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

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

...

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

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

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

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

An unfortunate fact of life for anyone engaged in trying to persuade the world to adopt a new point of view - that crash development of rejuvenation biotechnology is a good and plausible idea, for example - is that people who are skeptical or only vaguely interested in your ideas don't tend to be vocal or engaged. So it's hard to assess their views in comparison to those people who have already been won over. This is simply a matter of priorities: when people take the time to publish their thoughts and lucid arguments, they tend to do so for their own causes, for the ideas they agree with. Time is, after all, fleeting - there are only so many blog posts and essays that can be written in any one life.

So as an advocate or activist, one has to pay attention to this hole in awareness; it's one of the things that makes advocacy a challenge. You're often none the wiser as to exactly how or why vast swathes of the population manage to be unresponsive to your message and outreach efforts. They know, but getting them to tell you is like blood from a stone.

On this topic, I see that Aubrey de Grey of the SENS Foundation recently gave a talk in Baltimore on SENS and the path to rejuvenation biotechnology. One of those attending was Kavan Peterson, a writer from ChangingAging, which is something of a pro-aging organization - both in the sense of empowerment and opposition to ageism, which are noble causes, but also in the less desirable sense of apologism for aging. There are already far too many talking heads trying to persuade the world that progressively accumulating pain, suffering, and loss of function are just fine and dandy. In any case Peterson, unlike most skeptics, took the time to write. So we should take the time to learn from that:

The Immortal Life? An Evening With Aubrey de Grey

I am skeptical of de Grey's work and I'll use his own introduction to explain why: "It may seem premature to be discussing the elimination of human aging as a cause of death, when so little progress has been made in even postponing it says Aubrey de Grey." That's right - despite all the marvels of modern medical science, there is absolutely zero evidence that any known treatment has ever extended human life by a single day. Immortality is as fantastical an idea today as it was in ancient times.

My Evening With Aubrey de Grey

I'd like to think of ChangingAging.org as the preeminent pro-aging blog so it was a great opportunity to talk to the world's leading anti-aging advocate. And surprisingly I came away with the impression that although our rhetoric is wildly divergent - as divergent as anti- vs pro-aging rhetoric can be - we share similar goals.

First, where we diverge - as our masthead says, we look at human aging "as a strength, rich in developmental potential and growth." De Grey argues aging is "obviously, unequivocally humanity's worst problem."

That's a big difference. But lets look at our goals.

You should read the rest of it; this is an example of the type of person we'd like to persuade to support SENS and the broader field of work on repair-based strategies to reverse aging. Separately, I noticed another blog post from a different attendee, one who falls into the category of peripherally interested, I believe. She made this remark:

I asked the question: "There are assumptions in your theory, that the patient will get to the doctor on time, that the doctor is well trained in this new technology, and that the insurance companies will pay for these services." His answer was that his main focus is on the biological aspect and that these issues will come up and will need to be addressed at some point.

Also worth learning from.

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

There's an article over at Reason Magazine today that calls out one example in a pattern of abuse of meaning that I've long found threatening. Attempts to fundamentally rework the meaning of a basic and important word are one of those little fragments of 1984 that manage to drift into the real world, an unsavory activity in which the meaning of the word is both kept and entirely inverted at the same time. I think the following quote captures the essence of this particular case:

Lawler, a member of President George W. Bush's controversial Council on Bioethics, tried to make the case that using technology to radically extend human lifespans, and boost human intellectual, emotional, and physical capacities, will end in coercion. Those who don't want to take advantage of the kinds of enhancements that biotechnology, nanotechnology, and cognitive technology will offer, argues Lawler, will ultimately not have a choice about using them. ... But is that so? If anyone should be concerned about coercion, it is the transhumanists who rightly fear that bioconservatives like Lawler will try to use the power of the state to halt the research that would lead to the development of enhancements would enable them to improve their life chances and those of their children.

Shades of Freedom is Slavery march through all too many minds, methinks. That is a real threat, as halting and slowing research in the life sciences is something that the bureaucrats of the modern state are very good at indeed. That people carefully try to invert the word "coercion" to mean "the existence of freedom of choice that I personally do not approve of" is also a threat, as freedom of choice and freedom from coercion are the deep roots of wealth and technological progress. Without them, you end up living in something akin to the backward ruins and ruined, predatory culture of the final years of the Soviet Union.

Freedom is fundamental to transhumanist ideals - such as developing the means to greatly extend youthful life span through biotechnology. Freedom is vital for the research and research community needed to open these new doors:

Freedom of research is, in essence, economic freedom, which is no different from personal freedom - the freedom to invest and work in whatever arrangements you can freely agree upon with other people. The most rapid progress occurs in free marketplaces, free for the exchange of ideas, free for association with others for mutual benefit, free for the exchange of goods. Any and all interference by centralized entities - such as governments - is inefficient and serves only to slow things down, make goods more expensive, and ensure that some research never happens at all.

Further, freedom is the very essence of transhumanism itself, which is no more than the human imperative to create new choices where before there was nothing. Having a choice today in an area where there was no choice yesterday is an increase in your freedom, and building those new choices - these new freedoms - is exactly what humanity achieves through technology:

Transhumanism, make no mistake, is just a fancy name for common sense. Change for the better is good, right? Common sense. It's what we humans do in our scattered finer moments - we work to change things for the better. It's common sense to fetch in the harvest on wheels rather than on foot, and it's common sense to repair the biomolecular damage of Alzheimer's before the mind begins to rot. It's common sense to build perfect immune systems from nanomedical robots, and it's common sense to develop the technologies of regenerative medicine to their logical end. It takes work, but what is work compared to a world of suffering? Choosing not to attain these goals makes about as much sense as standing out in the rain to spite yourself.

The Soviet Union may be gone in all but the longer memories, but there is no shortage of people who would strive to rebuild it again, today, in their country, one piece at a time. There are so many petty would-be totalitarians in this world, each laboring under the belief that central control of the matters they care about will work - this time! - if it is just done their way. The real danger of centralized government is that sooner or later, those would-be totalitarians get their hands on their ability to do real harm by attempting to enact their visions.

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

An example of present work in growing skin from stem cells: scientists "are participating in research to study how to make use of the potential for auto regeneration of stem cells from skin, in order to create, in the laboratory, a patient's entire cutaneous surface by means of a combination of biological engineering and tissue engineering techniques. Skin is a tissue that naturally renews itself throughout our lives thanks to the existence of epidermic stem cells. ... We have found that this regenerative potential can be preserved in vitro (in the laboratory) if the cells are joined and become part of generated skin using tissue bioengineering techniques. ... The researchers have already been able to join together these epidermic stem cells into skin created by means of bioengineering, and they have observed that the cells preserve the regenerative potential that they normally have in our skin. That is, using a small biopsy from a specific patient, they can generate almost the entire cutaneous surface of that individual in the lab. ... The regenerative capacity of epidermic stem cells in these conditions is overwhelming, and it leads to the possibility of using these cells as a target for even more complex protocols, such as gene therapy. ... In fact, these researchers have already demonstrated, at the pre-clinical level, that it is possible to isolate epidermic stem cells from patients with different genetic skin diseases, cultivate them and, using molecular engineering as a first step, incorporate the therapeutic genes into each patient's genome to take the place of the one that the patient does not have or that functions abnormally. Afterwards, in the second step, the stem cells would be assembled into patches ready to be transplanted onto the patients."

Link: http://www.physorg.com/wire-news/80303525/bioengineering-to-repair-and-generate-healthy-skin.html

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

Another in a series of articles on this topic from Singularity Hub: "The blind in Europe have reason to rejoice, the world's most advanced artificial retina has just received the CE Mark, approved for use in new patients. The Argus II, developed by Lawrence Livermore National Laboratory and marketed by Second Sight, is on sale in the EU, but still awaiting FDA approval here in the US. Luckily, clinical trials are already underway and we could get the amazing device here soon. With the Argus II, blind patients use an external camera to pick up video that is wirelessly transmitted to an electrode array surgically implanted in the eye. While full vision is not restored, the 60+ electrodes allow for some distinction of outlines and other basic shapes. Definitely an improvement over blindness. ... a camera embedded in a pair of glasses records the world in front of the patient. A wearable computer takes that image and transforms it into a basic series of impulses. That pattern is transmitted to the Argus II implant which rests inside the eye, and which is attached to the back of the eye through an electrode array. ... Although software improvements may arrive first, hardware upgrades are also on the horizon. The Argus II operates with about 60 electrodes in its array. That's 60 points of data for your eye to interpret. The Argus III, currently under development at LLNL, should have 200+ electrodes. Perhaps considerably more. It will take a thousand or so to make out human faces accurately, but the Department of Energy is pushing LLNL towards that goal, and beyond. As slow as the progress in artificial retinas has been, it shows no sign of stopping. There are other projects outside of the Argus series, at least two (one in MIT, another in Germany) show serious promise, and even have superior qualities to the Argus in some respects. I have no doubt that we could, eventually, reach a resolution that equals that of the human eye. Perhaps, with a different kind of interface, we could even see in greater detail than nature intended."

Link: http://singularityhub.com/2011/03/08/artificial-retina-that-lets-the-blind-see-again-more-great-videos-of-the-argus/

This is an open access report in book format that delves into the factors that cause regional variations in life expectancy and rates of age-related disease - and thus longevity - in the first world. Given its origins, don't expect to see much on the stifling regulation that raises prices and reduces quality and innovation in medicine, but most of the other important contributing factors are addressed: "Over the past 25 years, life expectancy has been rising in the United States at a slower pace than has been achieved in many other high-income countries. Consequently, the United States has been falling steadily in the world rankings for level of life expectancy, and the gap between the United States and countries with the highest achieved life expectancies has been widening. International comparisons of various measures of self-reported health and biological markers of disease reveal similar patterns of U.S. disadvantage. The relatively poor performance of the United States with respect to achieved life expectancy over the recent past is surprising given that it spends far more on health care than any other nation in the world, both absolutely and as a percentage of gross national product. Motivated by these concerns, the National Institute on Aging requested that the National Research Council convene a panel of leading experts to clarify patterns in the levels and trends in life expectancy across nations, to examine the evidence on competing explanations for the divergent trends, and to identify strategic opportunities for health-related interventions to narrow this gap."

Link: http://www.ncbi.nlm.nih.gov/books/NBK62369/

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

Via FuturePundit, the estimates for recent research funding: "The U.S. invested $139 billion last year in health research from all public and private sources, according to Research!America's latest annual estimate. That amount represents only 5.6% of the $2.47 trillion overall U.S. health spending in 2009 [which] varies no more than 0.2% from 2005 levels. ... We are all growing old. We are all aging and our parts are breaking down and wearing out. A portion of those billions of dollars flows toward science technologies that will eventually put an end to aging. Human bodies will become as repairable as cars. Replacement organs, cell therapies, gene therapies, and even nanobots will, at some point in the 21st century, halt and reverse the process of aging. Will you still be alive when that day is reached?" As has always been the case, funding for research is a tiny percentage of the flows of money in our culture. Funding for aging research is a tiny fraction of the figures given above, and funding for engineered longevity is in turn a tiny fraction of aging research. To fully realize the Strategies for Engineered Negligible Senescence in mice in the laboratory would probably cost in the vicinity of $1-2 billion over a decade or two. Food for thought.

View the Article Under Discussion: http://www.futurepundit.com/archives/007557.html

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

A new study discovered that regular consumption of fruits and vegetables greatly helps in reducing the risk of Ischemic Heart Disease.

Nowadays, more and more people are suffering from coronary artery diseases, also medically known as Ischemic Heart Disease (IHD). Ischemia happens when blood is restricted from entering a specific area, which causes the structures in that area to necrose, or to die, since blood carries with it life-giving oxygen and other essential nutrients. In the case of ischemic heart disease, blood supply is restricted from entering the heart.  Because of this, problems start to arise.

The development of Ischemic Heart Disease is dependent on the health of the blood vessels.  Arteries, for example, are the main sites for fatty plaque build-up.  When a person’s bad cholesterol level is too high, this would result to the accumulation of fatty deposits in the linings and the walls of the arteries.  Over time, this build-up will impede blood supply which will result to ischemia.  This is the main reason why health professionals have always emphasized the need to consume a healthy diet. Other risk factors for the development of IHD includes a family history of the said disease; when there is too much fat content in your daily diet; smoking; hypertension, and even the occurrence of a previous stroke or heart attack.

In the United States today, heart disease is the primary cause of death amongst the entire population. The primary cause of this ailment remains unknown but the number of risk factors is considerably high. It has been clear lately that the treatment of abnormalities of the body’s lipids can delay the progress of a possible atherosclerosis.

There are particular tests that can be done to know how much your ischemic heart disease has grown. Several diagnostic tests include electrocardiogram, echocardiogram, blood studies, x-rays, coronary angiogram and many more.

Eat More Fruits and Veggies

A recent study done in Europe investigated the relationship between the disease and diet and found out that those who get to eat a larger amount of vegetables and fruits seem to have a lower risk of suffering from ischemic heart disease. The said study was published online last January 19 at the European Heart Journal.

Their data showed that those who take in at least eight servings of vegetables and fruits everyday had about 22% lower risk of dying from Ischemic Heart Disease or IHD compared to those who eat less, or just about three servings a day. The lead author of the study, Dr. Francesca Crowe, stated that their research included more than 300,000 people from 8 different countries all around Europe.

According to Dr. Crowe, the bottom line of their analysis only says that if people would consume greater amounts of vegetables and fruits, then this would lead to a reduction in the number of IHD cases. However, she emphasizes that it is still important for individuals to live a healthy lifestyle by exercising and avoiding unhealthy habits such as smoking, substance abuse and drinking to the point of intoxication.

Natural Ways to Prevent Ischemic Heart Disease

Ischemic heart disease is considered to be a silent killer.  Sometimes, you go through life not knowing anything and when it hits you, it takes you aback. It is important, therefore, that you take note of these general measures that can help you prevent them from happening. The following are some of the most important ways that you can fight IHD, or any form of disease for that matter:

• Get Some Regular Exercise. Exercise can help a lot in improving your blood flow and even reduce the occurrence of abnormal heart rates. This can include simple changes in your routine like probably taking the stairs instead of getting on the elevator, or walking the four blocks to your favorite library instead of taking the cab. But of course, it is much better if you can commit to doing regular exercise that you would already consider as a habit like probably walking or jogging a few minutes every other day.
• Maintain A Healthy Diet. It is really very crucial that you watch what you eat when you are trying to monitor your cholesterol levels. You must be able to reduce it to a certain amount that would reach normalcy. Eat foods that are low in cholesterol and fats. It is also very important that you remember staying away from fats that are saturated. Your diet must include a lot of fruits and vegetables so that maintaining your ideal body weight would be less of a hassle.
• Live a Healthy Lifestyle. As much as possible, try to avoid smoking and avoid, or limit, your alcohol intake. It is very essential for you to always get to monitor your blood pressure and always keep things in control. Try to be happy all the time so that you will not be prone to heart attacks due to too much stress. If you are currently overweight, then it is about time to start thinking about lowering your total weight and bringing it back to normal.
• Talk to your Doctor. If you are overly worried with your heart’s condition, especially when you realize that you are not growing any younger, then you must not put off having regular check-ups with your doctor. It would not hurt that much if you would take the time to see him on a regular basis. These visits could include some tests or examinations that would try to figure out any possible threats to your heart and the rest of your body. Early diagnosis and treatment of Ischemic Heart Disease can definitely lead to total recovery. Through the years, lots of research has been done to promote and encourage fast and effective treatments for this ailment. It is very essential that you maintain a healthy lifestyle especially when it comes to making certain important changes in your diet and level of activity.

Remember this: a failure of the heart to function will lead to the loss of function of the other organs as well.  A deteriorating heart will cause a cascade of events which can sometimes prove to be fatal.  So if you love the people around you, do them a favor by loving your heart first – and then all else will follow.

Sources
eurekalert.org
rxmed.com
populararticles.com
mayoclinic.com

Discuss this post in Frank Mangano’s forum!

A study conducted by a team of Australian researchers found that the increased supplementation of vitamin D and calcium can result to a significant increase in bone density and reduction in osteoporosis risk.

There are approximately 75 million people who suffer from the health condition in Japan, Europe and the United States. And according to statistics, women are four times more likely to develop the health condition than men.

A study conducted by a group of Australia researchers found that the supplementation of 400 IU of vitamin D3 and 800 milligrams of calcium can notably increase the bone strength and density of peripubertal female identical twins. The study was published in Osteoporosis International, a publication dedicated to discussing the issues on osteoporosis. The health condition is characterized by low bone density resulting to an increased risk of bone fracture and deformation of the wrist, spine and hip area.

The traditional approach in preventing osteoporosis aims to increase the person’s bone mass. And this can be achieved though calcium and vitamin D supplementation at pubescent years and in pre-menopausal age where the osteoporosis risk is noted to be higher. The bone build-up during the puberty years accounts to around 35 percent of a person’s adult bone mass.

Vitamin D and Calcium:  Effects on Osteoporosis

The researchers from the Australian Catholic University gathered a group of 20 identical twins and divided them into two groups. The first group was given a combination of vitamin D and calcium food supplement while the other served as the placebo group. The study lasted for six months and was the first to use pQCT, or peripheral quantitative computed tomography, to examine and measure the responses of the study participants’ bone structure. They found that the combination of vitamin D and calcium resulted to an increase in the study participants’ bone strength and bone density in the arm and shinbone by 4 to 66 percent depending on the specific bone area tested.

Earlier studies had already provided scientific evidence that calcium and vitamin D intake improves bone density and strength. A randomized trial conducted by a team of scientists from the University of Sheffield in the UK, for example, found similar results. The study was published in the February issue of the American Journal of Clinical Nutrition. In the study, the researchers observed that the supplementation of 792 milligrams of calcium resulted to an increase in the study participants’ bone mineral content and bone density. They also observed that the effects were reversed once the supplementation stopped.

The annual sales for calcium food supplements was about $993 million in 2004 according to the information provided by the Nutrition Business Journal. And this is projected to increase to $22 billion by 2013 according to the survey conducted by the Ipsos Public Affairs for the Council of Responsible Nutrition.

The Relationship between Calcium and Vitamin D

Calcium is an essential nutrient needed for the essential function of the nerves, muscles and the heart. The inadequate supply of calcium in the body often results to the development of osteoporosis. Studies show that the lack of calcium intake in early life can result to low bone density and increased bone fracture rate in adulthood. National surveys, however, found that people are not satisfying their daily calcium recommendation to promote and maintain bone health.

The recommended calcium intake for children and young adults aged 9 to 18 years is 1300 milligrams.  This is according to the National Academy of Science. In order to ensure that the risk of developing osteoporosis is decreased, it is important therefore, that one’s daily calcium intake is in accordance with the recommended intake. However, simply eating foods rich in calcium and taking calcium supplements is not enough. The body needs the help of precursors to promote calcium absorption so that it can be effectively utilized by the body. The active form of vitamin D is calcitriol. The substance is responsible for calcium absorption and the storage of calcium in the bones.

There are three ways a person can satisfy his vitamin D needs: these are through the skin, from supplementation and from diet. Vitamin D can be produced by exposing the body to sunlight. Exposure to the sun without any protection for a minimum of 15 minutes in a few days a week can give the body enough vitamin D to function properly. Medical experts also suggest a minimum of 400 to 600 IU of vitamin D a day from food and food supplements to promote better calcium absorption. The richest natural sources of vitamin D are liver, saltwater fish and egg yolks.

Natural Ways to Prevent Osteoporosis

Increasing the intake of vitamin D and calcium is the first step to reducing the risk of developing osteoporosis. The second step is to exercise regularly. Studies found that regular exercise, together with increased calcium and vitamin D consumption, can significantly reduce a person’s osteoporosis risk. Weight training can improve a person’s metabolism, tone the muscles and helps in maintaining health and strong bones. It is not important what kind of exercise a person does. But what is important is its frequency, intensity and consistency. Aerobics and weight training for a minimum of thirty minutes will make the bones stronger. Stair climbing, hiking, jogging and even dancing can produce enough movements keep the bones healthy and strong.

Eating foods rich in essential fatty acids is essential in keeping the intestinal lining healthy and more capable of absorbing minerals from the foods we eat. Vitamin A promotes better absorption of minerals like magnesium and calcium while antioxidants from natural sources helps reduce the risk of developing osteoporosis by protecting the bones from the damage caused by free radicals. Fruits and vegetables can also improve bone density by supplying the body with potassium and magnesium.

Get into the habit of having your bone density regularly checked. This is an important preventive measure to avoid the onset of osteoporosis. Bone density test will evaluate your osteoporosis risk and give you recommendations of whether you need to get more supplementation of vitamin D and calcium. Note that osteoporosis can remain undetected for years until you experience obvious symptoms like serious bone fracture and bone deformation. This makes early diagnosis very important.

Sources
nutraingredients.com
ncbi.nlm.nih.gov
jacn.org
nutraceuticalsworld.com
niams.nih.gov

A new study from Los Angeles has shown that seniors who have a poor quality of sleep also experience depression and other negative symptoms.

Good sleep is important for everyone, but a new study shows that the necessity of quality sleep is especially crucial when it comes to seniors.  A recent study published in the Journal of the American Geriatrics Society showed that if seniors don’t sleep well each night, it could decrease their overall quality of life.

The research focused on residents of Assisted Living Facilities in Los Angeles.  The study followed up with them for 6 months and traced their sleep patterns and emotional states.  The researchers found that the 65% of seniors that reported that they slept poorly also have increased levels of depression and poor quality of life.

Of the seniors studied, sleep was about 5 hours on average.  The people also reported “trouble sleeping” as defined by the Pittsburgh Sleep Quality index. This includes waking up in the middle of the night, or taking more than 30 minutes to fall asleep.  The Pittsburgh Sleep Quality Index is a free test that measures your quality of sleep. It only takes 5 minutes to complete and can be found here.

Those who reported poor sleep in the Los Angeles study were not only more depressed but also more likely to need help with common everyday activities.  Jennifer Martin, PhD, of the University of California, Los Angeles and VA Greater Los Angeles Healthcare System stated, “We cannot conclude that poor sleep truly causes these negative changes; however, future studies should evaluate ways to improve sleep in ALFs to see if sleeping better might improve quality of life, delay functional decline and reduce risk of depression.”

The study does mention that there are effective methods for improving sleep, for example, bright light therapy.  Other methods for improving sleep include spending time outside during the day, resisting alcohol or caffeine before bed and avoiding smoking.

Sources:
medicalnewstoday.com
sleep.pitt.edu
health.com

Discuss this post in Frank Mangano’s forum!

Maria Konovalenko on the study of the often large life span differences between similar species - or rather the lack of such research work in comparison to other fields of life science: "Here's this quite simple idea: to take two species similar in size and basic biology, but having a substantial difference in longevity, and figure out what's the reason for this difference. What are the distinctions in the mechanisms of aging and stress resistance? It's desirable to carry out this work in various species. However, not a lot of people are excited about this simple idea. Even the genome of the famous naked mole rat has not been sequenced yet, although many people believe it's got 'negligible' senescence. For now all that we have is negligible funding of evolutionary-comparative biology of aging. Moreover, previously obtained results are put into cold storage. ... And here comes the main question in biogerontology. Why is the research into the fundamental mechanisms of aging so scarcely funded?" Aging and longevity research in general receives very little funding and attention in comparison to its importance to the future of human health. This state of affairs is slowly changing, but not fast enough for my liking.

View the Article Under Discussion: http://maria-konovalenko.typepad.com/blog/2010/06/the-main-question-in-biogerontology.html

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Why not aim to improve on blood? Its primary function is to carry oxygen, and it has evolved to do the bare minimum necessary on this front - separate any part of the body from a supply of oxygen for a minute or so and you're in trouble. It would be nice, for example, to have blood with a reserve capacity of a few hours, achieved using nanomachines that store the surplus oxygen that the body doesn't otherwise extract from air breathed in. Even if the heart stopped or blood stopped flowing in some vital tissue, you'd have those few hours to seek medical help. Here is a gentle first step towards the technologies of better blood: researchers "designed tiny, gas-filled microparticles that can be injected directly into the bloodstream to quickly oxygenate the blood. The microparticles consist of a single layer of lipids (fatty molecules) that surround a tiny pocket of oxygen gas, and are delivered in a liquid solution. ... report that an infusion of these microparticles into animals with low blood oxygen levels restored blood oxygen saturation to near-normal levels, within seconds. When the trachea was completely blocked - a more dangerous 'real world' scenario - the infusion kept the animals alive for 15 minutes without a single breath, and reduced the incidence of cardiac arrest and organ injury. The microparticle solutions are portable and could stabilize patients in emergency situations, buying time for paramedics, emergency clinicians or intensive care clinicians to more safely place a breathing tube or perform other life-saving therapies. ... The microparticles would likely only be administered for a short time, between 15 and 30 minutes, because they are carried in fluid that would overload the blood if used for longer periods ... the particles are different from blood substitutes, which carry oxygen but are not useful when the lungs are unable to oxygenate them. Instead, the microparticles are designed for situations in which the lungs are completely incapacitated. ... Intravenous administration of oxygen gas was tried in the early 1900s, but these attempts failed to oxygenate the blood and often caused dangerous gas embolisms. ... We have engineered around this problem by packaging the gas into small, deformable particles. They dramatically increase the surface area for gas exchange and are able to squeeze through capillaries where free gas would get stuck."

Link: http://www.eurekalert.org/pub_releases/2012-06/chb-ilo_1062212.php

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

Researchers have regrown teeth in rats by manipulating existing stem cells: "a new technique [can] orchestrate the body's stem cells to migrate to three-dimensional scaffold that is infused with growth factor. This can yield an anatomically correct tooth in as soon as nine weeks once implanted in the mouth. ... These findings represent the first report of regeneration of anatomically shaped tooth-like structures in vivo, and by cell homing without cell delivery. ... By homing stem cells to a scaffold made of natural materials and integrated in surrounding tissue, there is no need to use harvested stem cell lines, or create a an environment outside of the body (e.g., a Petri dish) where the tooth is grown and then implanted once it has matured. The tooth instead can be grown 'orthotopically,' or in the socket where the tooth will integrate with surrounding tissue in ways that are impossible with hard metals or other materials. ... A key consideration in tooth regeneration is finding a cost-effective approach that can translate into therapies for patients who cannot afford or who aren't good candidates for dental implants. Cell-homing-based tooth regeneration may provide a tangible pathway toward clinical translation."

View the Article Under Discussion: http://www.dentistryiq.com/index/display/article-display/0045494294/articles/dentisryiq/industry/2010/05/body_s-stem_cells.html

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Via ScienceDaily: researchers "have identified two key regulatory proteins critical to clearing away misfolded proteins that accumulate and cause the progressive, deadly neurodegeneration of Huntington's disease (HD). ... It's a lead we can vigorously pursue, not just for Huntington's disease, but also for similar neurodegenerative conditions like Parkinson's disease and maybe even Alzheimer's disease. ... In HD, an inherited mutation in the huntingtin (htt) gene results in misfolded htt proteins accumulating in certain central nervous system cells. ... [Researchers] focused on a protein called PGC-1alpha, which helps regulate the creation and operation of mitochondria, the tiny organelles that generate the fuel required for every cell to function. ... It's all about energy. Neurons have a constant, high demand for it. They're always on the edge for maintaining adequate levels of energy production. PGC-1alpha regulates the function of transcription factors that promote the creation of mitochondria and allow them to run at full capacity. ... the mutant form of the htt gene interfered with normal levels and functioning of PGC-1alpha, [and] elevated levels of PGC-1alpha in a mouse model of HD virtually eliminated the problematic misfolded proteins. ... PGC-1alpha influenced expression of another protein vital to autophagy - the process in which healthy cells degrade and recycle old, unneeded or dangerous parts and products, including oxidative, damaging molecules generated by metabolism. For neurons, which must last a lifetime, the self-renewal is essential to survival. ... Mitochondria get beat up and need to be recycled. PGC-1alpha drives this pathway through another protein called transcription factor EB or TFEB. ... If you can induce the bioenergetics and protein quality control pathways of nervous system cells to function properly, by activating the PGC-1alpha pathway and promoting greater TFEB function, you stand a good chance of maintaining neural function for an extended period of time."

Link: http://www.sciencedaily.com/releases/2012/07/120711141853.htm

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Xenotransplanation is the use of animal organs, possibly genetically modified, in place of human organs for transplantation in cases of organ failure or damage. This is one of the developing technologies that will compete with electromechanical or bioartificial organs and tissue engineering of whole organs to make organ replacement a far more viable, effective, and low-cost prospect than it is today. To my eyes xenotransplantation was always going to be a transitional technology, economically viable for a period of years in which tissue engineering was still finding its feet, but the development of decellularization has made animal organs look like a far more interesting long term source of raw materials.

a valve from a human or animal donor is removed of all cells using tissue engineering, so that only its outer framework remains. This valve matrix is then colonised with cells that have been obtained from the blood of the recipient and propagated. Within a few weeks, a quasi-natural heart valve then emerges in this bioreactor, that exhibits no rejection response or other faults, but instead grows with the patient after the implantation. ... Recellularization makes xenotransplantation a much more viable technology to fill the tissue engineering gap prior to the ability to grow complex organs from scratch.

The use of the patient's own cells in a donor scaffold removes issues of immune rejection, wherein the patient's immune system attacks and destroys the donor organ. When immune rejection is removed from the equation, not only does the entire process become much safer and cheaper, we are left with the extracellular matrix organ scaffold as the actual raw material required. A full organ scaffold is presently too complex for researchers to construct from scratch, and even when this can be done at some point in the next decade or two, it will be expensive for a time thereafter. Obtaining the decellularized scaffolds from human organs puts you right back to where you started with the difficulties of sourcing donor human organs when needed, but using animal organs can work around that issue.

I noticed a recent article that discusses the timelines for present work on xenotransplanation without decellularization, which is largely focused on transferring cells and small sections of tissue rather than whole organ structures. Organs are clearly on the agenda, however:

During the past decade xenotransplantation, the use of animal organs, tissues or cells in humans, has made great advances. Due to the fact that more and more genetically modified pigs are available with genes to protect them from human immune response, has alleviated earlier problems in helping humans to accept such transplants. ... at this time the longest time of survival for pig organs in non-human primates varies from a few days in lung transplants to approximately 6-8 months in hearts transplants. Although research is still years away from conducting human trials of solid organ transplants of this nature, lifesaving transplants of a pig heart or liver could pose as an alternative solution until a human organ becomes available. At present researchers are investigating strategies to incorporate human anticoagulant or antithrombotic genes into genetically modified pigs, and additional genes to regulate the human inflammatory response.

...

The authors also discussed in terms of organs, that stages of other strategies are currently more advanced than xenotransplantation, such as left ventricular assist devices for cardiac support. However, they agree that given time, transplanting a pig's heart will prove to be the better option compared to using a mechanical device.

...

Although remaining issues are delaying clinical implementation, experimental results obtained with pig islet, neuronal-cell, and corneal xenotransplantation have been encouraging. With new genetically modified pigs becoming available that are likely to improve the outcome of cellular and corneal xenotransplantation further, we believe that clinical trials will be justified within the next 2-3 years. No safety concerns that would prohibit such clinical trials have been reported...With regard to pig tissues and cells, as opposed to organs, it would seem that clinical xenotransplantation could soon become a reality.

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Something to think about: outstanding success for the SENS Foundation and its mission would look something like the assured availability of $100-300 million for research and development. That much money tends to build the successes and cachet needed to attract more of the same. To get to this point from where the Foundation stands now (a yearly budget around $1 million for the SENS Foundation, and an unknown but likely smaller level of unaffiliated funding for the same goals) might take twenty years of steady growth and success, with the end result being a substantial persuasion and conversion of the present research and funding culture for medical development. That wouldn't mean that the SENS Foundation would be a $100 million giant, or even necessarily still exist, but it would give rise to a diverse and competitive community that inherits the founders' values and goals - to defeat aging by building rejuvenation biotechnology more or less as presently envisaged in the SENS platform.

So what happens if a fellow with a net worth of $100-300 million becomes a zealot for the cause, overnight perhaps, and decides to put his net worth behind the SENS cause because without life and health, what is money? I use the world zealot in the best possible way here: someone who values the cause greatly enough to spend more time and money than most other people consider reasonable - but in this case is entirely justified, given the present harms caused by aging. But what happens if the community acquires such a zealot? To my eyes it looks like we would gain two decades of headway, and projects that would otherwise languish for twenty years would commence immediately. In a pattern of growth that is limited only by the level of investment - which is exactly where rejuvenation biotechnology is today - everything in the timing hinges on when the money arrives.

(It's a little more complex than this, of course, given that biotechnology is rapidly improving and costs for any given life science research project will fall rapidly over time - but you get the picture. Early money is still very much better than waiting).

The interesting question is why this doesn't happen: there are a fair number of very wealthy people in the world, and logic suggests that the best possible use for much those resources from their individual perspectives would to buy more life - since we are now in an age in which it is possible to make a run at buying significantly more life. What is wealth to the sick or the dead when it comes to it? But I don't think that this is a "why don't more people support engineered longevity?" sort of a question. My suspicion is that it is not just longevity science that looks in vain for wealthy zealots, but that in general any grand cause that people can feel very strongly about also lacks wealthy zealots. It seems to me that there is in fact little overlap between the small population of zealots for a cause, people willing to devote their working life and significant resources to a grand project, and the small population of very wealthy people, those with a net worth of $100 million and up.

We can speculate as to why this might be. For example, I might try to argue that the sort of person who can successfully run the long and unlikely process of becoming very wealthy is the sort of person who doesn't think about what they can do with money. They are not doing what they do for money, and the process is their passion. Someone who was a zealot for a cause would have stepped off that process long before reaching the possibility of attaining a very high net worth. Having a mere seven figure net worth for most people enters the territory of being able to prioritize volunteering over working, or funding a small mission in their favored charity. The temptation to break off and work on doing good rather than continually doubling down and doubling down on the process is ever there.

Or to put it another way, the passion for the process that will make a person wealthy takes up the much the same mental space as the passion for a cause: there are only so many hours in the day, and only so much attention that a person can give to any one set of information. So you are unlikely to see a person who has (a) accomplished the necessary devotion to work and process for a shot at becoming very wealthy, but also (b) put in the necessary work and process to become a zealot.

Or to put it yet another way, neither becoming exceedingly wealthy nor becoming a zealot are things that just happen one day out of the blue. They are each a fair way down their own different paths of effort, realization, and specialization.

This sort of thinking is the flip side of considering persuasion, high net worth philanthropy, and fundraising in general. It suggests that persuasion is exactly necessary because, for one, the odds of a funding source emerging from the pool of already-persuaded-and-fully-into-it supporters is pretty remote. Secondly, the odds are equally low that any particular high net worth individual or organization will suddenly get the picture of their own accord and begin pouring out money like water. These are different worlds, different views, different life courses that touch at few points - so people must set out to deliberately try to bring them together.

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

The second volume of the new open access journal Pathobiology of Aging and Age-related Disease is available online. I thought I'd point out one of the papers, which argues that the biology of long-lived mouse species should be considered evidence for the importance of chronic inflammation in determining life span.

Growth hormone, inflammation and aging

Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1) constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor / growth hormone binding protein knockout (GHRKO) mice characterized by GH resistance live significantly longer than genetically normal animals.

During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines.

This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

Regular readers will recall that there is a mountain of evidence to link aging and chronic inflammation. If you have higher levels of inflammation, you will have a worse - and usually shorter - time ahead. It causes damage, and that damage adds up; the easiest way in younger life to raise inflammation levels is to become fat, as visceral fat tissue works a number on your metabolism. But everyone's immune system runs off the rails given time, falling into a state wherein it is constantly roused but increasingly ineffective in its designated jobs. Many of the aspects of aging are clearly connected to immune system decline: raised levels of inflammation, increased numbers of senescent cells, increased risk of cancer, and more.

This all argues for some form of safer, more mature version of the immune system reboot therapies that can presently be accomplished, but are not available outside of trials at this time. A large fraction of the immune system's failure with age stems from structural issues: it has evolved to be very, very good at its job in early life, but at the cost of inevitably and predictably failing as it runs out of capacity later on.

Throughout our lives, we have a very diverse population of T cells in our bodies. However, late in life this T cell population becomes less diverse ... [one type of cell] can grow to become more than 80 percent of the total [T-cell] population. The accumulation of this one type of cell takes away valuable space from other cells, resulting in an immune system that is less diverse and thus less capable in effectively locating and eliminating pathogens.

But if the slate could be wiped clean (achieved by chemotherapy at the present time, which is far from ideal) and the immune system repopulated (using stem cells to generate a population of patient-matching immune cells), then this issue vanishes, and people could benefit from a strong immune system for decades longer than is presently the case. That would likely make a significant difference to the course of later life, even in the absence of other advances in medical technology.

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

A look at what comes after merely targeting cancer cells: "Several decades from now we hope to have sophisticated medical nanorobots, produced by molecular manufacturing, that can enter cells, analyze the state of the cell, and initiate appropriate therapy, such as killing cancer cells. A team of scientists [has] taken an important step in that direction by demonstrating a synthetic circuit that, when incorporated into a cell, detects the presence or absence of five specific small RNA molecules,processes that information, and then, based upon that result, either kills or does not kill the cell. ... [The] long-term goal is to construct biocomputers that detect molecules carrying important information about cell wellbeing and process this information to direct appropriate therapeutic response if the cell is found to be abnormal. ... The researchers constructed what they describe as a 'classifier' gene circuit that is transiently expressed inside a cell and then integrates information from five molecular markers to determine the state of the cell, and then produces a protein that sets off the cellular suicide cascade if the cell is determined to be cancerous. The DNA circuit they constructed contains numerous control sequences chosen from standard genetic engineering toolkits that respond to specific miRNAs such that only the combination that identifies the particular cancer cell line used in the experiments activates the circuit and triggers the onset of cellular suicide. The results presented do show some false positives and some false negatives, so further optimization of the genetic circuit would be needed. Nevertheless, the results are impressive. Also, in principle, this method could be adapted to different cell types by choosing the combination of miRNAs appropriate to distinguish that cancerous cell from neighboring cells."

Link: http://www.foresight.org/nanodot/?p=4813

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

Another group working on machinery to produce tissue engineered blood vessels: "German researchers have been working at growing tissue and organs in the laboratory for a long time. These days, tissue engineering enables us to build artificial tissue, although science has still not been successful with larger organs. Now researchers at the Fraunhofer group of applied research institutes are applying new techniques and materials to come up with artificial blood vessels in their BioRap project that will be able to supply artificial tissue and, perhaps, even complex organs in the future. ... The aim of tissue engineering is to create organs in the laboratory for opening up new opportunities in the field. Unfortunately, researchers have still not been able to supply artificial tissue with nutrients because they do not have the necessary vascular system. Five Fraunhofer institutes joined forces in 2009 to come up with biocompatible artificial blood vessels. It seemed impossible to build structures such as capillary vessels that are so small and complex and it was especially the branches and spaces that made life difficult for the researchers. But production engineering came to the rescue because rapid prototyping makes it possible to build workpieces in line with any complex three-dimensional (3D) model. Now scientists at Fraunhofer are working on transferring this technology to the generation of tiny biomaterial structures by combining two different techniques: 3D printing technology established in rapid protoyping and multiphoton polymerisation developed in polymer science."

Link: http://www.engineeringnews.co.za/article/when-ink-becomes-an-artificial-vessel-system-2011-10-21

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

Researchers investigating calorie restriction have noticed that its effects on longevity can be inherited through epigenetic variations - which makes sense, given the reasons why individual longevity variations in response to available food evolved in the first place. If it is advantageous for a given individual at a given time to shift metabolism into a mode that allows it to live longer due to a decline in available food, then it's probably also advantageous for the children to do that from birth as well: "The tiny soil-dwelling worms C. elegans, when given mutations that make them live longer, transmit that trait even when their progeny don't inherit the life-extending mutations. ... Although much more research remains to be done, the new study raises the tantalizing possibility that if Grandma practiced caloric restriction - which affects the expression of longevity-enhancing genes - her descendants might reap the benefits. The inheritance occurs through "epigenetics": alterations not in the coding sequence of DNA (those ubiquitous A's, T's, C's, and G's) but in chemical changes that affect whether genes are expressed. ... [A] protein complex called ASH-2 [alters] histones in C. elegans, reconfiguring the histone-DNA complex into an 'open' state that promotes gene expression. Deficiencies in ASH-2 extend the worm's life span by as much as 30 percent. ... [researchers] blocked the three key proteins that make up the ASH-2 complex by mutating their genes. As expected, the worms lived longer - typically, an extra seven days beyond their lab life span of 20. [Researchers] bred the mutated worms with normal worms until their descendants no longer had the mutations. Nevertheless, the progeny still lived longer, as did their own descendants: even though their genes for the key proteins were normal, an epigenetic memory of longevity persisted."

Link: http://www.technologyreview.com/biomedicine/38943/

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