Fight Aging! Newsletter, March 21st 2011

March 21st 2011

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!



- Making the Vegas Group a Reality
- The Global Forum for Longevity
- Finding Smart Ways to Say Stupid Things
- RasGrf1 Deficiency Extends Life By 20% in Mice
- Stem Cells Help Heal Long-Damaged Hearts
- Discussion
- Latest Headlines from Fight Aging!


What is the Vegas Group? It is a fictional creation that I use to illustrate what I believe needs to happen over the next ten to fifteen years in longevity science in order to work around the oppressive level of regulation in the US and Europe. In brief, I suggest recruiting the growing open biotechnology community to work on the published results in longevity science now emerging from the laboratory, in order to adapt them for human use and medical tourism in Asia-Pacific countries. The science is moving very rapidly, but Western regulators presently forbid development of treatments for aging - so nothing much happens after new biotechnologies are established and demonstrated in laboratory animals like mice.

That gap between demonstrated knowledge and human-ready biotechnology is one that could be filled by the open biotech community - speeding progress towards viable, usable technologies of rejuvenation. These efforts need to happen in order to (a) produce therapies that can be used as soon as possible, and (b) produce meaningful change in the regulatory environment by making longevity medicine available through medical tourism:

"It is clear to me that this sort of strategy will be (and is) very necessary as a part of the process of pushing the bounds of medical technology - which is advancing nowhere near as rapidly as it might be. Stunning progress in the laboratory doesn't translate into stunning progress in the clinic, and this is because of the oppressive shroud of regulation weighing down the entire industry. Can you imagine a world in which it took ten years and a government agency to clear the latest innovations in processors and hard drives? We'd still be stuck with 70s-era computers, and paying ten times the price. Yet in medicine, this is exactly the situation we find ourselves in; a worse product, slow progress, and massive expense.

"By way of a reminder, it is illegal in the US to commercially develop and market medical technologies for the purpose of slowing or reversing aging. I'll stop to let that sink in for a moment, for those of you who didn't know this. The unelected and largely unaccountable bureaucrats of the FDA do not recognize aging as a disease, therefore will not approve any treatment for aging - and so anyone who forges ahead to try it will be shut down and prosecuted. If you ever wondered why, in this age of remarkable advances and plummeting costs in biotechnology, there are not a thousand startup companies striking out to take on aging itself ... well, this is why.

"So I have been pondering how best to make the vision of the Vegas Group a reality: what steps do we take so that we wake up six or seven years from now to an open source biotech community whose members are working on enabling the best longevity therapies produced by the formal research community - and who have the overseas connections to enable responsible use of resulting therapies in a clinical setting. ... In many ways, I see this sort of thing as the answer to 'what comes next after the SENS Foundation?' When the SENS Foundation is forging through the waves five years from now, making progress and getting things done in repairing the biochemical damage of aging, what are the new and energetic research-focused organizations springing up at that time? How are they organized? What are their strategies for turning this growing sea of practical possibilities for repairing aging into therapies for humans?"


The forthcoming Global Forum for Longevity is organized by a large insurance group, and this is not all that unusual:

"The Global Forum for Longevity is an industry-sponsored forum taking place later this month; fairly mainstream, no talk of radical life extension or other forms of futurism that might lead to intellectual discomfort for some. I mention it because it is a symptom of the growing interest in biogerontology on the part of the vast insurance industries of the world - which should not be a surprising phenomenon. To find people likely to pay close attention to the future of longevity science, you want to look amongst the folk who stand to gain or lose a great deal of money due to changes in human life spans. Life insurance, pensions, and other forms of making money through managing statistical risks on life expectancy data are, taken together, a very big business indeed.

"So here an insurance conglomerate is, as many of them are, sponsoring an event to help spread knowledge through the system: from scientists to actuaries to risk managers and other decision makers in the food chain. Building bridges and forming communities is in and of itself a form of risk management in the long term: it is a way to lower the likelihood of unpleasant surprises by trying to better understand what the scientific community believes are likely outcomes for longevity science over the decades ahead."


A great many arguments fielded by those who oppose enhanced human longevity are not even worthy of response. Some examples of the type can be found in this Fight Aging! post:

"[Nicholas Agar] begins by suggesting that de Grey's 'Strategies for Engineered Negligible Senescence' (SENS) might create an obsessive fear of death, which might come to completely dominate the lives of those who adopted such strategies. Agar worries that, because negligibly senescent people would have more years of life to lose if they failed in one of their projects, they would have a strong reason not to take any risks at all. Indeed, at this point he invokes the concern that later in the book he will call its central theme: the concern about alienation, about becoming separated from the kinds of, here, risky experiences that constitute human lives as we know them. According to Agar, de Grey's ambition to radically extend our lives 'is likely to alienate us from the things and people who currently give our lives meaning'."

There is little you can do in the face of such arrant nonsense but shrug and move on. Some people are so fearful of the prospect of change that they throw up words as a wall, any words, any argument, no matter how hollow or silly. And it is silly to suggest that people with more years to lose will necessarily take fewer risks - after all, which segment of our present population takes on the lion's share of risky behavior here and now? That would be the young, with their lives ahead of them.


Last year it was discovered that mice created from two female parents live significantly longer. The reason is thought to be a deficiency in RasGrf1, and recent research shows that mice specifically engineered for that deficiency also live longer:

"A recent open access paper from a Spanish research group outlines yet another methodology to add to the growing list of ways to increase healthy life span in mice. Progress is signified by diversity these days; there are, I think, more than twenty different demonstrated methods of bringing about meaningful extension of life in mice as of today. ... We observed that mice deficient for RasGrf1-/- display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals.
Aged RasGrf1-/- displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1-/- [and] the blood metabolomic profiles of RasGrf1-deficient mice resembled those observed in calorie-restricted animals."


A recent clinical trial of an autologous stem cell therapy shows that even old, unhealed damage can be at least partially repaired by these first generation treatments:


"Researchers have shown for the first time that stem cells injected into enlarged hearts reduced heart size, reduced scar tissue and improved function to injured heart areas. ... The injections first improved function in the damaged area of the heart and then led to a reduction in the size of the heart. This was associated with a reduction in scar size. The effects lasted for a year after the injections, which was the full duration of the study ... This therapy improved even old cardiac injuries. [Some] of the patients had damage to their hearts from heart attacks as long as 11 years before treatment."


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, March 18, 2011
The modest goals of the mainstream longevity science community are outlined by one of its members in this article - to enable everyone to age as slowly as only some people presently do. No radical life extension or rejuvenation, as would be enabled by the damage repair approach to longevity science, but rather just a gentle slowing of aging, enabled by technologies that would probably not emerge in time to benefit those of us in middle age today. "It is the aging of our cells that causes us to develop most diseases, says Dr. Nir Barzilai, professor of medicine and genetics at the Albert Einstein College of Medicine in New York. 'We know this, paradoxically, because of the amazing success we have had in treating heart disease. We have been able to save people from heart attacks with stents and bypass surgery - only to find that within a year or two they develop Alzheimer's, diabetes or cancer at an alarming rate. Why? Because we have never treated the underlying aging of their cells. We have simply treated the disease manifestation.' So, explains Barzilai, if we can find the processes in the body that control aging and find a way to treat them, we will be able to protect people from the diseases of aging. Barzilai heads a unique longevity study of more than 500 people who have reached the age of 100. The LonGenity study is looking at the genetic makeup of centenarians to identify the biological markers that explain why they live so long and so well. Because the remarkable thing about these people is not simply that they live to the age of 100, it is that they live to 100 in pretty good health. Just why they live that long without getting sick and dying is what Barzilai wanted to find out."

Friday, March 18, 2011
Via EurekAlert!: "A gene therapy called NLX-P101 dramatically reduces movement impairment in Parkinson's patients, according to results of a Phase 2 study ... The approach introduces a gene into the brain to normalize chemical signaling. ... The study is the first successful randomized, double-blind clinical trial of a gene therapy for Parkinson's or any neurologic disorder ... Half of patients receiving gene therapy achieved dramatic symptom improvements, compared with just 14 percent in the control group. Overall, patients receiving gene therapy had a 23.1 percent improvement in motor score, compared to a 12.7 percent improvement in the control group. ... Improved motor control was seen at one month and continued virtually unchanged throughout the six-month study period. ... Gene therapy is the use of a gene to change the function of cells or organs to improve or prevent disease. To transfer genes into cells, an inert virus is used to deliver the gene into a target cell. In this case, the glutamic acid decarboxylase (GAD) gene was used because GAD makes a chemical called GABA, a major inhibitory neurotransmitter in the brain that helps 'quiet' excessive neuronal firing related to Parkinson's disease. ... In Parkinson's disease, not only do patients lose many dopamine-producing brain cells, but they also develop substantial reductions in the activity and amount of GABA in their brains. This causes a dysfunction in brain circuitry responsible for coordinating movement."

Thursday, March 17, 2011
Researchers recently demonstrated that increased cellular housekeeping could slow neurodegeneration, and here a different group show the same outcome: "Cells, which employ a process called autophagy to clean up and reuse protein debris leftover from biological processes, were the original recyclers. A team of scientists [have] linked a molecule that stimulates autophagy with the reduction of one of Alzheimer's disease's major hallmarks, amyloid peptide. Their finding suggests a mechanism that could be used to eliminate built-up proteins in diseases such as Alzheimer's, Down syndrome, Huntingdon's and amyloid-beta, the protein aggregates that cause Alzheimer's plaques. Increasing autophagy, either through a drug or a natural process such as diet, could improve the outcome for people with neurodegenerative diseases ... The researchers [tested] various compounds for their ability to reduce the buildup of amyloid-beta by exposing cultured cells to compounds known to activate autophagy. They then compared the effect of these compounds by removing growth factors from the culture medium, a well-established stimulant of autophagy known as 'starvation.' The researchers found that SMER28 was the most effective compound, and focused their studies on it to characterize the cellular components involved in this phenomenon. They compared the effect of SMER28 on amyloid-beta formation using normal cells or cells where the expression of genes known to be involved in autophagy was reduced or abolished. They found that three important autophagic players were involved, and one of them was essential for SMER28's effect."

Thursday, March 17, 2011
The present generation of therapies for rheumatoid arthritis are based on TNF inhibition - a fairly crude manipulation of the immune system when considered in the grand scheme of what is possible, but one that is getting better. From Technology Review: "A new protein engineered to inhibit molecules that cause inflammation not only reduces symptoms of rheumatoid arthritis in mice but also may have potential to reverse the disease's course. Researchers hope the findings will point toward a new therapy for this crippling and difficult-to-treat disease, which occurs when the immune system attacks the body's own joints. Even medications that are most successful in halting joint inflammation are effective in only about half of the patients who try them. ... The new synthetic protein [appears] to target TNF in a far more specific fashion and could be produced at a small fraction of the cost [of present TNF inhibitors]. ... a protein called progranulin binds to TNF receptors and that administering the protein to mice with rheumatoid arthritis reduced or even eliminated their symptoms. Then they determined which fragments of progranulin were responsible for binding to TNF and combined those fragments to engineer a protein that works even better to suppress disease. Mice with mild arthritis appeared to be disease-free after several weeks of regular injections of the modified progranulin."

Wednesday, March 16, 2011
Nanotechnology can be used to build assemblies of designed molecules that seek out specific cells - such as cancer cells - but an alternative approach to targeted therapies is to build machinery large enough to be controlled from outside the body, such as the microcarriers demonstrated here: "Soon, drug delivery that precisely targets cancerous cells without exposing the healthy surrounding tissue to the medication's toxic effects will no longer be an oncologist's dream but a medical reality ... sing a magnetic resonance imaging (MRI) system, [researchers] successfully guided microcarriers loaded with a dose of anti-cancer drug through the bloodstream of a living rabbit, right up to a targeted area in the liver, where the drug was successfully administered. This is a medical first that will help improve chemoembolization, a current treatment for liver cancer. ... The therapeutic magnetic microcarriers (TMMCs) [are made] from biodegradable polymer, [measure] 50 micrometers in diameter - just under the breadth of a hair - [and] encapsulate a dose of a therapeutic agent (in this case, doxorubicin) as well as magnetic nanoparticles. Essentially tiny magnets, the nanoparticles are what allow the upgraded MRI system to guide the microcarriers through the blood vessels to the targeted organ. During the experiments, the TMMCs injected into the bloodstream were guided through the hepatic artery to the targeted part of the liver where the drug was progressively released."

Wednesday, March 16, 2011
Because veterinary medicine is less (oppressively) regulated than human medicine, animals are benefiting from stem cell therapies that are safe enough for human use but nonetheless still illegal to commercially develop in the US: "In a very unusual breakthrough, a stem cell treatment for racehorses is ready to be tried ... on you. British scientists pioneered a technique in horses where an individuals' own stem cells are grown outside the body, then injected into the damaged tendon. There will be a clinical trial in the UK in which 24 human patients will undergo this radical new stem cell treatment for similar tendon injuries. We'll tell you about the proven benefits in racehorses so you'll understand the possible benefits in people. The test subjects who join the clinical trial will be in the unique position of enjoying a medical procedure that is years behind the veterinary equivalent. If human beings have the same barely believable 80% recovery rate, this will be a leap forward for sports medicine. ... The reason animals can get commercial drugs and treatments faster than people in the US and other Western countries is simple: there is enormous oversight in human medical research. Veterinary research is comparably simple. According to the FDA, bringing a new drug to market for humans requires pre-clinical laboratory tests, animal tests, and human clinical trials. Each one of those steps costs money, lots and lots of it. Approval for veterinary drugs is simpler, requiring a single study that proves the drug is safe and effective. Because of regulatory difference, progress on animal medical research can move very quickly compared to human research."

Tuesday, March 15, 2011
The frailty and degenerations of aging impose enormous costs on sufferers and those who assist them - one of many reasons to accelerate work on repairing the biochemical damage that causes aging: "Nearly 15 million people in the United States take care of a loved one with Alzheimer's disease or another form of dementia, amounting to 17 billion hours or more than $202 billion in unpaid care ... If these caregivers all lived in one U.S. state, it would be the nation's fifth largest, according to the Alzheimer's Association's 2011 annual report on the disease. The report illustrates the growing burden of Alzheimer's disease, a fatal brain-wasting disease that erodes memory, thinking, behavior and the ability to handle daily activities. Alzheimer's affects more than 26 million people globally and can stretch on for years, slowly robbing patients of their mind and memories. And there are currently no drugs that can keep the disease from progressing. ... The group estimates that 5.4 million people in the United States are now living with Alzheimer's disease, up from 5.3 million a year ago. That includes 5.2 million people over age 65 or about one in eight senior citizens. A 65-year-old person diagnosed with Alzheimer's typically lives four to eight years after being diagnosed, but some patients live as long as 20 years after diagnosis. ... The $202 billion in unpaid care is on top of the $183 billion estimate for Alzheimer's care expected to be delivered in 2011 by healthcare workers in homes, hospitals and long-term care facilities."

Tuesday, March 15, 2011
Proteins generated by the gene p16INK4a are thought to be a biomarker for aging, and in this open access paper a connection with calorie restriction (CR) is explored: "Epigenetic events are among the most striking mechanisms responsible for nutrition-related longevity, which is believed to dynamically regulate gene expression by primarily impacting two epigenetic codes, DNA methylation and histone modification. As evidence of this, the yeast protein silent information regulator 2 (Sir2) [is] a key determinant in CR-induced lifespan prolongation in yeast. In mammalians, SIRT1 is one of seven mammalian orthologs of Sir2, which has been extensively studied for its roles in chromatin remodeling and lifespan elongation. SIRT1 acts as a nutrient sensor involved in the regulation of various gene expressions as well as modulation of important signal transductions either directly or indirectly through its unique epigenetic effects, which ultimately influence the regulation of longevity. Our previous studies indicated that glucose restriction-induced DNA methylation alteration in the p16 promoter contributes to cellular lifespan extension. In this regard, epigenetic mechanisms are major molecular events which play a crucial role in CR-induced longevity. Therefore, we speculated that an aging-associated gene such as p16 may have a central position in epigenetic control of inhibition of cellular senescence and lifespan elongation in response to CR."

Monday, March 14, 2011
Longevity corresponds very well with the general level of wealth and technology in society. This is well illustrated by the transformation of South Korea over past decades, as well as by historical periods such the 17th and 18th centuries in England. Here Gapminder provides an interactive visualization of how both wealth and health have advanced in lockstep over the past century - there is always inequality between and within regions of the world, but the overall direction of progress is onward and upward. Some of you have no doubt seen this before, as the topic is a common one here at Fight Aging!, but this visualization is a quality product and well worth pointing out again. I'll leave you with an appropriate quote to think on: "200 years ago, all countries were poor and life expectancy was less than 40 years. In the 1800s, health only improved in a few countries, but today no country has less than 40 years in life expectancy."

Monday, March 14, 2011
From the most recent edition of Cryonics Magazine: "Alcor Life Extension members now have access to nationwide standby, stabilization and transport services provided by teams of medical professionals through Suspended Animation, Inc., but some Alcor members may be unfamiliar with Suspended Animation, the company. Founded in 2002, Suspended Animation, Inc. (SA) serves cryonicists in the continental United States from all cryonics companies through contracts with individuals and their membership and long-term care organizations. SA is not a membership organization and does not offer long-term cryonics care, but instead focuses its efforts on research and development of superior equipment and services for cryonics. Over the years, SA has developed or modified a variety of equipment suitable for air travel and used for cryonics applications, including portable ice-baths, custom stabilization kits and two patient care and transport vehicles now deployed in California and Florida. SA's current research and development projects are an automated, air-transportable liquid ventilation device (in conjunction with Critical Care Research) for rapid cooling of cryonics patients; an automated whole body vitrification system (based on a proprietary 21st Century Medicine, Inc. system currently used in animal research), and using cell death gene expression profiling to evaluate existing and new cryonics stabilization strategies."



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