Decellularization involves taking a donor organ and stripping its cells, leaving just the shaped extracellular matrix behind. When new cells of the right types are seeded into the matrix, they will inhabit it, grow, and follow its cues to rebuild the tissue as it was. This might prove to be a shortcut to the future of organs grown to order - you can't use it to produce an organ such as the heart from scratch, but you can take animal organs and make it possible to transplant them into humans with minimal risk of rejection.

This, at least, is the goal. So far decellularization has worked for some human donor tissues, such as veins, replacing the donor's cells with those of the recipient to remove immune rejection issues. This suggests that it will work just fine for animal organs too. Researchers are working on opening the doors to widespread xenotransplantation of pig organs, for example, by turning porcine tissues into those of the organ recipient.

Saving lives with help from pigs and cells

One recent morning, a pig heart hung suspended in a clear homemade tank in the lab built for Taylor and her team. Filled with detergent, the heart had expanded to the size of a large man's fist, excess liquid dripping slowly out its sides.

Once the heart is thoroughly cleaned, hard-working human stem cells - immature cells found in our organs and tissues that help repair damage on a daily basis - will bring it to life. "We can take stems cells from bone marrow, blood or fat and place them onto a heart, liver or lung scaffold," Taylor explains. "My motto for a long time has been 'Give nature the tools and get out of the way.'?"

Taylor and her team will add stem cells to the heart one of two ways: by inserting a tube in the aorta and letting the cells drip inside, or by injecting the cells with a syringe through the wall of the heart. A heartbeat is perceptible after just a few days. Within a few weeks, the heart is strong enough to pump blood.

Taylor predicts that in the next two years, she and her team will approach the U.S. Food and Drug Administration and ask to do a first-in-human study with the bio-artificial hearts. "Will it be a whole heart? Probably not," Taylor says. "But it could be a cardiac patch or a valve. We might start with a piece to show the safety and efficacy of the technology."

Source:
http://www.fightaging.org/archives/2013/02/working-on-the-use-decellularization-to-make-pig-hearts-suitable-for-human-transplantation.php

From a few weeks back, an audio interview with Aubrey de Grey of the SENS Research Foundation:

Anti-aging scientist and biogerontologist Aubrey de Grey told [the host] about his work with the SENS Foundation, an organization he founded with the purpose of defeating aging. According to him, aging is treated as a disease that should be defeated by targeting the 7 cellular activities that cause us to age. Dr. de Grey discussed the science that researchers at SENS are studying to back up the claim that we could live to 1000 years some day soon. "The problem is the funding," de Grey said. "We've been trying to fight what we've described as the pro-aging trance." The pro-aging trance, according to Dr. de Grey, is the social conception we have that death is inevitable. "No one wants to keep cancer, no one wants to keep heart disease, so what would we want to keep aging?" de Grey asks. Part of Aubrey de Grey's work is marketing his ideas and helping to diminish the acceptance society has of death. Citing his long beard which [the interviewer] said looked "like Rasputin's," de Grey said, "This is something my team and I have discussed. It's something that helps me stick in people's minds."

[The interviewers] briefly talked about the social, economic, and cultural consequences of a longer life extension. When [the interviewers] pressed de Grey on these issues, Aubrey reiterated that his work is not a "longevity issue, but a health care issue, so stop thinking of it that way please." Aubrey pressed that the key for his scientific success lies in his publicity: getting more exposure and raising money through his foundation.

Link: http://glucksolutions.podomatic.com/entry/index/2013-01-18T12_39_16-08_00

Source:
http://www.fightaging.org/archives/2013/02/a-podcast-interview-with-aubrey-de-grey.php

Here is another small step on the way towards the creation of artificial cells as medical devices. If you can wrap nanoparticles in cell membranes, then its not hard to see that disguising any arbitrary nanomachinery that way is on the agenda - such as those that can dispense or create proteins, or perform other tasks inside our tissues.

By cloaking nanoparticles in the membranes of white blood cells, [scientists] may have found a way to prevent the body from recognizing and destroying them before they deliver their drug payloads. "Our goal was to make a particle that is camouflaged within our bodies and escapes the surveillance of the immune system to reach its target undiscovered. We accomplished this with the lipids and proteins present on the membrane of the very same cells of the immune system. We transferred the cell membranes to the surfaces of the particles and the result is that the body now recognizes these particles as its own and does not readily remove them."

Nanoparticles can deliver different types of drugs to specific cell types, for example, chemotherapy to cancer cells. But for all the benefits they offer and to get to where they need to go and deliver the needed drug, nanoparticles must somehow evade the body's immune system that recognizes them as intruders. The ability of the body's defenses to destroy nanoparticles is a major barrier to the use of nanotechnology in medicine. Systemically administered nanoparticles are captured and removed from the body within few minutes. With the membrane coating, they can survive for hours unharmed.

"Being able to use synthetic membranes or artificially-created membrane is definitely something we are planning for the future. But for now, using our white blood cells is the most effective approach because they provide a finished product. The proteins that give us the greatest advantages are already within the membrane and we can use it as-is."

Link: http://www.sciencedaily.com/releases/2013/01/130131144114.htm

Source:
http://www.fightaging.org/archives/2013/02/wrapping-nanoparticles-in-cell-membranes.php

One of the side-effects resulting from members of the research community now being far more willing to talk openly about engineering human longevity or building therapies for aging is that university publicity offices are now far more willing to write materials that sound like something the "anti-aging" market would come up with. That's not great, but it is what it is - as for the mass media and marketing, the primary incentives for these folk have nothing to do with truth, accuracy, or helping the public understand the actual relevance of a particular research result. If any of those things happen, it's either by accident or because they help achieve the real goals of the publicity group. Bear that in mind while reading the release materials linked below.

Sirtuins have been a hot topic in aging research - largely undeservedly as it turned out - for some years, the large sums of money flowing into that field of research helping to drive enthusiasm for the slow, expensive road of slowing aging by metabolic manipulation. Most of the relevant research community, those who might be working on SENS or other rejuvenation biotechnologies if the money was there, work towards similar goals. They are producing knowledge rather than applications that can influence human lifespan, and have little expectation of producing anything more than knowledge for decades to come. Knowledge is never useless, but this path is not likely to deliver meaningful extension of human life in time to matter to us, nor is it likely to produce technologies that will help people who are already aged.

There are a number of different sirtuins, and while research initially focused on SIRT1, it is SIRT3 and SIRT6 that have generated the more interesting results in the past couple of years. SIRT3 is the topic for today, a mitochondrial protein - it is noteworthy to see just how many longevity-related genes and proteins are connected to the mitochondria in some way. Calorie restriction is noted to boost levels of SIRT3, and SIRT3 is thought to promote antioxidant activity in cells, reducing damage in the places where oxidants are produced as a side-effect of the operation of metabolism - something that you can't achieve by ingesting antioxidants, I should add.

Here, researchers demonstrate a modest reversal of one small aspect of the breadth of aging biology by boosting levels of SIRT3 in old mice:

Discovery opens the door to a potential 'molecular fountain of youth'

The researchers first observed the blood system of mice that had the gene for SIRT3 disabled. Surprisingly, among young mice, the absence of SIRT3 made no difference. It was only when time crept up on the mice that things changed. By the ripe old age of two, the SIRT3-deficient mice had significantly fewer blood stem cells and decreased ability to regenerate new blood cells compared with regular mice of the same age.

What is behind the age gap? It appears that in young cells, the blood stem cells are functioning well and have relatively low levels of oxidative stress, which is the burden on the body that results from the harmful byproducts of metabolism. At this youthful stage, the body's normal anti-oxidant defenses can easily deal with the low stress levels, so differences in SIRT3 are less important.

"When we get older, our system doesn't work as well, and we either generate more oxidative stress or we can't remove it as well, so levels build up. Under this condition, our normal anti-oxidative system can't take care of us, so that's when we need SIRT3 to kick in to boost the anti-oxidant system. However, SIRT3 levels also drop with age, so over time, the system is overwhelmed."

To see if boosting SIRT3 levels could make a difference, the researchers increased the levels of SIRT3 in the blood stem cells of aged mice. That experiment rejuvenated the aged blood stem cells, leading to improved production of blood cells.

Source:
http://www.fightaging.org/archives/2013/01/learning-more-about-the-role-of-sirt3-in-aging.php

Vegetarianism is associated with health benefits such as reduced risk of age-related disease. It is also associated with carrying less of the visceral fat shown to cause harm to long-term health - which on balance probably means a lower calorie intake. As we all know by now, calorie intake has a disproportionate effect on measures of health. So that would seem to be a more plausible mechanism than, say, reduced dietary intake of AGEs or lower levels of methionine.

Here, however, researchers are claiming that differences in body mass index - a not-so-great proxy measure for the amount of body fat - between vegetarians and non-vegetarians are not terribly important in comparison to blood pressure and cholesterol measures. That is not a particularly intuitive result:

The risk of hospitalisation or death from heart disease is 32% lower in vegetarians than people who eat meat and fish, according to a new study. "Most of the difference in risk is probably caused by effects on cholesterol and blood pressure, and shows the important role of diet in the prevention of heart disease."

This is the largest study ever conducted in the UK comparing rates of heart disease between vegetarians and non-vegetarians. The analysis looked at almost 45,000 volunteers from England and Scotland enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% were vegetarian. Such a significant representation of vegetarians is rare in studies of this type, and allowed researchers to make more precise estimates of the relative risks between the two groups.

The Oxford researchers arrived at the figure of 32% risk reduction after accounting for factors such as age, smoking, alcohol intake, physical activity, educational level and socioeconomic background.

Participants were recruited to the study throughout the 1990s, and completed questionnaires regarding their health and lifestyle when they joined. These included detailed questions on diet and exercise as well as other factors affecting health such as smoking and alcohol consumption. Almost 20,000 participants also had their blood pressures recorded, and gave blood samples for cholesterol testing. The volunteers were tracked until 2009, during which time researchers identified 1235 cases of heart disease. This comprised 169 deaths and 1066 hospital diagnoses, identified through linkage with hospital records and death certificates.

The researchers found that vegetarians had lower blood pressures and cholesterol levels than non-vegetarians, which is thought to be the main reason behind their reduced risk of heart disease. Vegetarians typically had lower body mass indices (BMI) and fewer cases of diabetes as a result of their diets, although these were not found to significantly affect the results. If the results are adjusted to exclude the effects of BMI, vegetarians remain 28% less likely to develop heart disease.

Link: http://www.eurekalert.org/pub_releases/2013-01/uoo-vcr012913.php

Source:
http://www.fightaging.org/archives/2013/01/vegetarianism-associated-with-lower-risk-of-heart-disease.php