LONGEVITY MEME NEWSLETTER
November 8th 2010
The Longevity Meme Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to the Longevity Meme.
- Messaging Rejuvenation at the SENS Foundation
- Organs of the Future May Not Look Like Those of the Past
- The State of Stem Cell Therapy
- An Update on Early Artificial Sight
- Latest Headlines from Fight Aging!
MESSAGING REJUVENATION AT THE SENS FOUNDATION
Sarah Marr of the SENS Foundation recently explained the Foundation's positioning and present efforts to explain their mission:
"This is the basis of our core message: SENS Foundation works to advance research on rejuvenation biotechnologies. We exist because no-one else is working to deliver on the promise of rejuvenation biotechnologies, to steer academia and industry towards the adoption of a damage-repair paradigm which is currently neglected.
"The mission statement also describes these rejuvenation biotechnologies as being applied to the disabilities and diseases of aging, not simply, aging. Our approach will create a comprehensive set of interventions (on which, more later), but each of the individual interventions in that set will address one or more specific diseases, and those interventions will develop over time, not all at once. It would be wrong, therefore, to frame our mission in a way which suggested the 'all or nothing' proposition implied by our using the word aging alone. Each individual success - each new application of rejuvenation biotechnologies - will solve very real medical problems."
ORGANS OF THE FUTURE MAY NOT LOOK LIKE THOSE OF THE PAST
The evolved organs of the human body each serve a function, but their structure and mode of operation is far from the only way of getting the job done:
"Consider dialysis as a crude example that shows the function of the kidney doesn't have to be performed by a kidney, and nor does it have to be performed in the present location of the kidneys in the body. As this age of biotechnology advances, more and more people are going to purchase and make use of artificial kidneys. At the one end of the scale, you might imagine that kidney 2.0 will be a tissue engineered copy of your failing kidney 1.0 - researchers can almost build them, we know they work, and the only downside is the invasive surgery required to install a new model. But I think we will see a very wide range of kidney 2.0 products that bear as little resemblance to kidney 1.0 as does a dialysis machine.
"For example, researchers are presently developing bioartificial devices comprised of kidney cells and machinery. It doesn't take too much of a leap of imagination to see that 20 years from now, tiny permeable encapsulations of kidney cells could manufactured by the billion extremely cheaply - and injected once a week to clean the bloodstream from the inside. Alternately, a person might have a dozen implanted bioartificial dialysis machines each the size of a thumbnail sitting beside major arteries. Or kidney function could be incorporated into an implanted artificial heart while the diseased kidneys are removed entirely, and the heart machine itself is a break with the past because doesn't beat, but rather pumps blood continuously."
THE STATE OF STEM CELL THERAPY
Early stem cell therapies take the form of transplants, simply delivering a lot of stem cells and hoping for the best. Like other areas of regenerative medicine, the field is evolving rapidly.
"The high points: (a) A great deal of work is presently taking place in the field and progress is rapid. (b) Results to date have been encouraging: the benefits are more than enough to make continuing research and development worthwhile. (c) Evidence suggests that transplanted stem cells trigger healing largely through release of signaling biochemicals that spur native cells to greater efforts - rather than any other method, such as cell division to reestablish local cell populations. (d) The state of the local cellular environment is a big concern - and potentially a big influence on the success of a therapy. In the old, the dysfunctional cellular environment may cause a therapy to fail because its damaged signals outweigh those of the transplanted cells. (e) Infrastructure technologies need a great deal more work: sourcing stem cells for transplant needs to be much easier, cheaper, and more reliable.
"One intriguing view of the future is that stem cell therapies will prove to be a short-lived intermediary technology. If it is the signals that are triggering healing, then cell transplants could be done away with entirely - we only need them now because researchers do not yet understand how to reproduce the same chemical signaling that the cells deliver. This evolution might well happen over the next decade, and researchers who work with stem cells will focus instead on producing organs grown from a patient's own cells and other feats of tissue engineering."
AN UPDATE ON EARLY ARTIFICIAL SIGHT
Implanted devices that replace some of the function of specialized cells lost to degenerative blindness are advancing in their sophistication:
"Researchers based in Germany have developed a retinal implant that has allowed three blind people to see shapes and objects within days of the implant being installed. ... The device - known as a subretinal implant - sits underneath the retina, directly replacing light receptors lost in retinal degeneration. As such, it uses the eyes' natural image processing capabilities beyond the light detection stage to produce a visual perception in the patient that is stable and follows their eye movements. Other types of retinal implants - known as epiretinal implants - sit outside the retina and because they bypass the intact light-sensitive structures in the eyes they require the user to wear an external camera and processor unit. ... This seems like a natural evolution if it can be made to work in a practical fashion - cut out the aspects of the system that were awkward to manage in favor of an implant that can stand alone."
The highlights and headlines from the past week follow below.
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LATEST HEADLINES FROM FIGHT AGING!
Friday, November 5, 2010
From Singularity Hub: "Wake Forest's Institute for Regenerative Medicine (WFIRM) and the Armed Forces Institute for Regenerative Medicine (AFIRM) have developed a skin printer that can deposit cells directly onto a wound to help it heal faster. They recently presented the results of their latest experiments at the American College of Surgeons Clinical Congress (ACSCC) in Washington DC. Mice given topical wounds were able to heal in just three weeks when a new skin was printed onto the damaged area (compared to 5-6 with control groups). WFIRM and AFIRM also stated that the skin printer had been tested to see if it could print human cells, but that the next step forward would be experiments on pigs. If ultimately successful, skin printers could revolutionize the way we treat injuries - making serious wounds less fatal and rapidly speeding the healing of other injuries. ... the recent conference [gives] some valuable insights into how the skin printer actually works. Two different printing heads are used - one with skin cells, a coagulant, and collagen; the other with a different kind of coagulant. Keeping these substances separate allows them to be deposited easily (like ink) but then quickly bond together and form a solid skin covering with fibrin."
STEM CELL THERAPY FOR PERIPHERAL ARTERY DISEASE
Friday, November 5, 2010
Peripheral artery disease is one of a number of conditions shown to benefit from even early, crude efforts at stem cell transplantation: "Peripheral artery disease (PAD) affects 8 million Americans. It's when arteries in the legs narrow. The most common symptoms of PAD are cramping, pain or tiredness when walking. It can so bad that some can't walk at all. Now an experimental stem-cell therapy may offer hope to people with severe pad. Ronald Davis can move again after seven long years. 'Pain 24 hours a day, seven days a week,' said Davis. Plaque clogged the artery carrying blood to his leg, which cut off oxygen flow. ... Left alone, it can cause ulcers, gangrene and even lead to amputation. ... Davis began a last-ditch stem-cell therapy at Duke University. His leg was marked for 30 injections, totaling millions of stem cells. For him, there was no other choice. ... Cells are taken from the placentas of Israeli women who've given birth. Once injected, they secrete proteins, which boost additional cell growth. Then, it's believed those cells may contribute to the growth of additional vessels around the plaque, circumventing the blockage. ... Three days after injections, Davis was walking, and doctors say the oxygen level in his leg tissue jumped from 43 percent to 67 percent. ... This specific type of stem-cell therapy is currently involved in a Phase 1 clinical trial."
IMPROVING REPAIR AFTER A STROKE
Thursday, November 4, 2010
Some of what the body does in response to injury, especially in the nerves and brain, is in fact counterproductive in the long term: "Stroke is the leading cause of adult disability, due to the brain's limited capacity for recovery. ... Researchers interested in how the brain repairs itself already know that when the brain suffers a stroke, it becomes excitable, firing off an excessive amount of brain cells, which die off. The UCLA researchers found that a rise in a chemical system known as 'tonic inhibition' immediately after a stroke causes a reduction in this level of excitability. But while this 'damping down' initially helps limit the spread of stroke damage, the increased tonic inhibition level and reduced brain excitability persists for weeks, eventually becoming detrimental to the brain's recovery. ... It was surprising to find that the level of tonic inhibition was increased for so long after stroke and that there was an inflection point where the increased level eventually hindered the brain from recovering. It was also surprising that we could easily manipulate tonic inhibition in the brain after stroke to restore it back to a normal, 'non-stroke' level and, in doing this, enhance behavioral recovery. ... They found that by applying specific blockers of this inhibitory brain chemical, they could then 'turn off the switch.' The resulting enhanced brain excitability immediately improved behavioral recovery after stroke."
STUDYING LONGEVITY GENES IN THE AMISH
Thursday, November 4, 2010
Some studies on the genetics of human longevity have looked at small, homogeneous populations - this makes the task easier for a number of reasons. Here is another example: "The advantage of working with a homogeneous population is, you're reducing the variances that can be associated with the environment. [Mennonites and Amish] don't drink, don't smoke. Most do some sort of physical activity. They don't sit around working on a computer all day. ... 5 percent of healthy Amish octogenarians have 'haplogroup X,' a genetic pattern within the mitochondria, which are the regions of cells that generate energy and help guard against deterioration. Haplogroup X is generally found in only 2 percent of Europeans, from whom the Amish descended. In the University of Miami study, only 3 percent of the control group - Amish people who had made it to 80 but suffered from significant disease or disability - had the genetic variant. ... Mitochondria have their own DNA, which is passed down from the mother only. This unique chromosome has variations, called haplogroups. Nine such haplogroups have been well characterized in people of European descent ... But only haplogroup X was found to be prevalent among healthy aged people in the University of Miami study." As we know, some people have better mitochondria; a side-effect of technologies that allow us to replace damaged mitochondrial DNA throughout the body would be the ability to upgrade to a better haplotype. That benefit is tiny, however, compared to the benefit of removing the damage that contributes to degenerative aging.
DECELLULARIZATION FORGING AHEAD
Wednesday, November 3, 2010
The technique of stripping cells from a donor organ and repopulating the extracellular matrix with a patient's own cells is moving ahead, as illustrated by this article: "Spain, a world leader in human organ transplants, is now also a pioneer in the creation of bioartificial organs with stem cells implanted into patients after the opening on Tuesday in Madrid of the first laboratory in the world dedicated to the growth of artificial organs for human transplant. The laboratory will 'empty' human hearts or other human organs unsuitable for transplantation and recolonize their cell content with the patient's stem cells, allowing the organs to grow anew, ready for tranplant back into the new body ... Transplantation of such organs could a daily reality in 'between five and ten years' ... So far, the cardiology unit of the Gregorio Maranon has 'applied the elimination of cells' to eight hearts that have succesfully become viable organs using the patient's stem cells. And by late 2010 they want to install a heart from a donor using regenerated cells. Moreover, 'as it advances, [we could also use] animal organs.'" The downside of decellularization as a technology is that it does still require a donor organ - it is essentially a way of working around the present inability to build a suitably structured framework for an artificial organ. Since replacing all of the cells largely eliminates immune rejection issues in a transplant procedure, there is no reason not to use animal organs, however. They should be just as effective.
NRF2 AND SPECIES LONGEVITY
Wednesday, November 3, 2010
Nrf2 has shown up in past research as a part of the mechanisms of hormesis induced longevity, and here researchers make a pitch for its importance: "Although aging is a ubiquitous process that prevails in all organisms, the mechanisms governing both the rate of decline in functionality and the age of onset remain elusive. A profound constitutively upregulated cytoprotective response is commonly observed in naturally long-lived species and experimental models of extensions to lifespan (e.g., genetically-altered and/or experimentally manipulated organisms), as indicated by enhanced resistance to stress and upregulated downstream components of the cytoprotective nuclear factor erythroid 2-related factor 2 (Nrf2)-signaling pathway. The transcription factor Nrf2 is constitutively expressed in all tissues, although levels may vary among organs, with the key detoxification organs (kidney and liver) exhibiting highest levels. Nrf2 may be further induced by cellular stressors ... The Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activating the transcription of more than 200 genes that are crucial in the metabolism of drugs and toxins, protection against oxidative stress and inflammation, as well as playing an integral role in stability of proteins and in the removal of damaged proteins via proteasomal degradation or autophagy. Nrf2 interacts with other important cell regulators such as tumor suppressor protein 53 (p53) and nuclear factor-kappa beta (NF-kappaB) and through their combined interactions is the guardian of healthspan, protecting against many age-related diseases including cancer and neurodegeneration. We hypothesize that this signaling pathway plays a critical role in the determination of species longevity and that this pathway may indeed be the master regulator of the aging process."
SALAMANDERS AND REGENERATION RESEARCH
Tuesday, November 2, 2010
Maria Konovalenko looks at research into salamander biochemistry: "By tracking individual cells in genetically modified salamanders, researchers have found an unexpected explanation for their seemingly magical ability to regrow lost limbs. Rather than having their cellular clocks fully reset and reverting to an embryonic state, cells in the salamanders' stumps became slightly less mature versions of the cells they'd been before. The findings could inspire research into human tissue regeneration. ... The cells don't have to step as far back as we thought they had to, in order to regenerate a complicated thing like a limb. There's a higher chance that human or mammalian cells can be induced into doing the same thing. ... People working on stem cells are trying to de-differentiate cells in an artificial fashion. It will be very important for the regenerative-medicine community to take stock of what's going on in the salamander, because they've been doing it for 360 million years, and found a natural way to de-differentiate their tissues."
THOUGHTS ON AGING
Tuesday, November 2, 2010
Thoughts on aging from Hybrid Reality: "In the 2050 family picture, there will be many siblings in their 60s with graying hair, a handful of adult children with their spouses, and just two or three grandchildren. It's a strange picture: a family with more older people than younger people. Everything we've grown up seeing in our families and neighborhoods is contrary to this picture. Yet this is exactly the kind of family that will dominate the middle and late half of the 21st century. We're moving to a world of old people, and unless science can radically stop the aging process, that family will be yours in 2050. ... Old age brings maladies like diabetes, Parkinson's, Alzheimer's; it makes one tired easily, unable to sleep well, or run and have sex easily; it makes one's metabolism slow, one's bones brittle, and one's skin wrinkled. In other words, old age is not fun. Frankly, it is hard to argue with the fact that old age is generally more unpleasant than youth. [Aubrey de] Grey believes that science is capable of stopping the aging mechanisms of our bodies. If he receives the funding he needs, he is convinced that we can decouple chronological age from biological age, i.e. even if we're chronologically 70 years old, for instance, our bodies can biologically look and feel as if they're 50, 30 or even 20 years old. ... Which world do you want to live in: the gray world or the youthful world? If you support the young world, you need to push the FDA to treat aging like a disease so that anti-aging research can be funded, and perhaps even write a check to the SENS Foundation started by Aubrey de Grey. ... You need to act today: your future family portrait depends on it."
KIRKWOOD ON GENDER DIFFERENCES IN LONGEVITY
Monday, November 1, 2010
Researcher Thomas Kirkwood revisits the well known difference in life expectancy between the genders: "It turns out that the females of most species live longer than the males. This phenomenon suggests that the explanation for the difference within humans might lie deep in our biology. ... Many scientists believe that the aging process is caused by the gradual buildup of a huge number of individually tiny faults - some damage to a DNA strand here, a deranged protein molecule there, and so on. ... We might well ask why our bodies do not repair themselves better. Actually we probably could fix damage better than we do already. In theory at least, we might even do it well enough to live forever. The reason we do not, I believe, is because it would have cost more energy than it was worth when our aging process evolved long ago, when our hunter-gatherer ancestors faced a constant struggle against hunger. ... If you can avoid the hazards of the environment for a bit longer by flying away from danger or being cleverer or bigger, then the body is correspondingly a bit less disposable, and it pays to spend more energy on repair. Could it be that women live longer because they are less disposable than men? This notion, in fact, makes excellent biological sense. In humans, as in most animal species, the state of the female body is very important for the success of reproduction. The fetus needs to grow inside the mother's womb, and the infant needs to suckle at her breast. So if the female animal's body is too much weakened by damage, there is a real threat to her chances of making healthy offspring. The man's reproductive role, on the other hand, is less directly dependent on his continued good health."
DECELLULARIZATION IN LIVER TISSUE ENGINEERING
Monday, November 1, 2010
Decellularization is a recently developed technique that allows researchers to work around the present inability to create the complex three dimensional framework that supports the cells of an organ. Here it is demonstrated in a liver: scientists "have reached an early, but important, milestone in the quest to grow replacement livers in the lab. They are the first to use human liver cells to successfully engineer miniature livers that function - at least in a laboratory setting - like human livers. The next step is to see if the livers will continue to function after transplantation in an animal model. ... To engineer the organs, the scientists used animal livers that were treated with a mild detergent to remove all cells (a process called decellularization), leaving only the collagen 'skeleton' or support structure. They then replaced the original cells with two types of human cells: immature liver cells known as progenitors, and endothelial cells that line blood vessels. The cells were introduced into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. This network of vessels remains intact after the decellularization process. The liver was next placed in a bioreactor, special equipment that provides a constant flow of nutrients and oxygen throughout the organ. After a week in the bioreactor system, the scientists documented the progressive formation of human liver tissue, as well as liver-associated function."