in laboratories around the world are nothing but a warm-up for the main event. Even the amazing pace of progress in stem cell medicine and cancer research these days is just a toe across the starting line when it comes to true rejuvenation. A great deal of work lies ahead, for all that it is very clear just what that work must be.

We are truly fortunate in comparison to the previous generation of activists and scientists in being able to state the nature of a cure for aging. We can see exactly what it is that we need to accomplish - and so our job should be that much easier than theirs in many ways.

2) Clinical Development

Taking the output of the scientific method and turning it into reliable, affordable, widely available technology is no less a challenge than scientific progress. It is fraught with risk, and the stakes are much higher: the cost of developing new science is small in comparison to the costs of building an industry. Moving from one technology demonstration and a few patients to a technology used by hundreds of thousands of patients around the world is a massive undertaken in risk, development, innovation, and cutthroat competition.

Today, we see the impersonal engines of bureaucracy engaged in crushing this track to the future of longevity science. Practical medicine lags far behind practical science, and the costs of pushing through each new development program increase every year - thanks to organizations like the FDA, whose appointees have no incentive to do anything other than make it ever harder to bring new biotechnologies to the marketplace. In the case of longevity science, matters are yet worse than in other fields, as the FDA outright forbids commercial development of therapies for aging.

That the track of development and clinical translation of research is lagging so badly is what prompted me to the vision of the Vegas Group. That in turn led to the recent launch of Open Cures - an initiative to help speed commercial development of longevity science. There are plausible, cost-effective ways in which matters can be put right, making use of the existing institutions of medical tourism, overseas research and development, the internet, and the growing community of garage biotech and open biotech developers.

3) Persuasion

People strongly enough in favor of engineered human longevity to get up and do something about it, who have a fair layman's or better grasp of the science, and thus know enough to support research like SENS rather than fall for any of the nonsense put out by the "anti-aging" industry, probably number a few thousand. There are probably tens of thousands more of a similar mindset, but not are motivated enough to contribute materially beyond conversation and hope.

You can change the world with ten thousand people who think the same way as you do, that much is true, but it will be hard and it will take a long, long time. In the end, you'll only succeed by convincing hundreds of thousands more to contribute their support. It does't require all the world to agree with you. Half a percentage point of the world's population is hundreds of millions of people. Markets with hundreds of millions of customers are worth billions of dollars, even though they gain only a tiny, tiny fraction of the attention and expenditure of those people - and billions of dollars would be more than enough to fund the first emergence of true rejuvenation biotechnology.

The form of the track that lies ahead for advocacy is well known: at the highest level, all grand campaigns of persuasion are the same, and there are many successful examples to choose from in the field of patient advocacy. But it is a long way from where we are, a core group of thousands, to where we want to be - a core group of millions. Much remains to be accomplished.

An open access paper in which researchers delve into the mechanisms of longevity induced through calorie restriction in yeast: "Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. ... . Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan. ... CR-induced NO production may extend lifespan by increasing the stress response (mitohormesis). Our study may have uncovered potential novel components in the CR pathway and provided tools to analyze the interconnections between NO, mitochondrial respiration, CR, and longevity. Although the CR mimics identified in this study share similar NO levels, lifespan, and oxygen consumption phenotypes with CR, they may activate NO production and regulate mitochondrial respiration and lifespan via different mechanisms. It will be enlightening to examine these differences in future studies. Finally, we propose that CR likely confers its beneficial effects via a mitochondria-NO-mediated adaptive metabolic shift, which optimizes metabolism and at the same time improves cellular defense system against the oxidative stress that accumulates with age."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092605/

I'd missed the emergence of the latest issue of Rejuvenation Research last month, which opens with this:

Possibly the biggest battle that I have had to fight over the past decade is to persuade people to take seriously the idea that it is time even to think about "reversing aging" while we remain so negligibly able even to slow aging down. The flaw in that logic is simple: it is that rejuvenation, i.e. the restoration of an organism's physiological state to how it was at an earlier age, will be achieved not by reversing the processes of aging but by repairing the accumulated damage that those processes create. To get back to where we came from, in other words, we do not need to retrace the route we took from there to here. Any route will do, and in this case there turns out to be a vastly more plausible route than the retracing one.

The debate over the the large-scale course of longevity science, focusing on either repair of aging (thus effectively reversing its effects) or slowing aging through re-engineering human metabolism, will determine how long we all live.

It is likely to be easier and less costly to produce rejuvenation therapies than to produce a reliable and significant slowing of aging. A rejuvenation therapy doesn't require a whole new metabolism to be engineered, tested, and understood - it requires that we revert clearly identified changes to return to a metabolic model that we know works, as it's used by a few billion young people already. Those rejuvenation therapies will be far more effective than slowing aging in terms of additional years gained, since you can keep coming back to use them again and again. They will also help the aged, who are not helped at all by a therapy that merely slows aging.

Whatever the course of research, the first resulting widespread therapies to significantly extend healthy human life are two or more decades away. Most of us will be old before the second generation of better and more reliable therapies emerges thereafter. Thus repair strategies for ongoing research must come to dominate the funding landscape over the next decade if we are to see meaningful progress in engineered human longevity within our lifetimes. Slowing aging will be of little use to us by the time it becomes available.

All of this means that this scientific debate is far too important for all of us to refrain from participation. We should all absolutely dive in and loudly offer our own opinions on the topic, and help the researchers and fundraisers focused on repair biotechnologies succeed in their aims: it is, after all, the future of all our lives on the line.

A novel view of the mechanisms of neurodegeneration: "o one knows the cause of most cases of Alzheimer's, Parkinson's and other neurodegenerative disorders. But researchers have found that certain factors are consistently associated with these debilitating conditions. One is DNA damage by reactive oxygen species, highly destructive molecules usually formed as a byproduct of cellular respiration. Another is the presence of excessive levels of copper and iron in regions of the brain associated with the particular disorder. ... A high level of copper or iron, they say, can function as a 'double whammy' in the brain by both helping generate large numbers of the DNA-attacking reactive oxygen species and interfering with the machinery of DNA repair that prevents the deleterious consequences of genome damage. ... We don't yet know enough about all the biochemical mechanisms involved, but we have found multiple toxic mechanisms linking elevated iron and copper levels in the brain and extensive DNA damage - pathological features associated with most neurodegenerative disorders. ... some people's tissues contain much larger quantities of iron or copper, which overwhelm the proteins that normally bind the metals and sequester them for safe storage. The result: so-called 'free' iron or copper ions, circulating in the blood and able to initiate chemical reactions that produce reactive oxygen species. Reactive oxygen species cause the majority of the brain cell DNA damage that we see in Alzheimer's and Parkinson's disease, as well as most other neurodegenerative disorders."

Link: http://www.eurekalert.org/pub_releases/2011-05/uotm-hic052011.php

As a sign of changing attitudes amongst run of the mill journalists whose first reaction is to mock everything that isn't widespread knowledge, this is encouraging: "Want to live to be a thousand years old? It's not far-fetched at all if you ask theoretician and geneticist Aubrey de Grey. He believes within the next 25 years there is a 50/50 chance we'll have the technologies to extend human life indefinitely. I learned of Aubrey and his ideas in 2005 and immediately pitched the story to NBC's Today Show. They were intrigued. With the help of correspondent Kerry Sanders and the London bureau, we went out and interviewed Aubrey in a pub in Cambridge. When we finished the story we sent it in to the show. It was promptly killed. Too out there for a mainstream audience. Plus it didn't help that Aubrey looked like Methuselah. Fast forward to 2011 and there Aubrey was in the news again. This time I pitched the story to HDNet's World Report. The program is always looking for stories that deal with interesting issues and are not widely told. This time correspondent Willem Marx met up with Aubrey in a pub in Cambridge and also went punting with him on the Thames River. For my part, I finally got to meet Aubrey at his SENS Foundation laboratory in Mountain View, California. He is tall and wiry and moves like someone with no time to lose. He lovingly strokes the beard which hangs almost to his waist. I asked him if his distinctive look helped or hurt him as he went out in the world trying to win over scientists and venture capitalists to support his work. He said it helped because people looked at him and saw a guy who is not materialistic in the least. It's very clear to them that he is not doing this to get rich. Through his SENS Foundation nonprofit, Aubrey and the scientists who work with him are creating an intersection between research on the biology of aging and regenerative medicine. By doing experiments with the building blocks of cells they hope to someday develop treatments that repair the damage caused by aging, and restore people to a state where they are biologically younger than they were when they started. In other words, people could live out their entire lives as healthy as young adults. Five years ago, the scientific community considered his ideas kind of kooky but now the research is catching up with his theories and Aubrey is gaining credibility. 'This is not science fiction anymore, this is science forseeable,' Aubrey proclaims."

Link: http://www.huffingtonpost.com/vicky-collins/longevity-research_b_858244.html

Vitamin E has been shown to improve liver function for those with fatty liver disease. This is a serious issue that impacts approximately 5% of Americans and can actually be fatal in some cases.

One of the most common liver diseases related to obesity is called fatty liver disease.  Unfortunately, doctors currently believe that this issue has no form of treatment.  However, researchers from the Virginia Commonwealth University have discovered that Vitamin E can help patients with fatty liver disease.  Researchers were surprised at these findings, as typically vitamin supplements are only thought by medical professionals to treat problems caused by nutritional deficiencies.

When people have fatty liver disease, fat can build up in the liver and cause inflammation as well as scarring.  Eventually this can cause a liver to fail in some extreme cases.  Fatty liver disease is common in middle-aged people who are overweight.  Up to 5% of Americans are reported to have this issue.

In this new study, 247 people with advanced fatty liver disease were assigned to one of three groups.  One group took vitamin E in a high dosage, one group took a placebo and one took a diabetes drug called Actos. Biopsies showed that those who took Vitamin E saw a 43% increase in liver function.  While participants who took Actos also saw improvement in their livers, the percentage of increased liver function was not as high as in the group taking Vitamin E.  Also these people who took Actos gained weight during the experiment.

Other treatments for fatty liver disease include losing weight by eating right and exercising.

Aside from treating fatty liver disease, Vitamin E also has a number of other health applications.  As an antioxidant, it can fight cell damage that is caused by free radicals.  It can also protect against prostate cancer and Alzheimer’s disease.  As Vitamin E taken in large doses can be toxic, be sure to follow the recommendation on the label.  Also, consult with your physician prior to supplementing with Vitamin E if you’re taking a blood thinner.

Last but not least, synthetic vitamin E doesn’t work the same as natural Vitamin E.  Therefore, be sure to take the natural form, which is D-alpha tocopherol.

Sources:
news.yahoo.com
whfoods.com

Discuss this post in Frank Mangano’s forum!

Following up on recently published research into changes in body temperature brought about by the practice of calorie restriction in humans, I see that a release from a few days ago contains some interesting remarks from the researcher:

Individuals who significantly reduce their calorie intake have lower core body temperatures compared to those who eat more. The new finding matches research in animals. Mice and rats consuming fewer calories also have lower core body temperatures, and those animals live significantly longer than littermates eating a standard diet. ... What is interesting about that is endurance athletes, who are the same age and are equally lean, don't have similar reductions in body temperature.

...

What we don't know is whether there is a cause/effect relationship or whether this is just an association. But in animal studies, it's been consistently true that those with lower core body temperatures live longer. ... in an unrelated study called the Baltimore Longitudinal Study of Aging, scientists found that men who had lower core body temperatures, probably for genetic reasons, lived significantly longer than men with higher body temperatures. So it appears body temperature may predict longevity in humans, too.

...

For now, animal models suggest that simply lowering body temperature isn't enough to increase lifespan. In mice and rats that regularly swam in cold water, core body temperature dropped due to exposure to the cold water. But those animals didn't live any longer than normal rodents. Fontana says it appears that how lower temperatures are achieved is important. "I don't think it ever will be possible to be overweight and smoking and drinking and then take a pill, or several pills, to lower body temperature and lengthen lifespan," he says. "What may be possible, however, is to do mild calorie restriction, to eat a very good diet, get mild exercise and then take a drug of some kind that could provide benefits similar to those seen in severe calorie restriction."

Calorie restriction is chiefly interesting for its beneficial effects on health and longevity - which are nothing short of stunning in comparison to any presently available medical technology. It's the best present option for immediately and rapidly improving the health of basically healthy people. The evidence for it and the effects in studied human populations are so good that - if you are essentially healthy, in good shape, and would like to stay that way for as long as possible - you'd really have to have be digging for excuses not to be practicing calorie restriction.

All that said, calorie restriction is only slowing aging - and if we want to do better, to avoid becoming frail and aging to death, the only viable path forward is biotechnology along the lines of the Strategies for Engineered Negligible Senescence. If repair technologies for our biology are not developed soon enough, then all we gain through calorie restriction is a healthy life, probably a little longer, almost certainly with a lower cost of medical treatment and fewer chronic diseases of aging. To do better than that, to regain the vigor and health of youth and obtain extra decades of life, we need to support and encourage rapid advances in medical technology.

Someone who didn't take note of the eagerness with which people throw money at the shams, fakes, and security blankets of the "anti-aging" marketplace might be forced to conclude that the world's inhabitants are on balance indifferent as to whether they live long or die young, whether they suffer for decades or live healthily some years down the line. There are many common sense health practices that people can undertake to maximize their remaining life expectancy and reduce the risk of age-related disease - and that's even before we start in on supporting research and development of rejuvenation biotechnology - but the majority don't do anywhere near as much as they might, and in consequence they come to suffer for it.

Are we a species whose dominant trait is actually nihilism? One wonders at times.

But the personal future of aging isn't the only thing that most people, judging by their actions, are indifferent to. We might also consider the preventable nature of well known conditions like cancer, to pick one example. Most people know that they should be exercising, they should not let themselves get fat, and they also know how to halve the risk of suffering cancer - but do they adopt the necessary changes in lifestyle? Largely no:

More than half of all cancer is preventable, and society has the knowledge to act on this information today ... What we know [is] that lifestyle choices people make and that society can influence in a number of ways - from tobacco use to diet and exercise - play a significant role in causing cancer. Specifically, the researchers cite data demonstrating that smoking alone is responsible for a third of all cancer cases in the United States. Excess body weight and obesity account for another 20 percent.

This all might be viewed as another facet of the difficulty faced by groups trying to do something about aging and age-related disease - which is to say trying to help people avoid a future that many to most seem to be largely indifferent to, judging by their actions. If a person doesn't care enough about their future trajectory to take basic, simple care of their health today, why would they care enough to donate money to medical research and development? Fortunately, it isn't necessary to persuade everyone - even a few tens of millions of casual supporters, a tiny fraction of the population of the world, could between them generate enough resources to carry the SENS research program to completion, for example. Cancer research is itself an example of what it looks like some decades after that initial group of casual supporter is amassed - once the ball starts rolling and achieves a critical mass, the research programs become accepted as a part of what is.

But we are still left wonder on the rationality of humans, and the degree to which the average person is prepared to let their future self suffer.

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

From TechNewsWorld: "During his homily this Easter, Pope Benedict argued that medical science, in trying to defeat death, is leading humanity toward likely condemnation. It's a position at odds with the value of life, one that the Church will likely revise years from now, replaying the institution's embarrassment over censoring Galileo. ... If scientists are successful in finding techniques to rebuild cartilage, repair organs, and cure cancer, people will indeed be living longer - but they will also be healthier, more energetic and youthful. Health-extension, when it happens, will allow people to live longer, better. Consider that 60-year-olds today are not in the same shape as their counterparts were in the 1800s or 1900s. As humans discovered how to take better care of themselves, through improved nutrition, the use of antibiotics and other techniques, 'chronological age' became less synonymous with 'biological age.' That is, many of today's 60-year-olds act and feel much younger than one might expect. The average human life expectancy today is close to 80 years but in 1850, it was 43 years, and in 1900 it was 48 years. One can imagine someone in 1850 arguing that doubling life expectancy would be terrible, because innovation might be at risk and there would be more old people around. But would anyone today say they are sorry that science made it possible to live longer and healthier lives?"

View the Article Under Discussion: http://www.technewsworld.com/story/Galileo-20-Here-Comes-Another-Apology-69876.html

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

This EurekAlert! release looks at some of the challenges facing the increasing number of research groups who are attempting to destroy cancer stem cells: "Many of the colon cancer cells that form tumors can be killed by genetically short-circuiting the cells' ability to absorb a key nutrient, a new study has found. While the findings are encouraging, the test tube study using human colon cancer cells also illustrates the difficulty of defeating these cells, known as cancer stem cells (CSCs). ... It is becoming more evident that only a small number of cells in the tumor are capable of forming the tumor, namely the cancer stem cell. So the new strategy is to eliminate the cancer stem cells and thus lower the recurrence of cancer. ... Because CSCs have properties similar to normal stem cells, we have to find a way to attack them while keeping the adult stem cells alive. ... To do that, the research team inactivated a receptor that is found in increased amounts in colon cancer cells: the insulin-like growth factor receptor (IGF-1R). The colon cancer CSCs seem to need a fair amount of IGF to live, more than other cells, and they can't function without the IGF receptor. ... Working with human colon cancer cells, the researchers manipulated the cellular genetics using small interfering RNA (siRNA) to prevent the synthesis of IGF-1R. In this way, they reduced the number of IGF receptors by half, and reduced the number of CSCs by 35%."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-04/foas-ras042210.php

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

An example of the how advances in biotechnology are allowing medicine to move closer towards intervening in first causes at the biochemical level: researchers "have developed a new approach for identifying the 'self' proteins targeted in autoimmune diseases such as multiple sclerosis, diabetes and rheumatoid arthritis. ... errant immune responses which mistakenly target the body's own proteins rather than foreign invaders can now be examined in molecular detail. Further research could lead to new insights into the exact causes of these debilitating autoimmune disorders. ... The immune system, the body's main line of defense against disease, has a critical responsibility to distinguish self-derived proteins from those of invaders like viruses and bacteria. Autoimmune diseases arise when a person's immune system fails to make that critical distinction and mistakenly attacks a normal tissue, such as nerve, joint, or insulin-producing pancreatic cells. ... Knowledge of the self-antigens involved in autoimmune processes is important not only for understanding disease etiology, but also for developing diagnostic tests. In addition, physicians may someday use antigen-specific therapies to destroy or disable auto-reactive immune cells. ... But looking through the haystack of cellular complexity for those single-needle self-antigens targeted by the immune system has proved daunting, to say the least. Ideally, scientists would be to develop some kind of biological magnet that could pull these fine needles out of the mass. In this report, the researchers describe an approach which does just that."

Link: http://www.eurekalert.org/pub_releases/2011-06/hms-apn060211.php

There is plenty of evidence to show that being overweight for any great length of time in life causes harm, either fairly directly by boosting levels of chronic inflammation, or because that fat tissue is associated with a lack of exercise and consequent development of vascular dementia, or for a range of other possible reasons. Here is another study on this topic: "High midlife body mass index (BMI) has been linked to a greater risk of dementia in late life, but few have studied the effect of BMI across midlife on cognitive abilities and cognitive change in a dementia-free sample. ... We investigated the association between BMI, measured twice across midlife (mean age 40 and 61 years, respectively), and cognitive change in four domains across two decades in the Swedish Adoption/Twin Study of Aging. ... Latent growth curve models fitted to data from 657 non-demented participants showed that persons who were overweight/obese in early midlife had significantly lower cognitive performance across domains in late life and significantly steeper decline in perceptual speed, adjusting for cardio-metabolic factors. Both underweight and overweight/obesity in late midlife were associated with lower cognitive abilities in late life. However, the association between underweight and low cognitive abilities did not remain significant when weight decline between early and late midlife was controlled for. ... There is a negative effect on cognitive abilities later in life related to being overweight/obese across midlife. Moreover, weight decline across midlife rather than low weight in late midlife per se was associated with low cognitive abilities." The weight decline association shows up in a range of studies on weight and health; one common conclusion is that it reflects the impact that more serious medical conditions - related to weight or otherwise - can have on people.

Link: http://www.ncbi.nlm.nih.gov/pubmed/22450854

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

An interesting discovery: "Reprogramming of somatic cells to a pluripotent state was first accomplished using retroviral vectors for transient expression of pluripotency-associated transcription factors. This seminal work was followed by numerous studies reporting alternative (non-insertional) reprogramming methods, and various conditions to improve the efficiency of reprogramming. These studies have contributed little to an understanding of global mechanisms underlying reprogramming efficiency. Here we report that inhibition of the mTOR (mammalian target of rapamycin) pathway by rapamycin or PP242 enhances the efficiency of reprogramming to induced pluripotent stem cells (iPSCs). Inhibition of the insulin/IGF-1 signaling pathway, which like mTOR is involved in control of longevity, also enhances reprogramming efficiency. In addition the small molecules used to inhibit these pathways also significantly improved longevity in Drosophila melanogaster. We further tested the potential effects of six other longevity-promoting compounds on iPSC induction, including two sirtuin activators (resveratrol and fisetin), an autophagy inducer (spermidine), a PI3K (phosphoinositide 3-kinase) inhibitor (LY294002), an antioxidant (curcumin) and an AMPK (activating adenosine monophosphate-activated protein kinase) activator (metformin). With the exception of metformin, all of these chemicals promoted somatic cell reprogramming, though to different extents. Our results show that the controllers of somatic cell reprogramming and organismal lifespan share some common regulatory pathways, which suggests a new approach for studying aging and longevity on the basis of the regulation of cellular reprogramming."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21615676

From the SENS Foundation: "For Max, working at the [SENS Foundation Research Center (SENSF-RC)] has been the culmination of years of dedicated study and preparation. Before he first heard about SENS in early 2005, he wasn't a scientist at all; in fact, he was a 23-year-old cost accountant. When he wasn't studying for his MBA, he was counting other people's money. He knew that he wanted more out of life, though: specifically, he wanted to change the world in a way that would benefit society. As soon as he found and read Aubrey de Grey's Ending Aging, he settled on human health as the area he would strive to impact - and on SENS as the way to make that impact. Over the next few years he committed himself to working in finance, at one point teaching at a local community college, always with the intention of saving his money so that he could return to school to learn about science and laboratory work. During this period he studied whenever he had the time, reading articles relevant to health and aging in scientific journals. In 2008, Max went back to school full-time at the University of Toledo to study chemistry, math, and biology. He was interested in taking an active role in SENS research as quickly as he could, so he contacted the predecessor of the SENS Foundation Academic Initiative, MFURI. As a member of the Initiative, he performed a literature review on the harm caused by iron and aluminum accumulation in the body, citing well over a hundred journal articles. Max's paper was accepted by the journal Rejuvenation Research and published in April 2010, just as he was completing his coursework at Toledo. As his next step, Max opted to join the RC staff rather than pursue a PhD opportunity so that he could continue to make as direct and immediate of a contribution to SENS as possible. Max has now been working at the SENSF-RC for one year, and will be staying on to continue his work on the A2E degradation project. In the long term, he hopes to see the LysoSENS project through all of its pre-clinical stages. It is his wish that this work will lead to therapies that can effectively reverse, or at the least greatly slow, the pathology of age-related macular degeneration."

Link: http://www.sens.org/node/2036

Aging research is the poor cousin of the life science field, despite the fact that the overwhelming majority of the harm brought to humanity through disease, frailty, and death is basically caused by aging. Work on extending life or reversing aging is in turn the poor cousin in the aging research family. This situation must change for the better if we are to see meaningful progress in our lifetimes.

A recent article puts some numbers to the picture, here for the Buck Institute, which is one of the largest mainstream laboratories specializing in aging research.

In this fiscal year, the institute will receive about $23 million in government grants, about 66 percent of its $35 million budget. The institute will also get about $5.6 million from the Marin Community Foundation - down from close to $8 million before the economic downturn - and about $5 million from individual and corporate donations.

Compare that with the SENS Foundation, which is currently running a with a yearly budget of a little over $1 million, and is completely reliant on philanthropic donations.

These are small numbers when considered against the broader field of medical research and development. They reflect a society that has not yet woken up to decide that repair of aging is in fact both a possibility and a priority. The feedback loop of education from scientists to the public and support from the public to scientists isn't yet running well for longevity science - it is running better than it was a decade ago, but clearly there is much work to be done.

A review paper: "Aging is a gradual process during which molecular and cellular processes deteriorate progressively, often leading to such pathological conditions as vascular and metabolic disorders and cognitive decline. Although the mechanisms of aging are not yet fully understood, inflammation, oxidative damage, mitochondrial dysfunction, functional alterations in specific neuronal circuits and a restricted degree of apoptosis are involved. Physical exercise improves the efficiency of the capillary system and increases the oxygen supply to the brain, thus enhancing metabolic activity and oxygen intake in neurons, and increases neurotrophin levels and resistance to stress. Regular exercise and an active lifestyle during adulthood have been associated with reduced risk and protective effects for mild cognitive impairment and Alzheimer's disease. Similarly, studies in animal models show that physical activity has positive physiological and cognitive effects that correlate with changes in transcriptional profiles. According to numerous studies, epigenetic events that include changes in DNA methylation patterns, histone modification and alterations in microRNA profiles seem to be a signature of aging. Hence, insight into the epigenetic mechanisms involved in the aging process and their modulation through lifestyle interventions such as physical exercise might open new avenues for the development of preventive and therapeutic strategies to treat aging-related diseases."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21624506

Hormesis is the process by which a little damage or stress to our biology can lead to a longer life span, as it wakes up the repair mechanisms and makes them do a better job than they otherwise would - a net gain in resiliency. Here is a review that summarizes the implications for much of mainstream research into aging and longevity: "Various nutritional, behavioral, and pharmacological interventions have been previously shown to extend life span in diverse model organisms, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mice, and rats, as well as possibly monkeys and humans. This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote increased formation of reactive oxygen species (ROS). These serve as molecular signals to exert downstream effects to ultimately induce endogenous defense mechanisms culminating in increased stress resistance and longevity, an adaptive response more specifically named mitochondrial hormesis or mitohormesis. Consistently, we here summarize findings that antioxidant supplements that prevent these ROS signals interfere with the health-promoting and life-span-extending capabilities of calorie restriction and physical exercise. Taken together and consistent with ample published evidence, the findings summarized here question Harman's Free Radical Theory of Aging and rather suggest that ROS act as essential signaling molecules to promote metabolic health and longevity." ROS can of course be acting both as useful signals and sources of damage in different circumstances - the fact that life can be extended by antioxidants specifically targeted to mitochondria, coupled with the evidence mentioned above, suggests that much.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21619928