An open access commentary: "Aging is now viewed as a plastic phenotype that can be altered by nutritional, pharmacological and genetic manipulations. However, most pro-longevity mutations are discovered by systematic gene deletion or RNA interference screens, which mainly reveal abolished or diminished gene functions. In our recent publications, we used global acetylation proteome screens to study aging in yeast, and showed that enhancing the function of certain genes through specific acetylation can promote longevity. ... It is well known that acetylation of histone proteins in cultured human fibroblasts decreases during aging, which is believed to be directly related to decreased metabolic rate and reproductive capacity associated with aging. However, histone deacetylation is not likely to be a universal driving force of aging because histone acetylation and deacetylation mimetics similarly shortened life span, which could simply reflect nonspecific fitness decreases in both instances. Extension of lifespan promoted by certain genetic and/or pharmacological perturbations will more likely lead to identification of bona fide regulatory factors of aging. ... Aging is conventionally thought to be characterized by accumulation of molecular, cellular, and organ damage, leading to increased vulnerability to disease and death. Our data, on the contrary, support the idea that the gradual loss of a crucial component promoting 'healthy young status' might underlie an intrinsic aging process. Many of the mutations that extend life span decrease the activity of external nutrient signaling, such as the IGF (insulin-like growth factor)/insulin and the TOR (target of rapamycin) pathways, suggesting that they may induce a metabolic state similar to that resulting from periods of food shortage."

Link: http://impactaging.com/papers/v3/n10/full/100398.html

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

Loss of the p66(Shc) gene is a canonical example of the rampant complexity of metabolism when it comes to determinants of longevity. If you look back in the Fight Aging! archives, you'll see what I mean: years of work on p66(Shc) mutant mice that piles higher with each new paper, an accumulation of mechanisms, alterations, chains of cause and effect, altered feedback loops, and so forth - all spawned from knocking out this one gene.

It is the height of optimistic hubris to suppose that we'll be safely tinkering with human metabolism in the same way any time soon - which is one of the reasons why efforts to merely slow aging are the slow boat to China. The fast path is to work on ways to repair our existing metabolism; don't change it, just find methods to put it back the way it was when we were young. A great deal more is known about how to go about reversing aging than is known about how to slow aging.

But I digress, as I really did want to talk about p66(Shc). In addition to being a poster child for the complexities of metabolism and genetic determinants of longevity, this gene also turns out to be a good example to draw upon when explaining why it is that there are so many small genetic tweaks capable of extending life in mice. Why didn't evolution select for these small modifications in the first place? See this paper for a starting point:

Deletion of the p66(Shc) gene results in lean and healthy mice, retards aging and protects from aging-associated diseases, raising the question of why p66(Shc) has been selected, and what is its physiological role. We have investigated survival and reproduction of p66(Shc) -/- mice in a population living in a large outdoor enclosure for a year, subjected to food competition and exposed to winter temperatures. Under these conditions deletion of p66(Shc) was strongly counterselected. Laboratory studies revealed that p66(Shc) -/- mice have defects in fat accumulation, thermoregulation and reproduction, suggesting that p66(Shc) has been evolutionarily selected because of its role in energy metabolism. These findings imply that the health impact of targeting aging genes might depend on the specific energetic niche and caution should be exercised against premature conclusions regarding gene functions that have only been observed in protected laboratory conditions.

So in other words, lack of p66(Shc) only extends life and causes the mutants to prosper as individuals if they have the benefits of civilization and technology: secure food supplies, secure heating, protection from the elements, and so forth. If shoved out into the uncaring world, they fare poorly - and would soon enough vanish as a genetic line, out-competed by animals with shorter life spans but a better adapted metabolism. We might expect to see similar results for the range of other longevity genes discovered in small mammals: if there was an evolutionary benefit to their selection for animals in the wild, then we should expect that these longevity mutations would already have been selected.

Is this result anything other than just interesting for those of us following along at home? Well, it might help to further inform out thinking as to the odds of significant human longevity mutations - which I suspect are low, by the way, though I do think there will be many minor longevity genes found in humans, with very limited effects. We are already unusually long-lived for primates, and primates are long-lived in comparison to other similarly sized mammals, and that seems to have squeezed down the range of life span differences that can be created through metabolic tinkering - or at least this is currently the consensus based on what is known of the effects of calorie restriction on metabolism and health in humans.

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

Teeth are one of the first parts of our body to become seriously damaged as the years go by, thanks to bacterial agents, but that will soon enough be a thing of the past. On the one hand enamel regeneration is close to realization, and on the other hand so are ways of eliminating the agents of tooth decay: "A new mouthwash developed by a microbiologist at the UCLA School of Dentistry is highly successful in targeting the harmful Streptococcus mutans bacteria that is the principal cause tooth decay and cavities. In a recent clinical study, 12 subjects who rinsed just one time with the experimental mouthwash experienced a nearly complete elimination of the S. mutans bacteria over the entire four-day testing period. ... This new mouthwash is the product of nearly a decade of research conducted by Wenyuan Shi ... Shi developed a new antimicrobial technology called STAMP (specifically targeted anti-microbial peptides) [which] acts as a sort of 'smart bomb,' eliminating only the harmful bacteria and remaining effective for an extended period. ... With this new antimicrobial technology, we have the prospect of actually wiping out tooth decay in our lifetime."

Link: http://www.sciencedaily.com/releases/2011/11/111116045657.htm

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

From h+ Magazine: "As serious life extension appears on an ever nearer horizon simultaneous with a period of social and economic rebellion and an increasing sense of global chaos, this may be a good time to entertain these anxieties while thinking beyond the two extant competing simplistic arguments. The current conflicting views seem to be these: A: Hyperlongevity will be for rich people only and we can't afford to add to the population vs. B: Technologies get distributed to more and more people at an increasing rate of speed through the auspices of the free market. Demand increases. Production increases. The price gets lower. Demand increases. Production increases. The price gets lower... ad infinitum. In fact, the wealthy who are the early adopters of a new technology get to spend a lot of money on crappy versions of new technologies that are not ready for prime time. At the risk of being obvious, it seems like there's a lot of room in the middle for more nuanced, less certain views. ... Very few people would say that we shouldn't cure cancer or heart disease because only the wealthy will be able to afford it - and those who did would be seen by most as anti-human and/or insufferably whiny. Seen in this light, it becomes obvious that this whole 'only the rich will get hyperlongevity' mentality is pathetic in the extreme - a concession of defeat before the outset. If you think optimal health and longevity should be distributed, you won't say, 'Well, it won't be distributed so I'm against it.' You will try to make sure it gets distributed. Whether you believe in medical care for all through government or pushing these solutions towards a very large mass market or creating an open source culture that takes production and distribution into its own decentralized hands, you'll work or fight for one or several (or all) of these solutions."

Link: http://hplusmagazine.com/2011/11/15/live-long-and-prosper-umm-well-get-back-to-you-on-that-prosper-bit/

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

Here is an interesting application of cell therapy, which demonstrates the point that an artificial replacement for an organ doesn't necessarily have to replicate the form and structure of that organ: "Eight-month-old Iyaad Syed now looks the picture of health - but six months ago he was close to death. A virus had damaged his liver causing it to fail. Instead of going on a waiting list for a transplant, doctors injected donor liver cells into his abdomen. These processed toxins and produced vital proteins - acting rather like a temporary liver. The cells were coated with a chemical found in algae which prevented them from being attacked by the immune system. After two weeks his own liver had begun to recover. ... The question now is whether the technique could be used to benefit other patients with acute liver failure. The team [is] urging caution - a large clinical trial is needed to test the effectiveness of the technique. ... The principle of this new technique is certainly ground-breaking and we would welcome the results of further clinical trials to see if it could become a standard treatment for both adults and children."

Link: http://www.bbc.co.uk/news/health-15744176

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

As knowledge of cellular programming and signaling systems increases, the future of cell therapies will most likely move away from transplants and towards controlling existing populations of cells in the body: "In order to regenerate damaged heart muscle as caused by a heart attack [simpler] vertebrates like the salamander adopt a strategy whereby surviving healthy heart muscle cells regress into an embryonic state. This process, which is known as dedifferentiation, produces cells which contain a series of stem cell markers and re-attain their cell division activity. Thus, new cells are produced which convert, in turn, into heart muscle cells. The cardiac function is then restored through the remodelling of the muscle tissue. An optimised repair mechanism of this kind does not exist in humans. Although heart stem cells were discovered some time ago, exactly how and to what extent they play a role in cardiac repair is a matter of dispute. It has only been known for a few years that processes comparable to those found in the salamander even exist in mammals. ... [Researchers have] now discovered the molecule responsible for controlling this dedifferentiation of heart muscle cells in mammals. The scientists initially noticed the high concentration of oncostatin M in tissue samples from the hearts of patients suffering from myocardial infarction. It was already known that this protein is responsible for the dedifferentiation of different cell types, among other things. ... Using a mouse infarct model, the [researchers] succeeded in demonstrating that oncostatin M actually does stimulate the repair of damaged heart muscle tissue as presumed. One of the two test groups had been modified genetically in advance to ensure that the oncostatin M could not have any effect in these animals. ... The difference between the two groups was astonishing. Whereas in the group in which oncostatin M could take effect almost all animals were still alive after four weeks, 40 percent of the genetically modified mice had died from the effects of the infarction."

Link: http://www.sciencedaily.com/releases/2011/11/111111095220.htm

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

A reminder: "Biological aging is the greatest health threat to humanity today. It causes more disease and suffering in the world than all infectious diseases (HIV, malaria, etc.) or any other cause (e.g. poverty, war, natural disaster, etc.). The inborn aging process causes cancer, heart disease, stroke, AD, joint pain, vision and hearing impairment, etc. The harms of senescence (even if we exercise and eat a healthy diet) are certain, severe and universal. The diseases of aging afflict both rich and poor, and developed and developing countries. And, unless the biological clocks we have inherited from our Darwinian past are modified, it is highly likely that all future generations of human beings that shall ever live on this planet will suffer one or more of the diseases of aging. In light of the unique health challenges facing the world's aging populations, the most important knowledge humans can acquire today is knowledge about the biology of aging: why do we, as a species, age at the rate we do? why does aging leave our bodies and minds susceptible to disease? And, most importantly, how can we retard or ameliorate the harmful effects of biological aging?"

Link: http://colinfarrelly.blogspot.com/2011/04/time-waits-for-no-one.html

Via EurekAlert!: "Researchers for the first time have induced robust regeneration of nerve connections that control voluntary movement after spinal cord injury, showing the potential for new therapeutic approaches to paralysis and other motor function impairments. ... They did this by deleting an enzyme called PTEN (a phosphatase and tensin homolog), which controls a molecular pathway called mTOR that is a key regulator of cell growth. PTEN activity is low early during development, allowing cell proliferation. PTEN then turns on when growth is completed, inhibiting mTOR and precluding any ability to regenerate. ... Until now, such robust nerve regeneration has been impossible in the spinal cord. ... An injury the size of a grape can lead to complete loss of function below the level of injury. For example, an injury to the neck can cause paralysis of arms and legs ... These devastating consequences occur even though the spinal cord below the level of injury is intact. All these lost functions could be restored if we could find a way to regenerate the connections that were damaged. ... are now studying whether the PTEN-deletion treatment leads to actual restoration of motor function in mice with spinal cord injury."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-08/uoc--ibn080510.php

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

A Science 2.0 article looks at the work of researcher Michael Rose over past decades: "Over the years, Rose and his lab have bred fruit flies to live four times the life span of an average fruit fly. Reasoning from those studies, Rose has proposed that, because the life spans of fruit flies have the genetic capability to be extensively prolonged, human life can be manipulated in the same way. ... Wattiaux was a French scientist working at the University of Leuven in Belgium. His study used the same fruit flies that Rose had been working with ... Wattiaux found that when he made each new generation of fruit flies that were the offspring of old parents exclusively, the flies showed an increased life span after each generation. But Wattiaux didn't know why his fruit flies lived longer. He felt that longevity increased because of a nongenetic effect, but he didn't have any direct evidence. Rose did. Wattiaux's results, he saw, showed the importance of the force of natural selection. He believed that, because natural selection stops working at a late age and fails to eliminate genes with detrimental effects, these bad genes would not be removed by natural selection. Instead, they would accumulate. In populations that reproduce early, natural selection declines early. Alternatively, populations that are old when they reproduce will continue to be subject to powerful selection until they begin to reproduce. Thus, by allowing older flies to reproduce over generations, natural selection would continue to choose the flies that are able to breed at a later age - the fittest flies."

Link: http://www.science20.com/forever_fly/forever_fly_forever_diet-78126

Advanced glycation end-products (AGEs) seem to be important in aging, their buildup effectively a form of damage that harms cellular processes in a number of ways. Here, researchers suggest that an AGE precursor chemical is also problematic: "Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases."

View the Article Under Discussion: http://pmid.us/20393592

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

Researchers here demonstrate that comparatively simple stem cell transplants may be effective in regenerating lung injuries: "Human stem cells administered intravenously can restore alveolar epithelial tissue to a normal function in a novel ex vivo perfused human lung after E. coli endotoxin-induced acute lung injury (ALI) ... ALI is a common cause of respiratory failure in the intensive care units, often leading to death. It can be caused by both direct injury such as aspiration and pneumonia, and indirect injury such as sepsis and from trauma. ... Yearly, ALI affects approximately 200,000 patients in the US and has a 40 percent mortality rate despite extensive investigations into its causes and pathophysiology. Innovative therapies are desperately needed. ... we found that intravenous infusion of [stem cells] preferentially homed to the injured areas of the lung, which means that the cells find their way from the bloodstream to the sites in the lung of injury. ... In addition to having restored function of alveolar epithelial cells, lungs treated with [stem cells] showed a reduction in inflammatory [cytokine] levels suggesting a favorable shift away from a proinflammatory environment in the injured alveolus."

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/ats-scr051010.php

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

Another step forward for tissue engineers: "scientists have created an eight-layer, early stage retina from human embryonic stem cells, the first step toward the development of transplant-ready retinas to treat eye disorders such as retinitis pigmentosa and macular degeneration that affect millions. ... The retina is the inside back layer of the eye that records the images a person sees and sends them via the optic nerve from the eye to the brain. Retinal diseases are particularly damaging to sight. More than 10 million Americans suffer from macular degeneration, the leading cause of blindness in people over 55. About 100,000 have retinitis pigmentosa, a progressive, genetic disorder that usually manifests in childhood. ... To mimic early stage retinal development, the researchers needed to build microscopic gradients for solutions in which to bathe the stem cells to initiate specific differentiation paths. ... creating transplantable retinas from stem cells could help millions of people, and we are well on the way. ... researchers are testing the early-stage retinas in animal models to learn how much they improve vision. Positive results would lead to human clinical trials."

View the Article Under Discussion: http://today.uci.edu/news/2010/05/nr_retina_100526.php

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

From CBC News: "Scientists in Toronto are trying to crack the secrets of regeneration to trigger the human body to grow tissues and organs damaged by disease. In his lab at Mount Sinai Hospital, Dr. Ian Rogers is working on a replacement pancreas that would be grown in a lab and then placed in those with Type 1 diabetes to restore their insulin production. ... At this stage, Rogers's team is building a pancreas out of a surgical sponge, a three-dimensional structure seeded with insulin-producing islet cells. The pancreas would be grown in the lab and then placed under the skin of those with Type 1 diabetes to restore their insulin production. But making a pancreas is complicated, Rogers said. The most advanced research at his lab is simpler: regenerating blood vessels so people with Type 2 - or adult onset - diabetes who have damaged fingers and toes can avoid amputation. In theory, any condition where cells are damaged - from insulin-producing cells in diabetes to brain cells in Alzheimer's and Parkinson's disease, to retina cells in blindness, to damaged areas in the heart - could one day be repaired. ... If we can find a way to replace these cells back in to where it's missing, we can envision a cure for these diseases which are currently devastating."

View the Article Under Discussion: http://www.cbc.ca/health/story/2010/07/20/regenerative-medicine-toronto.html

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

Connections make the world go round - networking and relationships, if you like: establishing and maintaining them. This is just as true of companies and their employees and customers as it is of any collection of people. A company that manages relationships well is a company that will prosper. This is actually surprisingly hard, however, even with resolve and the best of intentions from all parties, as anyone who has been on the inside of that part of business life will attest to.

On this topic, I see that cryonics provider Alcor, under the guidance of CEO Max More, is making an effort to make its operations far more transparent and in the process improve relationships with both its members and the broader community of people interested in cryonics - a source of future supporters and growth for the business. So, for example, you see regular sets of posts reporting on operations, intentions, research, and other progress such as these at the Alcor blog:

CEO Report

The never-ending quest for cost reductions continues. A review of Alcor's utility bills and an examination of the roof space made it clear that thousands of dollars per year have been avoidably incurred in the form of unnecessarily high air conditioning bills. We have asked for bids from three companies and will choose one in the coming week to improve insulation and install radiant barriers. Judging by the remarkable escalation in billing during the hotter months (in some units of the building more than others), the annual savings should make this investment pay off in a pleasingly short time.

...

On the communications front, Barry Aarons is helping us deploy the Alcor Speakers' Bureau to give talks to organizations in the area. A few weeks ago, we started this effort modestly with me giving a talk to the Midtown Lion's Club. The goal is to build a reputation and have a voice in the influential local business groups.

Readiness and Transport Report

An Alcor member in the New York area was placed on a ventilator following a recent serious medical event. Catherine Baldwin of Suspended Animation (SA) traveled to the area to establish a relationship with the medical facility and mortuary in the event stabilization was needed. Although the member's health has temporarily improved it was decided that a full standby was not warranted, she continues to struggle with her illness and may eventually need our services.

Research and Development

Based on our findings last month that the mylar cooldown blanket significantly reduced the LN2 usage of our automated perfusion and cooldown table with an empty patient pod, Steve Graber decided to conduct a more rigorous cooldown test utilizing four 20L water bladders in the pod cavity and a target cooling temperature of -80C.

If you look at the recent administrative report, you'll find a link to the membership and cryopreservation counts in graphical form for the last forty years - which is food for thought:

As of October 31, 2011, Alcor has 951 members and 108 patients.

In the grand scheme of things, cryonics has yet to climb into the big leagues. The potential is there, and much like the potential for rejuvenation biotechnology, there are great challenges inherent in trying to convince people to see it and believe it. "Why isn't cryonics a multi-billion dollar international industry?" is one of those questions like "Why don't more people wholeheartedly support research into reversing human aging?" - we can talk around the issue a great deal, but there are few firm answers at the end of the day. If we knew definitively where the point of failure was in persuasion and desire, why exactly the urge to spend money on the expectation of more life, so very much in evidence elsewhere, peters out for cryonics and longevity science, then we'd be working on fixing that problem as opposed to working on the various problems and challenges we only believe to be significant.

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

The Institute for Evidence Based Cryonics is hosting a symposium in Portland in July:

On Saturday July 7, 2012, the Institute for Evidence Based Cryonics and Cryonics Northwest will organize a symposium on cryonics and brain-threatening disorders in Portland, Oregon. The symposium will start at 09:00 am at the offices of Kaos Softwear. Entrance to the event is free.

Some background is provided in another post at the Institute website:

Conventional wisdom in life extension circles is that making cryonics arrangements allows one to benefit from rejuvenation technologies that are not available during one's existing lifespan. Aside from the risk of high-impact accidents or getting lost at sea, there is one challenge that some cryonicists will face when they grow older; the debilitating consequences of brain-threatening disorders.

One of the unfortunate effects of the increase in human lifespan is a corresponding increase in late-onset identity-destroying brain disorders. We know that some patients at the existing cryonics organizations were cryopreserved after advanced Alzheimer's disease. Some cryonics organization members who developed Alzheimer's disease were not preserved at all, due to lapsed insurance and/or cryopreservation arrangements.

The main challenges and risks associated with low-temperature preservation of the brain after death relate to (a) overbearing regulation that prevents sensible end of life decisions and increases risk of a poor preservation, and (b) your removal from the scene as a willful actor, capable of defending your own interests. Neurodegenerative conditions like Alzheimer's are a special case of point (b) - you are still alive, but become incapable of monitoring affairs to ensure that the course of action you desire is carried out.

All the data of your mind may still be largely intact, as appears to be the case for Alzheimer's until late in its progression, or it may be progressively and irrevocably destroyed by a disease that will have largely consumed you by the time it kills your body. Either way, a lot of entirely disreputable things happen behind closed doors when family members are close to death and cannot look out for themselves - I'm sure we can all recall a tale or two. Which is all fine and well if it's just an inheritance fight, but when it means the difference between your brain and the data of your mind preserved well at Alcor or rotting away to guaranteed oblivion ... well, that's a much bigger deal.

These are challenges, given that the best we can do today is to try change the laws that prevent voluntary euthanasia, support research into biotechnologies that can repair the brain, and live an exceedingly healthy life. Many of these issues relating to the brain and cryopreservation could be dealt with if Western governments didn't force people to live to the bitter end, no matter the personal cost. On the general health side of things, it is true that fit older folk don't tend to suffer Alzheimer's, which appears to be just as much a lifestyle disease as type 2 diabetes for most people. There are still any number of other degenerations, however, and even the best kept body and brain deteriorate progressively until death.

So, as people tend to point out, support of cryonics is not a complete alternative to support of medical biotechnology - people who will not live to see the advent of true rejuvenation biotechnologies should still be very interested in medical progress in regenerative medicine and other fields likely to support therapies and methods of preventation for the degeneration of the brain with aging.

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

The FDA seems to be succeeding in the courts with regard to shutting down the few groups in the US trying to offer first generation stem cell therapies, and placing a heavy burden of regulation upon them. This most likely means that for another decade or so the only realistic way to access most of the present variety of stem cell therapies will continue to be medical tourism: "It's official: stem cells are drugs. At least, that's the opinion of the US district court in Washington DC, which has ruled that the Food and Drug Administration (FDA) has the authority to regulate clinics offering controversial stem cell therapies. Treatments in which stem cells are harvested from bone marrow and injected straight back into the same patient are deemed part of routine medical practice - not regulated by the US government. But if the cells are subjected to more than 'minimal manipulation', the FDA maintains that the therapy becomes a 'drug', which must be specifically approved for use. It was on this basis that in 2008 the FDA began moves to shut down Regenerative Sciences, a clinic in Broomfield, Colorado, that treats orthopaedic problems using a stem cell therapy called Regenexx. ... Regenexx consists of mesenchymal stem cells, which give rise to tissues including bone and cartilage, taken from a patient's bone marrow and grown in culture for about two weeks. Centeno has published a series of case reports describing its use to treat joint problems - but no controlled clinical trials. ... Regenerative Sciences challenged the FDA's authority to regulate its activities, setting the stage for a legal fight. In 2010, the FDA sought an injunction to take Regenexx off the market. This has now been granted in the court's ruling. Christopher Centeno, medical director of Regenerative Sciences, vows to appeal. 'This is really round one. Our position remains that a patient's cells are not drugs.'"

Link: http://www.newscientist.com/blogs/shortsharpscience/2012/07/ruling-frees-fda-to-crack-down.html

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

You may recall that an Italian group has been engineering and transplanting comparatively simple organ structures - such as tracheas - in recent years. The researchers have used a range of techniques to build these organs from the patient's own cells, such as decellularization and nanoscale polymer scaffolds. The former requires a donor organ to be stripped of cells in order to provide a scaffold formed of its extracellular matrix, while the latter results in a completely synthetic organ. In both cases, the raw materials that form that scaffold are populated with the patient's own cells, leading to a transplant without the risk of immune rejection.

This is all very promising groundwork for later and more extensive tissue engineering of replacement parts to order. The first synthetic trachea transplant occurred earlier this year, and an update is doing the rounds:

The Eritrean patient, 36-year-old Andemariam Teklesenbet Beyene, was the first person in the world to receive this type of transplant in June, 2011 at the Karolinska University Hospital, Stockholm, Sweden. ... Currently Beyene is living in Reykjavík, Iceland, where he is a geology student studying for his PhD. Beyene's wife and two children live in Eritrea. ... The patient has been doing great for the last 4 months and has been able to live a normal life. After arriving in Iceland at the start of July, he was 1 month in hospital and another month in the rehabilitation center. Already at the rehabilitation center he could start to work on his Master of Science Thesis in Geophysics, a scientific project that he has been working on for the last years at the University of Iceland here in Reyklavik. For the last two months he has been able to focus on his studies and the plan is the he will defend his thesis at the end of this year.

...

A 30-year-old man from Maryland, USA, who also had primary cancer of the airway, is the second patient to receive a bioartificial scaffold transplantation from Prof. Macchiarini. The scaffold used in this case was created from nanofibres and therefore, according to Prof. Macchiarini, represents a further advance from the transplant Beyene received. Prof. Macchiarini's team is now hoping to use the same technique in order to treat a 13-month old South Korean infant.

...

We will continue to improve the regenerative medicine approaches for transplanting the windpipe and extend it to the lungs, heart, and oesophagus. And investigate whether cell therapy could be applied to irreversible diseases of the major airways and lungs.

So good news all round so far - this is one of the more successful lines of work in tissue engineering, and with success so clearly demonstrated you can be certain that other clinics worldwide will adopt these techniques over the next few years.

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

We are our brains, and so there isn't much room for outright replacement with new tissue as a strategy for regeneration anywhere inside the skull. Thus it is very important that researchers develop ways to repair the brain in situ. Fortunately, it looks as though this goal will be achievable sooner rather than later, with comparatively early stage stem cell therapies: "Neuron transplants have repaired brain circuitry and substantially normalized function in mice with a brain disorder, an advance indicating that key areas of the mammalian brain are more reparable than was widely believed. ... [Researchers] transplanted normally functioning embryonic neurons at a carefully selected stage of their development into the hypothalamus of mice unable to respond to leptin, a hormone that regulates metabolism and controls body weight. These mutant mice usually become morbidly obese, but the neuron transplants repaired defective brain circuits, enabling them to respond to leptin and thus experience substantially less weight gain. Repair at the cellular-level of the hypothalamus - a critical and complex region of the brain that regulates phenomena such as hunger, metabolism, body temperature, and basic behaviors such as sex and aggression - indicates the possibility of new therapeutic approaches to even higher level conditions such as spinal cord injury, autism, epilepsy, ALS (Lou Gehrig's disease), Parkinson's disease, and Huntington's disease. ... There are only two areas of the brain that are known to normally undergo ongoing large-scale neuronal replacement during adulthood on a cellular level - so-called 'neurogenesis,' or the birth of new neurons - the olfactory bulb and the subregion of the hippocampus called the dentate gyrus, with emerging evidence of lower level ongoing neurogenesis in the hypothalamus. The neurons that are added during adulthood in both regions are generally smallish and are thought to act a bit like volume controls over specific signaling. Here we've rewired a high-level system of brain circuitry that does not naturally experience neurogenesis, and this restored substantially normal function."

Link: http://www.eurekalert.org/pub_releases/2011-11/hms-rtb112311.php

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

There have been a number of research results in the past year or two that suggest the barriers posed by age to the production of patient-specific cells suitable for stem cell therapies are lower than first thought. Several research groups have obtained useful cells from old patients, showing that age-related damage to patient cells is no barrier to reprogramming them - indeed, the reprogramming appears to repair many types of damage. Here is another such result: "Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs) acquire features of human embryonic stem cells (hESCs) and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. ... Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the [potential of reprogrammed cells to spawn cancer] due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. ... Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. ... all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence of genomic alterations."

Link: http://dx.doi.org/10.1371/journal.pone.0027352

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

A PDF document that I think you'll find interesting: "Reports on the latest research of what makes us unhealthy, or what could make us live longer, are common from magazines, newspapers and websites. Often, the messages get shortened so that it sounds like one risk factor dominates. The reality is that the way in which many relevant risk factors work together is still not yet fully understood, and there is an element of chance affecting the longevity prospects of each of us. ... the overarching context is consistent improvement in longevity worldwide. Life expectancy has only ever declined in a few countries subject to specific and significant negative mortality risk. While we need to examine the trees of individual risk factors, there is much to be said for pausing to look at the woods of the consistent achievement in longevity progress. Longevity Bulletin aims to provide a regular guide to the prospects for long lives. It presents and explains actuarial perspectives on population longevity and looks outside the profession for statistics, research and the latest thinking on related subjects. It is not intended as a comprehensive guide to everything new in longevity research but rather as a helpful companion for those interested in a most intriguing subject."

Link: http://www.actuaries.org.uk/research-and-resources/pages/longevity-bulletin

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