Longevity Meme Newsletter, March 05 2007

March 05 2007

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology and proven medical advances to live healthy, longer lives.



- More on How Medical Science Progresses
- Looking for SENS In Biomedical Research
- Discussion
- Latest Healthy Life Extension Headlines


Following on from last week's topic - that it's a good idea to gain a better layman's understanding of the science behind efforts to extend the healthy human life span - I thought I'd look at one more facet of science as it is practiced today. How is it that progress happens, knowledge is created, and that a right answer is distinguished from a wrong answer?


"Scientists are human like the rest of us, which means mistakes, poor first tries, over attachment to ideas, institutional bias and other human failings are mixed in with the long record of triumphs and progress produced by the scientific community - people acting in accordance with the scientific method.

"A while back, an examination of just how much research turns out to be wrong caused something of a stir amongst the public at large - no new news to those involved in science, of course, but many people treat the distinct findings of individual scientists and single teams with a touch too much reverence. ... It's one thing to see widely varied, changing, contradictory information presented by reputable researchers - but it's quite another to be able to put this in context, as a part of an ongoing and very human process, and therefore understand the likely weight behind each position."

When reading up on scientific research (or claims of scientific support for any given position), always verify and look for replication of results or other, similar work. Just over half of all new results in a sparsely researched field turn out to be wrong in some way, later corrected as more scientists come to work on the issue at hand. Very few new results are useless, however, for all they are wrong: science is a process, and just like every other process is matter of demonstrating that you are wrong, coming to understand why you are wrong, and using that new information to move forward until the weight of evidence demonstrates that you are right.


The next time you are reading about SENS, the proposed Strategies for Engineered Negligible Senescence, an engineering plan for repairing the biochemical damage that is aging, you should take a little time to find the threads of SENS elsewhere in the research community. They are there: SENS is not de novo science pulled from the air, but rather is a combination - and proposed further development - of present research from many different fields within medicine.


To pick one example, let's look at the contribution of free radical damage in the mitochondria to aging. By way of a reminder, your mitochondria, the cellular power plants, produce a steady flow of damaging free radicals as a part of their normal operation. As a result, they become damaged, and cells filled with damaged mitochondria spin out of control, churning out ever more free radicals to damage the body at large.

Many research groups are working in this area - to better understanding the control mechanisms that lead to changes in your mitochondrial biochemistry over a lifetime, to validate the present Mitochondrial Free Radical Theory of Aging, and in some cases to target antioxidants to the mitochondria to extend life span by reducing the rate of damage. See these following posts for a sample of some of the present research in this area:


The SENS approach to eliminating the contribution of mitochondrial free radicals to aging is to copy fragile mitochondrial DNA into the well-protected cellular nucleus, thereby making damage to the actual mitochondria moot. See this next post for a step-by-step layman's explanation as to why this is so:


If we go hunting, we find that researchers are indeed working on moving mitochondrial DNA, albeit slowly and with only a little support:


Meanwhile, other groups with more funding are at hard at work on another potential repair strategy for damaged mitochondria - rather than moving mitochondrial DNA, it is apparently possible to replace it wholesale with fresh, new, undamaged DNA:


This is what good science looks like in a field still filled with a great many unanswered questions. You'll find overlapping research, different methodologies aimed at similar goals, and a large number of scientists producing results that confirm one another's work.


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!


Founder, Longevity Meme



To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

Exploring the Biochemistry of Klotho (March 04 2007)
I'm sure you recall news and discussion - back in late 2005 - of the effects of the klotho gene on longevity in mice: "Those mice proved to have life spans 20 percent or more longer than mice with the ordinary version of the gene ... The upper bound of life span extension in the study was 30% or so, in the same ballpark as the results of calorie restriction." Scientists are presently working on following the biochemical paths to understand how it works: "Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders ... Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered."

CALERIE Calorie Restriction Study Recruiting (March 04 2007)
2theadvocate.com notes that the CALERIE study of calorie restriction in humans is once more looking for volunteers: "Scientists at the Pennington Biomedical Research Center are looking for volunteers to figure out how cutting calories daily by 25 percent helps people live longer and healthier lives. A team led by Eric Ravussin recently found that cutting calories in an otherwise nutritious diet causes a slowdown of the aging process. Participants were also healthier, but Ravussin doesn't yet know what caused it. ... All participants in the calorie restriction study ate less and exercised more, so they also lost weight. We're not sure if their bodies reacted biologically to the decrease in calories or to the weight loss. That's what we're trying to learn now, but we need help. ... the clinical study requires participants to enroll in a 26-month trial. Pennington is looking for lean or slightly overweight volunteers who will eat either a restricted calorie diet or a normal diet. Both groups will also visit the center for a sophisticated series of tests to determine health status, metabolic rate, DNA damage and other measures." Find out how to enroll at the CALERIE website.

Reworking Humans For Longevity (March 03 2007)
An article at The Scientist is illustrative of the focus of that portion of the gerontology mainstream presently supporting healthy life extension: work to change human metabolism so as to slow the rate of degeneration. "In the absence of planned form and designed function, what we have is a living machine that appears well thought out, but which fails when operated beyond its biological warranty period. ... Anyone who understands how time takes its toll on the body and mind, however, will recognize that designing a human body built to last requires far more substantive changes than meddling with simple anatomy. So we've asked our experts to fiddle with physiology and tinker with the inner mechanics of life at its most basic biologic level. Although it is inevitable, for now, that all systems in the body experience some level of functional decline with the passage of time, not all components of the body degrade at the same rate. Furthermore, some structures are more vulnerable than others." And herein lies the problem - reengineering metabolism is an inefficient and difficult path in comparison to working to repair the damage of aging.

The Science of Cryonics (March 03 2007)
FirstScience looks at the present science behind cryonics: "cryonically preserving a body, or a brain, after death doesn't actually involve freezing - at least not anymore. The problem with freezing is that the structure and growth of ice crystals in cells is very damaging - anyone who has eaten dried-out food damaged by freezer burn has direct experience with the destructive effects of ice crystals. To avoid ice formation, cryonics has been moving towards a process called vitrification. To vitrify a body, a machine replaces blood with a solution containing a high concentration of chemicals called cryoprotectants that chill the body while preventing ice formation. ... The water molecules don't have time to form the rigid crystalline structure of ice, but instead maintain a fairly random arrangement that is referred to as a glass-like state. After vitrification, cryonics labs suspend people in liquid nitrogen at temperatures below -180 degrees C." Debates of the merits of the science usually devolve to "we can't restore cryopreserved people now," which rather misses the point. Our knowledge of physics and biochemistry show no roadblocks to the development of a future technology capable of restoring cryopreserved people - and they have all the time in the world to wait.

A Thought For the Day (March 02 2007)
Picking out the high notes from writer David Ewing Duncan at the MIT Technology Review: "You and I and our children may soon be living in a world where damaged hearts and shattered spines are routinely regenerated, or spare ones are regrown using stem cells; where a human egg containing a person's DNA can be engineered by adding and subtracting genes; where genetic fixes or perhaps a pill can be popped that extends lifespan, and keeps one young, fit and lean up to age 150, or longer. ... I believe this is the greatest story of our time, perhaps of all time. A species is developing the tools to redesign itself, to self-evolve in a way Charles Darwin never imagined." I can't say I agree with his message on the risks of progress, however. The greatest risk we face is the certain suffering, degeneration and death of billions should we fail to engineer greater and more rapid progress in the biotechnologies of longevity. What could be worse than everyone you know suffering and dying? Yet that is exactly what will happen if we don't get our act together.

Whose Life Is It Anyway? (March 02 2007)
Reason Online reminds us that government regulators of medical research and development are not our allies - their incentives are quite opposed to ours in the matter of health, responsibility and access to new medical technology. "Self defense is the most obvious and self-evident rights of men. No state can deny someone self-defense in the face of an attack. ... if the law recognizes that people have the right to defend themselves from attack by a bear or infectious bacteria, then surely they have the right to defend themselves against a rogue cancer cell. ... a patient who has exhausted standard treatments for some kind of severe disability, say, Parkinsonism, macular degeneration, or dementia, could argue that they have a right to access potentially better drugs that the FDA has not yet approved. ... Thousands died waiting for the FDA bureaucracy to let cancer drugs that would have lengthened and perhaps even saved their lives onto the market. Perhaps finding that mentally competent terminal cancer patients do have a fundamental right to access investigational drugs will finally spur the FDA to stop clinging to an outdated mid-20th century cancer clinical trial system and embrace one more suited to the 21st century science."

"What Have the Scientists Ever Done For Us?" (March 01 2007)
A reminder, from the Times, that it's often a hurdle even to obtain an acknowledgement of the value of medical science, let alone help to advance the cause of longevity research: "A recent [poll] found that less than half of people surveyed disagreed with the statement that 'the risks of science outweigh the benefits'. This is rather as if less than half of bodies believed that, on balance, the circulation of blood was a good thing. But this dismal statistic is perhaps not as surprising as it should be; for it is increasingly fashionable to assert that science is in trouble and that its troubles spell trouble for the human race. Scientific expertise and science itself are regarded with suspicion, while nonsense about science and nonsense passing itself off as science are given an easy ride. ... The figures on life expectancy are worth dwelling on: between the years 1800 and 2000, the worldwide average increased from less than 30 years to just under 67 years. ... None of this may cut much ice. Part of the problem is that the scientific basis of our current lengthened life and comfort span, and the huge enrichment of our lives, is rendered invisible through ubiquity."

RNA In Aging Research (March 01 2007)
Via EurekAlert and the Ellison Medical Foundation, a look at one small slice of the aging research community: "We found that genes that regulate the timing of events during C. elegans development also regulate timing of aging and death during adulthood ... Consistent with the lifespan analysis, mutants he studied were stress-sensitive and aged prematurely. Since some of these genes coded for small non-coding RNAs called microRNAs, his work provided some of the best evidence for a novel role for microRNAs in aging, and opened the potential of using microRNAs to regulate human health during aging. ... Our work has revealed unexpected connections between RNA misfolding, radiation damage repair and autoimmune disease. ... Damaged RNAs have often been detected in the brains of aging animals and patients with neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, because the cellular pathways for recognizing and degrading these RNAs are unknown, it has not been possible to determine whether RNA damage contributes to aging or to age-related diseases. ... Knowing how RNA damage contributes to aging or to neurodegeneration could be of broad importance for designing therapeutics that slow the aging process."

Lung Cells From Embryonic Stem Cells (February 28 2007)
Examples of continually improving control over stem cells have been rolling in of late; here is one from the University of Texas: "We have developed a reliable molecular procedure which facilitates, via genetic selection, the differentiation of human embryonic stem cells into an essentially pure population of lung epithelial cells ... the procedure also can be used to create other types of highly-specialized cells. ... The method involves the use of protein markers under the control of cell-specific promoters to convert undifferentiated human embryonic stem cells into highly-specialized cells. The human embryonic stem cells were cultured on specially coated dishes and transfected with a lung epithelial gene regulator of a drug selection gene. ... It is a general technology for developing select cells from human embryonic stem cells. The technology has allowed us to develop a platform that could potentially be useful in the development of spinal cord cells, heart cells, nerve cells and others. ... transplantable alveolar epithelial type II cells can be explored as treatments for pulmonary genetic diseases, acquired lung disease, as well as lung trauma caused by car accidents, gunshot wounds and sports injuries. ... These are the cells that can potentially be used for regenerative lung repair."

Continuing Explorations in Organ Regeneration (February 28 2007)
Exploration of the biochemistry of regeneration in lower animals is turning up interesting new information. From Nature: "Researchers have known for decades that an electrical current is created at the site of regenerating limbs. Furthermore, applying an external current speeds up the regeneration process, and drugs that block the current prevent regeneration. The electrical signals help to tell cells what type to grow into, how fast to grow, and where to position themselves in the new limb. ... the complex networks needed to construct a complicated organ or appendage are already genetically encoded in all of our cells - we needed them to develop those organs in the first place. ... The question is: how do you turn them back on? When you know the language that these cells use to tell each other what to do, you're a short step away from getting them to do that after an injury. ... The simplicity of the regeneration start signal is promising ... it is just possible that a properly tuned electric signal is all humans need to jumpstart tissue regeneration."

CIRM Legal Update (February 27 2007)
For those following along at home, another milestone in the legal battles over state-funded embryonic stem cell research in California is reported at TechNewsWorld: "The 1st District Court of Appeal upheld a decision by a lower court judge who last year ruled in favor of the California Institute for Regenerative Medicine, which was created when Proposition 71 was passed by 59 percent of the electorate in 2004. Opponents of the stem cell agency said after Monday's ruling that they likely would appeal to the state Supreme Court. ... Once again, the judiciary has upheld the constitutionality of California's innovative stem cell research project in its entirety, without equivocation, and with absolutely no room for further argument." Given the baseline motivation for the legal challenges - absolute opposition to embryonic stem cell research, as opposed to any of the specific fig leaves given by the legal folk - it seems unlikely this will be the last word. So long as they can raise funds and have an obvious next step, the anti-research opponents will continue working through the legal system.

Regeneration With Embryonic Stem Cells (February 27 2007)
Progress in using embryonic stem cells for regeneration is noted at EurekAlert!: "researchers have safely transplanted cardiac preprogrammed embryonic stem cells into diseased hearts of mice successfully regenerating infarcted heart muscle without precipitating the growth of a cancerous tumor - which, so far, has impeded successful translation into practice of embryonic stem cell research. ... Embryonic stem cells have the potential to become any cell type in the body. But directing the stem cells to regenerate targeted tissue is a process that hasn't yet been perfected. Scientists continue to closely scrutinize stem cell strategies to establish even safer and more effective treatments for disease. ... Embryonic stem cells are like a stealth fighter jet that flies virtually undetectable by radar. The host body doesn’t recognize embryonic stem cells, which it allows to multiply freely in an unimpeded fashion. ... The [study] is the first known report of a successful strategy for programming embryonic stem cells to suppress cancer genes, to mature into heart cells (also known as cardiomyocytes) and to successfully fix injured hearts without causing tumors to develop. The study removes a critical obstacle towards translation of regenerative technology into developing new therapies for people with heart disease."

More On Early Artificial Eye Development (February 26 2007)
Here is a general interest article from MSNBC on early work in the development of artifical eyes: researchers are "[researchers are] implanting special silicon chips in partially blind cats in a bid to help replace or possibly repair diseased retinas in humans. ... The chips, which provide their own energy, have shown encouraging results in clinical human trials, in some cases improving sight in people with retinitis pigmentosa or at least slowing the disease's development. ... Then there are the many attempts, like Optobionics, of creating artificial sight. Some efforts include miniature video cameras that pipe images straight to the brain, devices that send signals to a network of miniature electrodes attached to the retina or chips that eventually could graft themselves to retinal cells, creating a cyborglike system for producing images." The overlap between the development of prosthetics and regenerative medicine is particularly interesting: "A French company is conducting trials for an implant that would release proteins in the eyeball to offset the damage done to retinal cells, perhaps indefinitely."

Indefinite Life Extension Petition (February 26 2007)
The fellow behind the Coalition to Extend Life is looking for signatories for his online petition: "Our Declaration of Independence declares that, 'Life, liberty, and the pursuit of happiness' are inalienable rights for all people. Heretofore, life was a fixed period of time, which has steadily risen over the years. Recently, medical science has made amazing discoveries about how humans age and why they die. Many diseases are being conquered and our lives are being prolonged. The possibility of Indefinite Life Extension is on the horizon. No longer is an unrestricted lifespan an impossible dream, but many hurdles still remain. It is our position that Indefinite Life Extension be considered a national priority. In order to give full meaning to the right to 'life' we need a 'war on aging.' We ask you to create the conditions that will make this possible. First, a National Institute for Life Extension be created with sufficient revenues to fund research in this area. Second, that the Food and Drug Administration classify aging as a disease. Third, a National Commission be organized to study the social and economic impacts of this new reality. Fourth, a 'Manhattan Project' to cure the terminal disease of aging." I'm no fan of the enforcement of positive rights by government, as I'm sure you know, but you should feel free to do as your conscience directs.



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