Fight Aging! Newsletter, July 23rd 2012

July 23rd 2012

The Fight Aging! 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 Fight Aging!



- More Press for the 2045 Initiative
- Video From the Genetics of Aging and Longevity Conference
- Does Anyone Really Care About Living Longer?
- Discussion
- Latest Headlines from Fight Aging!
    - Adding More Data to the Role of Nuclear DNA Damage in Aging
    - Possible Early Antibody Therapy for Alzheimer's Disease
    - Rapamycin Versus Macular Degeneration
    - Testing Blanket Blood Pressure Medication in Older People
    - Nanoscale Scaffolds and Stem Cells for Cartilage Repair
    - Linking Oxidative Stress With Age-Related Immune Decline
    - Alcor Donates to Brain Preservation Prize, is Declined
    - A Profile of Kenneth Hayworth, Brain Preservation Prize Founder
    - An Example of an Early Targeted Cancer Therapy
    - Progress in Building Muscle Tissue For Transplant


You'll no doubt recall the 2045 initiative backed by an enthusiastic high net worth Russian individual, which appears so far to be the opening stages of a serious long-term effort to convert a fraction of that net worth into the technologies needed for artificial, non-biological bodies capable of indefinitely supporting a human brain - and after that to move on to brain emulation and mind uploading:

"To my eyes, the most interesting aspect of this Russia 2045 initiative is that, unlike any other serious proposal I'm aware of, their focus is on getting out of biology and into machine bodies as rapidly as possible. ... In essence, this is a course to throw away as much of the body as possible as soon as possible - a path based on a different set of preconceptions about difficulty and efficiency on the road leading to an artificial brain hosting a once-biological human mind.

"First up is the development of robots that can be controlled by the human mind. After that, and ideally within 10 years, Itskov wants to develop robots that can actually host a flesh-and-blood human brain, via surgical transplant. In twenty years time, things get even more interesting: Itskov anticipates 'uploading' the contents of the human brain into a robot, yielding eternal life via artificial body. By 2045, he'd like to replace those 'bots entirely - with holograms. Since February, Itskov has stayed plenty busy working on his 'Avatar' plan ... With a lab of scientists reportedly already working on the program in Russia, Itskov has now branched out to the U.S, with plans to open a San Francisco office this summer and host a futurity conference - called Global Future Congress - in New York later this year.

"His next step: Itskov has published an open letter to the world's richest people, urging them to back the initiative - and consider volunteering themselves as potential avatars. 'I urge you to take note of the vital importance of funding scientific development in the field of cybernetic immortality and the artificial body. Such research has the potential to free you, as well as the majority of all people on our planet, from disease, old age and even death.'

"I'm of the opinion that this is not the most optimal path towards the defeat of aging, based on my understanding of the relative difficulty of building a full-featured neural interface and life support system for the brain versus realizing rejuvenation biotechnology that can repair the biological chassis we have now - even leaving aside the issue that an uploaded or emulated copy of your mind is just a copy of you, not you. In the long run we will all be wholly artificial, of course, but it seems premature to be aiming for that now versus after the advent of molecular nanotechnology and the capacity to build functional replacements for biological components (e.g. blood cells, brain cells, and so forth) that are better than the original. It is, however, very important for the general future of engineered longevity to have a diversity of approaches, disagreement, and enthusiastic people with resources and vision. At the very least, in a world in which artificial bodies are being developed with the stated goal of preventing people from aging to death, it becomes that much easier to gather support for work on the biotechnologies that can repair the damage of aging."


The Science for Life Extension Foundation helped organize the 2nd International conference on the Genetics of Aging and Longevity, held back in April in Moscow. Thanks to the Foundation staff, video from the conference is starting to make its way to a YouTube channel:


If you want to judge by actions rather than words, the answer might be quite close to "no":

"Regular exercise can extend life, but 90% of humanity would rather die than submit to a daily workout. ... Last week, an international conference in Brazil heard from scientist Professor Frank Booth, who gave a talk about how the lack of physical activity can be shown to significantly reduce lifespan. The current USA guidelines for physical activity are 30 minutes a day for somebody over 20 years old, but he reported that over 90% of people do not do this amount and are shortening their life as a result.

"Human psychology is hardwired to discount future rewards, a thing called time preference. The future reward that is an increased chance of being alive in sixty years tends to have a lower value for most people than, say, substituting a video game or nap for exercise right now. Sad but true. So there is more gaming, less exercise, and shorter lives on balance. Time preference is pretty good in the environment in which we evolved, but becomes increasingly less helpful the more civilized and technologically enabled that environment becomes.

"So equally, if low-cost life-extending therapies existed - along the lines of the rejuvenation biotechnologies proposed by the SENS Foundation - and not using them was viewed as something akin to failing to brush your teeth, then many of the same people who skip exercise would make the effort to head to the clinic every few years and thereby live longer. Social pressure also enters into value judgments, a cost to be measured alongside others. It is entirely possible that people of future years will be using longevity medicine for reasons that have little to do with their own longevity; after all, they will still be operating with the same time preference as we do. Being alive sixty years in the future has a small value for the average human being.

"This is one of the reasons why so very many people make themselves more sick than they have to be, and die younger than they might have. They didn't take care of themselves, despite knowing that they could do a better job. Separately, but a part of the same pattern of psychology, today there exists the realistic prospect of building actual, working means of rejuvenating the old. The path to achieving that end is just about as clear, straightforward, and well defined as medical research can ever be. We know what needs to be fixed, and there are numerous proposals for ways to fix it. But the public at large is not yet rallying to this cause.

"A cynic might say that they never will, and cite human nature as outlined above. Fortunately, it isn't necessary to persuade everyone. Even a sizable minority will be enough. We can point to successful minority support for research and development in many age-related diseases, for example - large research communities work on the common conditions of aging, despite that fact that everything said about aging and the value of life in the future applies there. There are ways around the basic problem of time preference as it applies to raising support for the medicine of human longevity. We just have to keep working away at it, just like the pioneers who built successful research communities for cancer, heart disease, dementia, and many other conditions that plague the old."


The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!



Friday, July 20, 2012
We accumulate random nuclear DNA damage - mutations - as we age. This is understood to increase the risk of cancer, as the more mutations that occur the greater the chance that one will be of the rare type that can spawn a cancer, but there is some debate over the degree to which nuclear DNA damage contributes to aging itself. Here researchers add some more data to the picture: "Hundreds of mutations exist in leukemia cells at the time of diagnosis, but nearly all occur randomly as a part of normal aging and are not related to cancer, new research shows. [Researchers] have found that even in healthy people, stem cells in the blood routinely accumulate new mutations over the course of a person's lifetime. And their research shows that in many cases only two or three additional genetic changes are required to transform a normal blood cell already dotted with mutations into acute myeloid leukemia (AML). ... The study is the first to investigate how often mutations typically develop in healthy stem cells in the blood. ... In recent years, [researchers] have sequenced the genomes of 200 patients with AML to try to understand the mutations at the root of the disease. Without fail, each patient's leukemia cells held hundreds of mutations, posing a conundrum for scientists, who have long believed that all the mutations in a cancer cell are likely to be important for the disease to progress. ... But we knew all of these mutations couldn't be important. It didn't make any sense to us that so many mutations were present in all the cells in the tumor. ... Every person has about 10,000 blood stem cells in their bone marrow, and the researchers found that each stem cell acquires about 10 mutations over the course of a year. By age 50, a person has accumulated nearly 500 mutations in every blood stem cell. ... Mutations are known to develop in cells as we age, but no one had any idea how many mutations occur in blood stem cells and how frequently they develop. These random, background mutations occur during cell division and are unrelated to cancer. Our DNA can tolerate a huge number of these hits without any negative consequences. But if a cancer-initiating event occurs in one of these stem cells, it captures the genetic history of that cell, including the earlier mutations, and drives leukemia to develop. ... scientists were surprised to see that the total number of mutations varied by age, not by whether a patient had leukemia. Thus, a healthy person in his 40s had just about the same number of mutations in his blood stem cells as a leukemia patient of the same age had in his cancer cells."

Friday, July 20, 2012
From the MIT Technology Review: "Alzheimer's patients given a drug that is already used to treat immune disorders saw their condition stabilize in a small study presented at a conference this week. Study participants were given the compound - known as intravenous Ig, or IVIg - for three years. During this period, they showed no signs of further cognitive decline or memory loss. ... All participants in the study had mild to moderate Alzheimer's disease. Only four received the optimal dose of IVIg over three years. These patients showed no decline from their baseline state in cognition, memory, daily functioning, or mood - all expected effects of the disease. Patients who initially received a placebo but were later switched to IVIg treatment declined more slowly while receiving the drug. IVIg [contains] a mixture of antibodies isolated from the pooled plasma of blood donated by healthy people. The assumption is that this blood by-product contains antibodies from the healthy donors that attack the damaged proteins in Alzheimer's patients. ... such results [should] inspire a large number of scientific studies aimed at identifying the functional ingredients in the immune mixture, so that others could potentially develop a synthetic form. ... I really do hope that it turns out to work, because then it gives a good platform to start finding out what components are in there, What is it in the IVIg - is it selective antibodies against beta-amyloid, against tau, or something else?"

Thursday, July 19, 2012
A commentary on testing rapamycin as a therapy for age-related macular degeneration (AMD): "Although neovascular AMD only accounts for less than 15% of the overall age-related macular degeneration, it is responsible for over 80 percent of the severe vision loss cases. ... It was reported in 2004 that rapamycin (trade name sirolimus) treatment significantly reduced the extent of neovascularization [induced] in adult mice ... In an advance online publication this year [Kolosova et al] presented exciting results that rapamycin could actually prevent AMD-like retinopathy in an aging rat model that more closely resembles human AMD pathology. They investigated the effect of rapamycin on spontaneous retinopathy in senescence- accelerated OXYS rats. OXYS rats were treated orally with either 0.1 or 0.5 mg/kg rapamycin, which was given together with food. Rapamycin was found in a dose-dependent manner to reduce the incidence and severity of retinopathy, and attenuated AMD disease progression. Some histological abnormalities associated with retinopathy were notably reduced ... significantly, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats, suggesting that it is safe."

Thursday, July 19, 2012
What happens if everyone in later years regularly takes common blood pressure and cholesterol medications, even if healthy? Researchers have been running trials: "Results of a randomised trial [show] that a four-component Polypill given to people aged 50 and over to reduce their risk of heart attack and stroke, the most common causes of death worldwide, achieved large reductions in blood cholesterol and blood pressure, the main causes of these two diseases. ... The results observed in the trials had been accurately predicted in an earlier paper [before] any Polypill had been made. The Polypill, a tri-layered tablet, contains three blood pressure lowering medicines and a statin for lowering cholesterol. This was given to people without a history of cardiovascular disease aged 50 or more. They experienced a 12 percent reduction in blood pressure and a 39 percent reduction in LDL cholesterol (the 'harmful' cholesterol), achieving levels typical of people aged 20 years. ... The health implications of our results are large. If people took the Polypill from age 50, an estimated 28 percent would benefit by avoiding or delaying a heart attack or stroke during their lifetime; on average, those who benefit would gain 11 years of life without a heart attack or stroke. ... This is the first trial in people selected on the basis of age alone without the need for a medical examination or tests - setting the scene for the prevention of first heart attacks and strokes in the general population without requiring a medical examination or special tests. ... Our trial shows that the predicted effects of the Polypill can be achieved in practice. The expected impact on preventing what is now the world's leading cause of death is large - about a two-thirds reduction in heart attacks and strokes."

Wednesday, July 18, 2012
Via EurekAlert!: "tissue engineers have used tiny, artificial fiber scaffolds thousands of times smaller than a human hair to help coax stem cells into developing into cartilage, the shock-absorbing lining of elbows and knees that often wears thin from injury or age. ... Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we're building a temporary template that mimics the cartilage cell's natural environment, and taking advantage of nature's signals to biologically repair cartilage damage. ... Unlike skin, cartilage can't repair itself when damaged. For the last decade, [researchers have] been trying to better understand the development and growth of cartilage cells called chondrocytes, while also trying to build scaffolding that mimics the cartilage cell environment and generates new cartilage tissue. This environment is a 3-dimensional mix of protein fibers and gel that provides support to connective tissue throughout the body, as well as physical and biological cues for cells to grow and differentiate. In the laboratory, the researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfate [to] serve as a growth trigger. After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow-derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material. ... compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue. ... The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats, and compared the results to damaged cartilage in knees left alone. They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen, a component of cartilage. The nanofiber scaffolds resulted in greater production of a more durable type of collagen, which is usually lacking in surgically repaired cartilage tissue."

Wednesday, July 18, 2012
Mitochondrial damage is one of the reasons that levels of damaging oxidative compounds rise in the body with age - known as oxidative stress. At the level of molecular machinery, having reactive molecules flying around in large numbers will cause important mechanisms to break down more often. It is generally thought that increased oxidative stress contributes to a range of dysfunctions, and here researchers link it with immune system decline: "Aging is known to affect immune function, a phenomenon known as immunosenescence ... Our study has uncovered several ways in which aging can worsen the body's overall ability to mount an effective immune response. ... All cells generate chemicals called free radicals as a normal part of metabolism. These highly reactive, unstable molecules can readily damage proteins, lipids and other cellular components ... Cells keep 'oxidative stress' in check by producing several enzymes that are scavengers of free radicals. But in aging, increased production of free radicals coupled with cells' decreased production of antioxidant enzymes cause a buildup of damaged proteins and other molecules that can be toxic to cells. The current study is the first to examine whether age-related oxidative stress compromises the function of a type of immune cell called dendritic cells. ... When you are exposed to viruses or bacteria, these cells engulf the pathogens and present them to the immune system ... [Researchers] isolated dendritic cells from aging mice and found that oxidation-damaged proteins had accumulated in those cells and had caused harmful effects. For example, oxidatively modified proteins hampered the function of endosomes, the cell's organelle where pathogens are inactivated. When the mice were injected with a potent antioxidant in the abdominal cavity daily for two weeks, some of the effects of oxidative stress were reversed. This finding has implications for designing vaccines or therapies for humans, especially the elderly, whose weakened immune systems increase their susceptibility to infections and cancer, and reduces vaccine effectiveness. ... Many elderly people respond very poorly to vaccination, so perhaps a cycle of therapy with antioxidants before vaccination might improve their immune response to vaccines."

Tuesday, July 17, 2012
These things happen: "How well does cryopreservation (with current methods) work? Is the process sufficiently preserving personal identity-critical information stored in the brain? Are there any alternatives that might be as good or better? Although the Alcor Library already contains evidence that, under good conditions, we are preserving neural connections (the totality of which is now sometimes being referred to as the 'connectome'), more evidence is desirable. The Brain Preservation Foundation is offering a $100,000+ Brain Preservation Technology Prize in order to stimulate the scientific evaluation of such technologies as cryopreservation and chemopreservation (aldehyde or other chemical fixation followed by embedding in solid resin). The goal of the prize is to lead to 'the development of an inexpensive and reliable hospital surgical procedure which verifiably preserves the structural connectivity of 99.9% of the synapses in a human brain if administered rapidly after biological death.' ... A few days ago, Alcor announced that it would contribute $10,000 to the Brain Preservation Foundation toward the costs of testing both cryopreservation and chemopreservation. The Foundation has declined our donation because of concerns that it might be perceived as influencing the judges' decisions. Even though Alcor was not a competitor for the prize, we can understand the Foundation's concern. We will instead look for other ways to validate existing cryopreservation methods, as well as continue to improve them."

Tuesday, July 17, 2012
From the Chronicle of Higher Education: "By 2110, Hayworth predicts, mind uploading - the transfer of a biological brain to a silicon-based operating system - will be as common as laser eye surgery is today. ... While a graduate student at the University of Southern California, he built a machine in his garage that changed the way brain tissue is cut and imaged in electron microscopes. The combination of technical smarts and entrepreneurial gumption earned him a grant from the McKnight Endowment Fund for Neuroscience, a subsidiary of the McKnight Foundation, and an invitation to Harvard, where he stayed, on a postdoctoral fellowship, until April. To understand why Hayworth wants to plastinate his own brain you have to understand his field - connectomics, a new branch of neuroscience. A connectome is a complete map of a brain's neural circuitry. ... He looks at the growth of connectomics - especially advances in brain preservation, tissue imaging, and computer simulations of neural networks - and sees something else: a cure for death. In a new paper in the International Journal of Machine Consciousness, he argues that mind uploading is an 'enormous engineering challenge' but one that can be accomplished without 'radically new science and technologies.' ... to Hayworth, science is about overturning expectations: 'If 100 years ago someone said that we'd have satellites in orbit and little boxes on our desks that can communicate across the world, they would have sounded very outlandish.' One hundred years from now, he believes, our descendants will not understand how so many of us failed for so long to embrace immortality. In an unpublished essay, 'Killed by Bad Philosophy,' he writes, 'Our grandchildren will say that we died not because of heart disease, cancer, or stroke, but instead that we died pathetically out of ignorance and superstition' - by which he means the belief that there is something fundamentally unknowable about consciousness, and that therefore it can never be replicated on a computer."

Monday, July 16, 2012
One of the ways in which new means of targeting therapies to specific cells in the body - such as cancer cells - will arrive in the clinic more rapidly is for their developers to use existing approved drugs. That isn't necessarily the way to build objectively better therapies, but it will cost far less to run the regulatory gauntlet: "researchers have developed a novel system to simultaneously deliver a sustained dose of both an immune-system booster and a chemical to counter the cancer's secretions, resulting in a powerful therapy that, in mice, delayed tumor growth, sent tumors into remission and dramatically increased survival rates. The new immunotherapy incorporates well-studied drugs, but delivers them using nanolipogels (NLGs), a new drug transport technology the researchers designed. The NLGs are nanoscale, hollow, biodegradable spheres, each one capable of accommodating large quantities of chemically diverse molecules. The spheres appear to accumulate in the leaky vasculature, or blood vessels, of tumors, releasing their cargo in a controlled, sustained fashion as the spherule walls and scaffolding break down in the bloodstream. For the recent experiments, the NLGs contained two components: an inhibitor drug that counters a particularly potent cancer defense called transforming growth factor-β (TGF-β), and interleukin-2 (IL-2), a protein that rallies immune systems to respond to localized threats. ... The current study targeted both primary melanomas and melanomas that have spread to the lung, demonstrating promising results with a cancer that is well-suited to immunotherapy and for which radiation, chemotherapy and surgery tend to prove unsuccessful, particularly when metastatic." It's worth remembering that the medicine presently available in the clinic is not really available because it is better for patients, but rather because it is better at getting past regulatory hurdles - these two properties sometimes overlap, but are not the same at all.

Monday, July 16, 2012
Researchers are making progress towards building useful muscle tissue from scratch, suitable for transplant: "exercise is a key step in building a muscle-like implant in the lab with the potential to repair muscle damage from injury or disease. In mice, these implants successfully prompt the regeneration and repair of damaged or lost muscle tissue, resulting in significant functional improvement. ... For the study, small samples of muscle tissue from rats and mice were processed to extract cells, which were then multiplied in the lab. The cells, at a rate of 1 million per square centimeter, were placed onto strips of a natural biological material. The material, derived from pig bladder with all cells removed, is known to be compatible with the body. Next, the strips were placed in a computer-controlled device that slowly expands and contracts - essentially 'educating' the implants on how to perform in the body. ... The next step was implanting the strips in mice with about half of a large muscle in the back (latissimus dorsi) removed to create functional impairment. While the strips are 'muscle-like' at the time of implantation, they are not yet functional. Implantation in the body [prompts] further development. ... The scientists compared four groups of mice. One group received no surgical repair. The other groups received implants prepared in one of three ways: one was not exercised before implantation, one was exercised for five to seven days, and one had extra cells added midway through the exercise process. The results showed that exercising the implants made a significant difference in both muscle development and function. ... The implant that wasn't exercised, or pre-conditioned, was able to accelerate the repair process, but recovery then stopped. On the other hand, when you exercise the implant, there is a more prolonged and extensive functional recovery. Through exercising the implant, you can increase both the rate and the magnitude of the recovery."



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