Singularity Hub looks at the tissue engineering of teeth: "For years, researchers have investigated stem cells in an effort to grow teeth made for a person's own cells. Toward this end, [scientists] have developed methods to control adult stem cell growth toward generating dental tissue and 'real' replacement teeth. [The] researchers' approach is to extract stem cells from oral tissue, such as inside a tooth itself, or from bone marrow. After being harvested, the cells are mounted to a polymer scaffold in the shape of the desired tooth. The polymer is the same material used in bioreabsorable sutures, so the scaffold eventually dissolves away. Teeth can be grown separately then inserted into a patient's mouth or the stem cells can be grown within the mouth reaching a full-sized tooth within a few months. So far, teeth have been regenerated in mice and monkeys, and clinical trials with humans are underway, but whether the technology can generate teeth that are nourished by the blood and have full sensations remains to be seen. Teeth present a unique challenge for researchers because the stem cells must be stimulated to grow the right balance of hard tissue, dentin and enamel, while producing the correct size and shape."

Link: http://singularityhub.com/2012/05/10/toothless-no-more-researchers-using-stem-cells-to-grow-new-teeth/

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

Extreme Longevity notes an Italian study: "Sardinia [is] especially rich in male centenarians. The present study was undertaken to quantify and determine which particular lifestyle and nutritional variables endemic to Sardinia males accounted for their extreme longevity. The authors point out that no genetic differences have been found between Sardinian males and less long-lived males found elsewhere in Italy so they reasoned lifestyle choices were more likely causative of their longevity than genetic factors. The researchers specifically compared the frequency of several dietary choices and lifestyle factors between men of Sardinia and Italian men not from Sardinia. It was particularly surprising that diet alone didn't account for the differences. The frequency of meat, cheese, wine, grain and nut consumption was identical in the two groups. Total daily caloric intake was slightly but insignificantly lower in the Sardinian men. The most significant difference found was in the distance to work and average slope of the terrain between the men of Sardinia and those from other regions. The researchers conclude it is likely the large amount of daily physical exercise required to walk long distances up steep mountain climbs that has led to the increased longevity of Sardinian males. They point out the effect of physical exercise on extending longevity is becoming widely recognized, appearing at the conclusion of many scientific articles."

Link: http://extremelongevity.net/2011/10/04/vigorous-daily-exercise-linked-to-extreme-male-longevity/

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

It is the common wisdom that retirement from active work speeds the process of decline - and there are all sorts of reasonable explanations as to why this might be the case, but insofar as actual supporting evidence goes you're not going to find much of a consensus. That said, here is an unusual paper amongst those in search of a correlation between retirement and a shorter remaining life span: "Mortality hazard and length of time until death are widely used as health outcome measures and are themselves of fundamental demographic interest. Considerable research has asked whether labor force retirement reduces subsequent health and its mortality measures. Previous studies have reported positive, negative, and null effects of retirement on subsequent longevity and mortality hazard, but inconsistent findings are difficult to resolve because (1) nearly all data confound retirement with unemployment of older workers, and often, (2) endogeneity bias is rarely addressed analytically. To avoid these problems, albeit at loss of generalizability to the entire labor force, I examine data from an exceptional subgroup that is of interest in its own right: U.S. Supreme Court justices of 1801-2006. Using discrete-time event history methods, I estimate retirement effects on mortality hazard and years-left-alive. ... Estimates by all these methods are consistent with the hypothesis that, on average, retirement decreases health, as indicated by elevated mortality hazard and diminished years-left-alive. These findings may apply to other occupational groups characterized by high levels of work autonomy, job satisfaction, and financial security."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21948108

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

Via ScienceDaily: "Glioblastoma is one of the most aggressive forms of brain cancer. Rather than presenting as a well-defined tumor, glioblastoma will often infiltrate the surrounding brain tissue, making it extremely difficult to treat surgically or with chemotherapy or radiation. ... [scientists] developed a method to combine a tumor-homing peptide, a cell-killing peptide, and a nanoparticle that both enhances tumor cell death and allows the researchers to image the tumors. When used to treat mice with glioblastoma, this new nanosystem eradicated most tumors in one model and significantly delayed tumor development in another. ... This is a unique nanosystem for two reasons. First, linking the cell-killing peptide to nanoparticles made it possible for us to deliver it specifically to tumors, virtually eliminating the killer peptide's toxicity to normal tissues. Second, ordinarily researchers and clinicians are happy if they are able to deliver more drugs to a tumor than to normal tissues. We not only accomplished that, but were able to design our nanoparticles to deliver the killer peptide right where it acts - the mitochondria, the cell's energy-generating center. ... In this study, our patients were mice that developed glioblastomas with the same characteristics as observed in humans with the disease. We treated them systemically with the nanoparticles. Once the nanoparticles reached the tumors' blood vessels, they delivered their payload (a drug) directly to the cell's power producer, the mitochondria. By destroying the blood vessels and also some surrounding tumor cells, we were able to cure some mice and extend the lifespan of the rest,"

Link: http://www.sciencedaily.com/releases/2011/10/111003151828.htm

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

Researchers continue to explore what stem cells might be able to achieve for the regeneration of serious injuries: "adult human mesenchymal stem cells may have an important role in the treatment and repair of spinal cord injuries. Mesenchymal stem cells (MSCs) are found mainly in the bone marrow and are the focus of many clinical trials that investigate potential methods of neurological repair and other regenerative applications. ...Although mesenchymal stem cells are widely known to be used in replacing damaged tissue, these stem cells may also recruit endogenous cells (those made within the body) to help accelerate the repair process. ... For the first time, [researchers] examined the use of human MSCs to prompt repair of spinal cord injuries in transgenic (genetically engineered or altered) zebrafish embryos. Zebrafish are especially valuable to researchers due to invertebrate characteristics that are similar to those of humans, the transparency of their bodies and their ability to initiate regeneration of damaged tissue. The study demonstrates that human MSCs affix to the injury site and influence spinal cord cells to accelerate the repair process. ... Our results indicate that MSC therapy not only augments recovery after spinal cord injury, but also accelerates the recovery time"

Link: http://www.newswise.com/articles/research-indicates-that-adult-human-mesenchymal-stem-cells-may-be-viable-treatment-for-spinal-cord-injury-repair

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

As I might have remarked upon back in the Fight Aging! archives, there is something about the idea of greatly extending human life through medical technology that sends otherwise sane people off the deep end. Mention the topic and you'll hear screeds on class warfare, relinquishment of progress in medicine, death before inequality, and visions of immortal tyrants lording it over mortal serfs. Nonsense, the lot of it, all utterly divorced from the history that shows us time and again exactly how change, even radical change, progresses in a technological society - but people say this stuff anyway.

there are a great many unrealistic viewpoints in the world that would hinder or halt longevity research, either directly or indirectly. Viewpoints like "the more regulation the better", "prove that you will do no harm at all before we'll let you move forward," or "let us redistribute all property and remove incentives for success and progress, for inequality for any is worse than death for all" spring to mind. In this latter context, "social justice" is a particularly pernicious phrase, being a shorthand for forceful redistribution of wealth by government fiat - institutionalized theft, aimed exactly at the point at which it will do the greatest damage to progress by removing incentives for success.

The world works this way: we can labor and trade to move everyone ahead, benefits for all and inequalities for all, or we can redistribute what presently exists - which at best leads to stagnation and no progress, and at worst becomes a repetition of Soviet era Russia and Eastern Europe. In both cases, inequality will be there - you can't kill it. The choice is whether it's inequality in comparative wealth or inequality in poverty, disease and rubble. Progress is absolutely dependent on freedom and the incentives of wealth earned through hard work and invention.

People react to the prospect of rejuvenation biotechnology in ways that are completely different from their reactions to, say, the highly effective next generation of cancer therapies. You don't hear people declaring that late stage treatments for cancer will split the world into warring factions of haves and have nots, or that all development must be halted until it can be offered to everyone. If you walk through all the varied nonsense spouted on the topic of society and radical life extension, and replace rejuvenation with stem cell heart therapies, or cures for cancer, or organs such as blood vessels grown to order - then you might start to see just how nutty it sounds. Medical technologies just as revolutionary have emerged in the past, and will continue to do so without being horded, restricted to the rich, tearing the world asunder, turning brother against brother, and causing cats to lie with dogs.

But aging and longevity has a lot of baggage, it seems. So I see that Sonia Arrison, blogging on radial life extension at the Volokh Conspiracy, took some time early on to address the standard nonsense on class warfare and social justice style "equality":

Could class conflict or even warfare break out over life-extension technologies? It is true that technology is rarely adopted by everyone at the same time, and when life-extending science hits the market, it will almost certainly be used by the wealthy first. ... New technologies are almost always adopted by the rich first, but over time they eventually reach everyone, and the historical record shows that the distribution of new technology is speeding up, not slowing down. For instance, it took forty-six years for one-quarter of the population to get electricity and thirty-five years for the telephone to get that far. It took only sixteen years, however, for one-quarter of American households to get a personal computer, thirteen years for a cell phone, and seven years for Internet access. A more vital example may be AIDS drugs which started off costing about $30,000 per patient per year 15 years ago. Now, better drugs are available and cost $100 per patient. ... The fact that the first users of life-extending technologies will tend to be wealthy increases the chances that the technologies will thrive and eventually reach everybody. Without private investors who believe in the value of a new product and want to support its development, many great ideas would be stillborn. History bears this out, from Queen Elizabeth owning some of the first silk stockings, to wealthy New Yorkers paying $20 in 1915 for a three-minute phone call to San Francisco.

I've long thought it rather sad that so much of our society is bludgeoned into the chattering classes' view of everything laid out in terms of class, conflict, redistribution, forced organization in a top-down fashion, and all the other unfortunate ideals that come with strong centralization of power. Their viewpoints are completely divorced from any sensibility as to how progress actually occurs, or how wealth is in fact created. They are thus one of the first barbarians hammering at the gate: people ignorant of the causes of the success of their society, yet still wealthy enough to be somewhat shielded from the immediate consequences of such ignorance. It never lasts forever, of course: in the end this will come to the same sorry end as Rome or the British Empire, and the US will become a shell of what it once was, a population living amidst the ruins of past grandeur, so constrained by their government as to have forgotten how to achieve greatness and prosperity once again.

The only silver lining is that scientific knowledge is no longer lost alongside the roots of wealth and prosperity; the world has become too small for that, and knowledge will move to the places where it can be best preserved. So those glories, at least, will continue even when the research community that produced them can no longer be sustained.

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

Long-standing businesses must index everything they do to the changing - almost always falling - value of their regional currency, but very few smaller businesses do this in any sort of a deterministic way. Your average talented and determined fellow willing to start a company knows a lot about the business itself, but generally isn't very knowledgeable regarding currencies, inflation, finance, and so forth. That sort of expertise doesn't emerge in a company as a matter of course until it becomes much larger. So smaller businesses deal with the falling value of money by raising their prices as best they can on an ad hoc basis, but this is ever a challenge for products that involve very long memberships. Trying to raise rates on existing customers is, frankly, one of the hardest things a business can do. But raise rates they must, as modern paper currencies have long been set on a relentless spiral of devaluation.

This happens because politicians and government bureaucrats can use the strategic devaluation of their national fiat currency as a way to generate significantly more revenue for a given level of public upheaval than can be achieved through direct taxation - so of course they tend to do exactly that. This is why inflation exists, and is arguably why fiat currencies continue to enjoy such wide, legally-enforced use. So fiat currencies are somewhat systematically, somewhat opportunistically devalued over time in ways that result in a transfer of wealth from the public at large and into the control of politicians, bureaucrats, and their close supporters.

This is one of a number of processes that make long-term prognostication on future costs a challenge. Others include assumptions on the economies of scale that will emerge with success in development, or success in popularity of a product - successful products invariably become much cheaper as they become more widespread. This happens because competitors figure out more effective means of building the product, and because it is usually cheaper on a per-unit cost to build a hundred widgets rather than ten widgets.

The cryonics industry is presently running into a number of these issues. It offers products that are commonly paid for over decades, or where decades might elapse between the ink drying on a contract and the actual provision of service. The industry is decades old, but never grew to the point at which experience in managing the consequences of currency devaluation and other long-term strategic issues would naturally emerge amongst the major players in a field. At Alcor, this manifests as a growing underfunding issue, and to the credit of the present management they are openly publishing their current thinking on the matter:

The cryonics economies anticipated by Robert Ettinger in 1965 were never realized. By the 1970s, the cost of whole body cryopreservation as offered by TransTime and Soma (the for-profit arm of IABS, which later merged with Alcor) was $60,000. As shown in Fig. 1, the nominal dollar cost of cryonics has risen steadily with Consumer Price Index (CPI) inflation since then. By 2011, the minimum funding for whole body cryopreservation with Alcor was $200,000. Even this large number has not kept pace with inflation, so another increase will be necessary soon.

Whenever Alcor has increased cryopreservation minimums, it has traditionally only required new members to meet new minimum funding requirements. Existing members were "grandfathered," and allowed to remain members even if their cryopreservation funding fell below new minimums. This was and is believed to be important for members who due to age or disability become uninsurable, and would otherwise have to leave Alcor after many years of supporting the organization. ... However the main way that Alcor coped with grandfathering was by just taking the loss on what was historically a small number of underfunded cases. There was never a quantitative analysis of the impact of grandfathering, or a specific financial plan for dealing with it. ... The sustainability of this has been questioned on numerous occasions.

You should read the whole thing; it outlines the problem, puts numbers to it to show the size, and presents a range of possible solutions, along with discussion of their merits.

The bottom line is that businesses must act like businesses, even when they have their roots in the non-profit space, research, advocacy, and saving the world, as is the case for most of the ongoing cryonics concerns. There's no such thing as a free lunch, and the cost of providing a service has to be met somehow - if it isn't, then the whole product structure and relationship with the customer has to be rethought. The challenges of managing business agreements across decades have to be addressed by cryonics providers one way or another, such as by continually and clearly indexing against inflation for customers, or by using specialized financial instruments akin to futures contracts, as is the practice in many industries that have to make very long-term commitments and want to shield their customers from the complexity inherent in doing that.

In practice, things are always more complicated and intricate than the sweeping statements I give above, but I think an organization willing to put out a document that talks through their issues in this way is an organization with the right mindset to come to a solution. Openness is a virtue in this modern world, and I think that it is a very beneficial approach to customer relations when those relations have to extend across decades. Many of the most successful companies can be said to have communities as much as they have customers, and I don't see that as being a bad thing for the cryonics industry.

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

MItochondrial function, structure, and damage are clearly important to longevity, both within and between species, so it should be no surprise to find mitochondrial DNA haplogroups associated with variations in human longevity: "Human longevity is a complex heritable genetic trait. Based on substantial evidence from model organisms, it is clear that mitochondria play a pivotal role in aging and lifespan. However, the effects that mitochondrial genome variations have upon longevity and longevity-related phenotypes in Zhuang people in China have yet to be established. By genotyping 15 variants for 10 haplogroups in 738 Zhuang subjects, including 367 long-lived individuals and 371 controls, we found that haplogroup F was significantly associated with longevity in females of Zhuang population of China. Additionally, haplogroup F was related to higher HDL levels in long-lived individuals. Further analysis suggests that the non-synonymous variant m.13928G>C in haplogroup F was also associated with longevity in female Zhuang Chinese which might account for the beneficial effect of F."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21945877

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

Suffering from obesity and eating disorders has been linked to depression cases, a serious disorder that can worsen one’s health and prove to be fatal.

The latest report from Gallup-Healthways Well-Being Index shows an alarming figure—that almost one-fourth of obese American citizens have all been diagnosed with depression. What is surprising is not that these people at some point in their lives were depressed, because every person may be at risk of developing the disease; but that the reported percentage exceeds the percentage of people with normal weight, who have simultaneously been clinically-diagnosed with the said psychiatric disorder.

Furthermore, the new survey shows that one out of four adult Americans that are obese have higher chances of reporting that they experience various negative emotions — such as anxiety, stress, sadness, anger — compared to those whose weight is considered normal. Gallup also noted that having a little extra weight does not yield the same effects of obesity, considering that results showed how the overweight respondents experienced negative emotions in almost the same league as those with normal weight.

The participants who were part of the conducted surveys were classified based on their body mass index scores — as calculated through the participants’ own reports regarding their weight and heights.

• Obese people were those whose BMI scores start from 30 and more.
• Overweight people were those whose BMI scores ranged from 25.0-29.9.
• Respondents with normal weight were those who yielded BMI values from 18.5 to 24.9.
• Underweight participants were those who yielded BMI scores below 18.5.

Based on these classifications, Gallup claimed that 36.3 % of Americans are currently overweight whereas 26.7 % are reportedly suffering from obesity. Simultaneously, 35 % of adult Americans currently enjoy a healthy or normal weight.

Revealing Survey Results: The Notable Obesity Factor

The yielded findings were based on over 250,000 interviews that were conducted within 8 months—from January to September of 2010. The following provides a breakdown of the significant survey results:

• 23.2 % of adults, all of whom are plagued with obesity, report that they suffer from depression based on clinical diagnosed; whereas only 14.9% of overweight people, 14.3% of normal-weight individuals, and 19.1% of people who are deemed to be underweight reported that they been diagnosed.
• 41.6 % of the obese individuals are prone to feeling all stressed up; whereas 39.4% of those with normal weight, and 42% of those who are underweight reportedly feel the same.
• 34.5 % of obese individuals reported that they worry; whereas 30.6% of those with normal weight, and 35.9% of those who are underweight said that they also worry.
• 15.7% of the obese people reportedly experience anger; whereas 12.6% of those with normal weight and 16% of underweight individuals also feel anger.
• 19.9 % out of the group of obese individuals experience sadness; where as 16.3% of those with normal weight, and 21.3% of underweight individuals reported that experienced sadness.

Such results also show the possibility for clinically-diagnosed depressed people to have higher chances of suffering from obesity, stress, and worry.

Link between Being Underweight and Being Depressed

Gallup claims that underweight people account for 1.7 % of adult American citizens. According to an email by Dan Witters, Gallup’s scientist on well-being, to WebMD — many underweight individuals suffer from eating disorders. This incidence significantly explains why the survey results showed that a large percent of those who are underweight have also been diagnosed as depressives. For one, both eating disorders called bulimia and anorexia have strong links to depression, regardless of the victim’s gender; and anorexia appears to have a strong relationship with women’s suicide-related deaths. He further said that in women-related cases, depression strikes prior to eating disorder.

Healthy and Natural Weight Loss and Weight Maintenance

Given the strong links between depression and obesity, along with being underweight; it is important for people who suffer from obesity and eating disorders to start anew and commit to a healthy weight loss and maintance plan, through maintaining and losing weight for better overall health—physically, mentally, and emotionally.

Setting manageable and healthy long-term goals

Setting one’s goals is the first important step before embarking on any attempt at weight loss or weight maintenance. During this preparatory stage, it is important to note that the best way to lose and maintain weight is to do so without losing one’s health.

Anyone who wants to take on the task of losing weight in a healthy manner must look far ahead, instead of merely counting a couple of days and a few weeks and wanting to see immediate, drastic results. Having a long-term horizon goal for weight loss and maintenance targets three essentials— safe weight loss and maintenance, successful weight loss and maintenance, and lasting or sustainable weight loss and maintenance. The ideal weight loss and maintenance plan should include proper and regulated exercise, eating a balanced and healthy diet on a regular basis, using natural supplements, changing one’s attitudes towards exercise and eating, and applying lifestyle modificaitons that can be continuously sustained.

Exercise

This suggestion does not pose itself as an option — it is essential and mandatory for optimal success. Ideally, the exercise program must include aerobic exercise for burning calories, through interval training; and weight-bearing exercise for burning calories during sleep, as achieved through muscle-building.

The exercise needs not to be immediately laborious. Starting with an enjoyable stroll and a light jog can be good boosters in order to enhance one’s metabolism and energy. Soon, the person becomes more capable of lengthening his allotted time for exercise routines, and adding more activities. A full exercise program that lasts around 30 minutes, done at least three times a week, is more than enough for healthy results.

Healthy diet to naturally cause weight loss and maintenance

While one is at the process of losing weight, it is essential to never forget that he must be wary of what he eats. It has been too repetitive to speak of how consuming a variety of fresh fruits, fresh vegetables, foods rich in calcium, and foods with high concentrations of healthy fats such as omega-3 fatty acids are important in one’s daily diet. However, these suggestions are cliches that never go wrong. Such foods offer multi-benefits that not only aid a healthy and natural weight loss and weight maintenance program, but also help in reducing one’s risk of developing unwanted diseases. Normal weight and good health can be achieved, simultaneously.

Supplements will not work as a magic pull by themselves, but their name already suggests their integral role— to further assist successful and sustainable weight loss and maintenance. Healthy supplements include green coffee bean extract and oolong tea, mulungu, bacopa, herbs and several others.

Furthermore, paying attention to what one eats enables the person to automatically refrain from foods that must be avoided—such as highly aunnatural fatty dishes, foods rich in sugar, and processed foods.

Paying attention to eating behavior and attitudes

Eating slowly poses several benefits, primarily through helping keep up with the time needed before the brain acknowledges that the person ise= already full, which usually takes up to 15 minutes. Furthermore, eating a lot as an option to attain comfort in the midst of negative emotions, such as tiredness or depression, must be avoided: Efforts to battle these negative emotions can be  diverted to other activities. It is also important not to skip breakfast, and to ensure that it accounts for the largest meal intake in the day. This attitude will stop the person from feeling unnecessarily hungry, and will also enhance his energy levels as he faces the day.

Sources
webmd.com
cdc.gov
nhlbi.nih.gov
jonbarron.org
flat-stomach-exercises.com

Discuss this post in Frank Mangano’s forum!

There is clearly a point in Alzheimer's, and other neurodegenerative diseases, beyond which the damage caused by the condition is irreversible. Neurons die, and in large enough numbers to destroy vast swathes of information held in the brain - the very foundation of who you are, and the vital components of systems needed to live a normal life. All is not gloom, however. Studies in past years have suggested that up to that point, much of the loss of function that accompanies Alzheimers is in principle reversible:

Some evidence suggests that the worst effects of Alzheimer's disease can be repaired - that memories are not destroyed, but rather become inaccessible.

Another recent study adds to this picture:

Amyloid-beta and tau protein deposits in the brain are characteristic features of Alzheimer disease. The effect on the hippocampus, the area of the brain that plays a central role in learning and memory, is particularly severe. However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off.

Researchers from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part. The scientists are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease - in part, at least.

For yet another consideration of early to mid-stage Alzheimer's as a form of dynamic blockage of memory access, you might also look at the effects of some newer anti-inflammatory treatments:

The [study from 2008] documents a dramatic and unprecedented therapeutic effect in an Alzheimer's patient: improvement within minutes following delivery of perispinal etanercept, which is etanercept given by injection in the spine.

Putting aside a discussion of the mechanisms by which this happens, the very fact that it can happen demonstrates the possibility of reversing the worst aspects of Alzheimer's. Thus memories and the working structures of the brain must remain largely intact until fairly late in the progression of the disease.

From the Monterey Herald: " Within a Northeast Ohio lab, a hairless mouse is growing an ear from the cells of a Wadsworth, Ohio, preschooler. Dr. William Landis, the G. Stafford Whitby Chair of Polymer Science at the University of Akron, is leading groundbreaking, tissue-engineering research to grow human cartilage - first in the lab, now in animals and, eventually, in patients. His work is part of a fast-developing field that could help millions of patients repair injuries, replace worn body parts or fix birth defects with tissue grown from their own cells in the not-so-distant future. ... Kyle Figuray's parents agreed to be the first area participants and donors of his otherwise useless cartilage. The healthy, friendly 5-year-old was born with a congenital defect that caused the exterior ear and ear canal on his right side to develop improperly. Typically, the malformed ear cartilage is discarded as medical waste after it's removed during the first of three procedures to craft a new ear out of rib. Instead, the tissue removed [was] placed inside a vial and shared with Landis' research team, who carefully cleansed the cells and fed them special nutrients to coax them to proliferate in the lab. A few weeks later, enough cells were available for researchers to 'seed' them onto a biodegradable, biocompatible polymer scaffold. A few days later, the seeded ear scaffold was implanted under the skin of a hairless mouse ... The mouse will be studied over the next year to determine how the cells are behaving and progressing toward normal cartilage. If all goes well, the biodegradable polymer scaffold should disappear, leaving behind only Kyle's cartilage cells in the shape of an ear. The hope is that an affected person's cells someday can be harvested, seeded onto similar polymer scaffolds and implanted under the patient's own skin in the abdomen or back until they grow into replacement tissue. At that point, the new tissue could be removed and used to replace the patient's injured or defective tissue."

Link: http://www.montereyherald.com/science/ci_17411698

Researchers examine possible molecular mechanisms for rheumatoid arthritis in a paper published earlier in the year: "Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory and destructive joint disorder that affects tens of millions of people worldwide. Normal healthy joints maintain a balance between the synthesis of extracellular matrix (ECM) molecules and the proteolytic degradation of damaged ones. In the case of RA, this balance is shifted toward matrix destruction due to increased production of cleavage enzymes and the presence of (autoimmune) immunoglobulins resulting from an inflammation induced immune response. Herein we demonstrate that a polyclonal antibody against the proteoglycan biglycan (BG) causes tissue destruction that may be analogous to that of RA affected tissues. The effect of the antibody is more potent than harsh chemical and/or enzymatic treatments designed to mimic arthritis-like fibril de-polymerization. ... The specific antigen that causes the RA immune response has not yet been identified, although possible candidates have been proposed, including collagen types I and II, and proteoglycans (PG's) such as biglycan. We speculate that the initiation of RA associated tissue destruction in vivo may involve a similar non-enzymatic decomposition of collagen fibrils via the immunoglobulins themselves that we observe here ex vivo."

Link: http://dx.doi.org/10.1371/journal.pone.0032241

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

From the Max Planck Institute: "Marriage is more beneficial for men than for women - at least for those who want a long life. Previous studies have shown that men with younger wives live longer. While it had long been assumed that women with younger husbands also live longer, [a new study] has shown that this is not the case. Instead, the greater the age difference from the husband, the lower the wife's life expectancy. This is the case irrespective of whether the woman is younger or older than her spouse. ... The mortality risk of a husband who is seven to nine years older than his wife is reduced by eleven percent compared to couples where both partners are the same age. Conversely, a man dies earlier when he is younger than his spouse. For years, researchers have thought that this data holds true for both sexes. They assumed an effect called 'health selection' was in play; those who select younger partners are able to do so because they are healthier and thus already have a higher life expectancy. ... These theories now have to be reconsidered. It appears that the reasons for mortality differences due to the age gap of the spouses remain unclear."

View the Article Under Discussion: http://www.demogr.mpg.de/en/press/1813.htm

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

There is death and then there is information theoretic death - a person who is cryopreserved is a good deal less dead than someone who went to the grave. The fine structure and data of the mind still exist, in a cold-stored stasis, and thus might be restored through foreseeable future technology. Here are some notes on the legal situation with respect to cryopreserved people: "This article series seeks to compare the legal protection of cryonics patients under their present legal status to the legal protection which would be afforded them if they were recognized as persons under the law, thinking ahead to such future time as it becomes reasonably possible to put legal and political pressure towards enhanced legal recognition of cryonics patients. The previous article examined laws that directly affect what happens to a person's body after legal death, both in the period immediately after declaration of legal death, and indefinitely thereafter. We saw that the amount of prospective autonomy a person is permitted in this regard can vary significantly from jurisdiction to jurisdiction, with more or less consideration afforded to the wishes of the person's next of kin, religious beliefs, societal norms and other public interests. Two other legal structures which can and are used by cryonicists to promote the success and timeliness of cryopreservation, maintenance, and resuscitation are wills and trusts."

Link: http://www.evidencebasedcryonics.org/2012/05/05/legal-protection-of-cryonics-patients-part-2/

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

Researchers make paralyzed rats walk through a mix of chemical stimulation and structured physical therapy; only a little regrowth in the spine occurs, but the lower spinal column can take over some of the lost functionality under the right circumstances: "a severed section of the spinal cord can make a comeback when its own innate intelligence and regenerative capacity is awakened. ... After a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical-chemical stimulation, our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles when stimulated. ... until now the spinal cord expressed so little plasticity after severe injury that recovery was impossible. ... under certain conditions, plasticity and recovery can take place in these severe cases - but only if the dormant spinal column is first woken up. To do this, [researchers] injected a chemical solution of monoamine agonists into the rats. These chemicals trigger cell responses by binding to specific dopamine, adrenaline, and serotonin receptors located on the spinal neurons. This cocktail replaces neurotransmitters released by brainstem pathways in healthy subjects and acts to excite neurons and ready them to coordinate lower body movement when the time is right. ... Five to 10 minutes after the injection, the scientists electrically stimulated the spinal cord with electrodes implanted in the outermost layer of the spinal canal, called the epidural space. ... a stimulated rat spinal column - physically isolated from the brain from the lesion down - developed in a surprising way: It started taking over the task of modulating leg movement, allowing previously paralyzed animals to walk over treadmills. These experiments revealed that the movement of the treadmill created sensory feedback that initiated walking - the innate intelligence of the spinal column took over, and walking essentially occurred without any input from the rat's actual brain. This surprised the researchers and led them to believe that only a very weak signal from the brain was needed for the animals to initiate movement of their own volition. ... newly formed fibers bypassed the original spinal lesion and allowed signals from the brain to reach the electrochemically-awakened spine. And the signal was sufficiently strong to initiate movement over ground."

Link: http://www.sciencedaily.com/releases/2012/05/120531145714.htm

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

This demonstrated technology platform has wide-ranging uses beyond muscular dystrophy. The ability to generate altered versions of a patient's own stem cell populations and then deliver them as needed could be a useful therapy for many conditions: "scientists have turned muscular dystrophy patients' fibroblast cells (common cells found in connective tissue) into stem cells and then differentiated them into muscle precursor cells. The muscle cells were then genetically modified and transplanted into mice. ... In this study, scientists focused on genetically modifying a type of cell called a mesoangioblast, which is derived from blood vessels and has been shown in previous studies to have potential in treating muscular dystrophy. However, the authors found that they could not get a sufficient number of mesoangioblasts from patients with limb-girdle muscular dystrophy because the muscles of the patients were depleted of these cells. Instead, scientists in this study 'reprogrammed' adult cells from patients with limb-girdle muscular dystrophy into stem cells and were able to induce them to differentiate into mesoangioblast-like cells. After these 'progenitor' cells were genetically corrected using a viral vector, they were injected into mice with muscular dystrophy, where they homed-in on damaged muscle fibres. The researchers also showed that when the same muscle progenitor cells were derived from mice the transplanted cells strengthened damaged muscle and enabled the dystrophic mice to run for longer on a treadmill than dystrophic mice that did not receive the cells."

Link: http://www.sciencedaily.com/releases/2012/06/120627142514.htm

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

The INDY gene in fruit flies was one of the earlier discoveries in the genetics of longevity. The initials of the name stand for I'm Not Dead Yet, an allusion to a Monty Python scene and one of many unusual names given to fly genes. You'll find a range of posts on INDY back in the Fight Aging! archives, following the research highlights over the years.

Here is an open access review paper that provides an introduction the INDY and the present state of knowledge regarding its operation when mutated to extend fly life span:

Single gene mutations that extend life span are important tools for discovering pathways underlying aging. Of particular interest have been mutations in genes that are conserved across diverse species, since they suggest common mechanisms for aging regulation. For instance, mutations in insulin signaling genes affect the life span of yeast, worms, fruit flies, and mice ... Mutations in the Indy (I'm Not Dead Yet) gene dramatically extend the life span of the fruit fly, Drosophila melanogaster. Indy encodes the fly homolog of a mammalian di and tricarboxylate transporter involved in regulating plasma and liver levels of citrate and other Krebs cycle intermediates.

...

Reduced expression of fly Indy or two of the C. elegans Indy homologs leads to an increase in life span. Fly and worm tissues that play key roles in intermediary metabolism are also the places where Indy genes are expressed. One of the mouse homologs of Indy (mIndy) is mainly expressed in the liver. It has been hypothesized that decreased INDY activity creates a state similar to caloric restriction (CR). This hypothesis is supported by the physiological similarities between Indy mutant flies on high calorie food and control flies on CR.

...

Flies, worms, and mice show similar physiological changes when INDY expression is reduced, suggesting an evolutionarily conserved role for INDY in the regulation of metabolism. ... The studies on mice further suggest protection from metabolic syndrome and insulin resistance, whether the causative factors are diet or age. INDY is thus an attractive drug target for the amelioration of metabolic disorders associated with diet or advanced age, separate from any effects on longevity.

This is one amongst many longevity-related genes, with likely many more yet to come. There is no shortage of opportunity for research groups wanting to work on the slow and incremental side of the road to the future of human longevity - to produce old-style drugs that change the long term operation of metabolism. The opportunities are there, but this is far from the best path to extending healthy human life spans.

As regular readers know, there is another path forward - the SENS vision of biotechnologies based on repair of damage rather than slowing down the rate of damage. This is likely to be no more costly [and] yet will produce at the end of the day a true cure for aging, not just a marginal benefit and a couple of extra years of life.

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

The choroid plexus is, amongst other things, a filter for cerebrospinal fluid - you might think of this role as analogous to that of the kidney as a filter for blood, though the two organs are very different in structure at every level, and the choroid plexus also produces the fluid it filters. Like all of the systems in the body and brain, the choroid plexus progressively fails in its function with age, and researchers have reason to believe that this failure contributes to conditions such as Alzheimer's disease:

An organ in the brain called the choroid plexus apparently plays a critical role in preventing the accumulation of a protein associated with Alzheimer's disease. The researchers found that the choroid plexus acts as a sort of 'fishnet' that captures the protein, called beta-amyloid, and prevents it from building up in the cerebrospinal fluid, which surrounds and bathes the brain and spinal cord. Moreover, tissue in the organ is able to soak up large amounts of the protein and may contain enzymes capable of digesting beta-amyloid.

Levels of beta-amyloid in the brain are more dynamic than their slow buildup over the years implies. You might think of the condition - and indeed the increase in amyloid levels in aging in general - as a slowly progressing imbalance of amyloid creation and clearance mechanisms rather than a slow and irrevocable deposition of amyloid. That in turn implies that a working therapy could quickly reverse all but the latest stages of the disease, when neurons are dying in large numbers.

Do rising brain levels of a plaque-forming substance mean patients are making more of it or that they can no longer clear it from their brains as effectively? ... Clearance is impaired in Alzheimer's disease. We compared a group of 12 patients with early Alzheimer's disease to 12 age-matched and cognitively normal subjects. Both groups produced amyloid-beta (a-beta) at the same average rate, but there's an average drop of about 30 percent in the clearance rates of the group with Alzheimer's. ... Scientists calculate this week [that] it would take 10 years for this decrease in clearance to cause a build-up of a-beta equal to those seen in the brains of Alzheimer's patients. The results have important implications for both diagnosis and treatment.

Here is a more recent paper that reviews what is known of the role of the choroid plexus:

Pathological Alteration in the Choroid Plexus of Alzheimer's Disease: Implication for New Therapy Approaches

In the recent years, much attention has been directed to the roles of the choroid plexus in the central nervous system (CNS) under both normal and pathological conditions. This specialized ventricular structure has recently emerged as a key player in a variety of processes that monitor and maintain the biochemical and cellular homeostasis of the CNS.

The main role of the choroid plexus is to produce cerebrospinal fluid (CSF) and to maintain the extracellular environment of the brain by monitoring the chemical exchange between the CSF and the brain tissue. This involves the surveying of the chemical and immunological status of the extracellular fluid and the removal of toxic substances as well as important roles in the regenerative processes following traumatic events. In addition to CSF, the plexus produces various peptides which can have nourishing and neuroprotective properties.

...

Morphological alterations of choroid plexus in Alzheimer's disease (AD) have been extensively investigated. These changes include epithelial atrophy, thickening of the basement membrane, and stroma fibrosis. As a result, synthesis, secretory, and transportation functions are significantly altered resulting in decreased cerebrospinal fluid (CSF) turnover. Recent studies discuss the potential impacts of these changes, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to the amyloid peptide.

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

You might recall research published last near on NRG-1 levels in naked mole-rats. Here is an update: "The typical naked mole rat lives 25 to 30 years, during which it shows little decline in activity, bone health, reproductive capacity and cognitive ability. ... Naked mole rats have the highest level of a growth factor called NRG-1 in the cerebellum. Its levels are sustained throughout their life, from development through adulthood. ... NRG-1 levels were monitored in naked mole rats at different ages ranging from a day to 26 years. The other six rodent species have maximum life spans of three to 19 years. The cerebellum coordinates movements and maintains bodily equilibrium. The research team hypothesized that long-lived species would maintain higher levels of NRG-1 in this region of the brain, with simultaneous healthy activity levels. Among each of the species, the longest-lived members exhibited the highest lifelong levels of NRG-1. The naked mole rat had the most robust and enduring supply. ... In both mice and in humans, NRG-1 levels go down with age ... The strong correlation between this protective brain factor and maximum life span highlights a new focus for aging research, further supporting earlier findings that it is not the amount of oxidative damage an organism encounters that determines species life span but rather that the protective mechanisms may be more important."

Link: http://www.mysanantonio.com/life/health/article/The-secret-of-long-life-may-be-in-a-naked-mole-rat-3543091.php

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

Research into calorie restriction has, as I'm sure you know, been picking up in pace and breadth over the past decade or so. The drug industry is interested in trying to replicate the end results without the dietary changes, which should ensure continuing funds and interest for the foreseeable future. Lowering calorie intake while still obtaining optimal levels of micronutrients is a practice that, much like regular exercise, has long term beneficial effects on health and longevity in healthy animals and people. These benefits are very reliable and exceed those that can be provided by any presently available medical technology - they also exceed the results of many of the interesting ways to extend healthy life in laboratory animals. This state of affairs won't last, given the pace of progress in biotechnology, but based on the present landscape for medical development we should expect calorie restriction and exercise to remain the best available tools for most of us for a good twenty years yet.

I noticed a good open access review paper today (the full thing is in PDF format only) that covers all of what has been learned of calorie restriction (CR) in the past decade or two. That includes the results of a fair number of human studies, what is now known of the underlying biochemistry and mechanisms, differences between intermittent fasting versus constant dietary restriction (DR), and more:

CR has been demonstrated to extend the maximal lifespan of a diverse group of species. This extension of life is maximized when: 1) the magnitude of CR is elevated to the highest possible value before inducing malnutrition and 2) the duration of CR is maximized. Animals on CR regimens exhibit a variety of improvements in overall health in general and cardiovascular health in particular. Unfortunately, the likelihood of discovering whether or not CR extends human life is rather remote due to the ethical and logistical limitations of research design. The optimal magnitude and duration of CR for humans will also likely never be known for the same reason. Nonetheless, many human CR studies have noted favorable changes in biomarkers related to cardiovascular and glucoregulatory function, which likely relate to quality of life and may relate to longevity.

...

Regarding DR, neither carbohydrate restriction nor lipid restriction extend life. However, protein restriction appears to extend maximum lifespan by 20%. Recent findings suggest that methionine restriction may be the single cause of life extension observed in protein restriction studies. Future studies should examine the effects of different magnitudes of methionine restriction on life extension.

It's pessimistic to think that optimal calorie restriction practices will not be uncovered for humans, however. Scientists can measure changing levels in biomarkers over years of calorie restriction, so identifying optimal practices really rests on the larger area of work that relates to linking biomarkers with aging and longevity. If measurable aspects of our biology can be firmly linked to future life expectancy - and there is no reason to think that the development of such biomarkers is implausible - then a whole range of medical and health practices become open to far greater optimization than is presently possible.

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