Longevity Meme Newsletter, May 19 2008

May 19 2008

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.



- Things We Don't Need To Know To Cure Aging
- The Value of a Longevity Therapy
- Discussion
- Latest Healthy Life Extension Headlines


Functional bridges preceded the tools and understanding of modern architecture, just as beneficial medical techniques preceded the biotechnology revolution. More knowledge and science brings better bridges and more effective medicine - but you can still do good and save lives at earlier stages in the progression of knowledge.


"Is [a full understanding of our metabolic biochemistry] important and useful? Yes, of course, very much so. Is this knowledge necessary for us to proceed to reverse and repair aging? No. We already know what the damage of aging is, at the cellular and molecular level. Knowing more about the way in which that damage twists our metabolism and controlling biochemistry will help, in the same way that modern techniques of architecture improve bridge building, but the absence of that knowledge does not hold back significant advances in the engineering of healthy longevity.

"The only present barriers hindering rapid and aggressive progress towards rejuvenation of the aged are those of will and funding. That is why we can all help to make a difference to the future of aging science - you don't have to be a scientist to help make will and funding a reality."


What are people willing to pay for a medical therapy that is expected to add healthy years to life? Following that trail will give you a good idea as to how the development and commercialization of longevity therapies will proceed over the next few decades. As it happens, good research on the value placed on life already exists:


"Studies of real-world situations produce relatively consistent results, suggesting that average Americans value a year of life at $100,000 to $300,000 ... So let's take the hypothetical of a longevity therapy that the consensus believes will add ten healthy years to the average life. Replacing age-damaged mitochondrial DNA might do that in humans, for example. This suggests that to bring a first widespread commercial version to the high-end medical practices of the world, the price tag on the therapy has to be brought down below $1-3 million, or the value of a decade of healthy life."

That's the story for first few years of availability, of course, in which investors are recouping their initial investments, and before competition and refinement of the technology has started in earnest. The price will fall rapidly and quality increase as many more groups enter the market: competition is what drives the path to faster, better, cheaper.

"The stable state for a medical treatment is that in which many specialist staff are available, and a competitive marketplace exists to train those staff and supply needed raw materials. At that point, the cost is much the same for medical procedures across the tiers of specialist labor and complexity - it's largely down to the wages of those folk performing the work.

"Replacing mitochondrial DNA should be a hands-off outpatient procedure, once the technology is mature. Have a sample taken, send it off to the lab to work up a repaired genome and the viral vector, get injected with the vector that will replace your mitochondrial DNA with repaired versions, and then come back for regular testing for a couple of months. That is nowhere near as labor intensive as, say, heart surgery today. So one could look at comparable procedures that require supporting individual lab work on the back end, such as limited genetic testing, and take a stab at the price tag in the $10-30,000 range."

"That's a hundred times smaller than $1-3 million, which seems fair for the progression from early version to mature technology, especially in this age of rapidly advancing biotechnology. It's also a hundred-for-one bargain on the consensus expectation of value of life gained, which is a pretty good deal - good enough to tempt a very broad customer base, and enough profit for a large and competitive industry to form."

By way of a reminder, safe whole-body replacement of mitochondrial DNA was first demonstrated in laboratory animals three years ago:


Mitochondrial DNA damage is presently believed to be one of the more important root contributions to aging:


Funding and regulation are the highest barriers to developing a working mitochondrial replacement technology, gaining a consensus as to how much it will likely add to human lifespan, and bringing it to human trials over the next five to ten years.


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!




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/

Prototyping Artificial Cells (May 16 2008)
The first generation of mass-deployed medical microrobots is likely to consist of many different types of artificial cell, designed and grown to perform specific tasks in the body. As ScienceDaily notes, scientists are already making inroads into the basic tools and techniques: "researchers has developed a simple artificial cell with which to investigate the organization and function of two of the most basic cell components: the cell membrane and the cytoplasm - the gelatinous fluid that surrounds the structures in living cells. ... Many scientists are trying to understand cells by turning off genes, one at a time, and are observing the effects on cell function, but we're doing the opposite. We're starting from scratch, adding in components to find out what is needed to simulate the most basic cell functions. Our goal is to find out how much complexity can be observed in very simple collections of molecules. ... By creating a model cytoplasm with different compositions, we demonstrated that we can control the behavior of cell membranes. Now we want to find out what will happen if, for example, we add an enzyme whose activity depends on the compositions of the cytoplasm and cell membrane."

Surveying Ageing Research (May 16 2008)
Chris Patil of Ouroboros recommends we take the time to look through the ongoing review of aging science at Ageing Research, "a blog for those interested in learning more about the ageing process, specifically concentrating on cellular senescence and it's impact on age-related tissue dysfunction and disease development/progression." Patil suggests starting with the posts on what we know of cellular senescence: "I'm going to beseech the readers to check out the ongoing series on cellular senescence over at Ageing Research. Dominick has now turned to the relationship between senescence and human disease states, focusing first on atherosclerosis and vascular calcification ... For those of us working on senescence, Dominick's ambitious and thus far unflagging efforts to review the entire field are sure to generate a gold mine, and perhaps the gold standard online reference on this subject."

An Update on Bladder Regeneration (May 15 2008)
It sounds like preclinical work is proceeding well at Tengion: "Growing a replacement organ for a patient using his or her own cells presents a new option. After a bladder biopsy is obtained from a patient, bladder progenitor cells are grown in culture and seeded on a biodegradable bladder-shaped scaffold made from collagen and/or polyglycolic acid. The neo-organ is then implanted into the patient. The neo-organ is then implanted into the patient. Fourteen large mammals [were] implanted with the neo-bladder construct and within six months, structure and pharmacological characteristics of the neo-bladder were similar to the native bladder. There was no evidence of abnormal tissue development, immune response or evidence of systemic response to the neo-bladder regeneration. Results suggest that the new organ had successfully and safely regenerated. ... This treatment option essentially regenerates the patient's own bladder, reducing the risk of rejection and the need for immunosuppressant drugs. If successful in human clinical trials, patients should expect to regenerate normal bladder structure and function."

AGEs, RAGE and Diabetes (May 15 2008)
More reasons to spur the development of effective AGE-breaker therapies in this paper: "Non-enzymatic modification of proteins by reducing sugars, a process that is also known as Maillard reaction, leads to the formation of advanced glycation end products (AGEs) in vivo. There is a growing body of evidence that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerated rate under diabetes, thus being involved in the pathogenesis of diabetic vascular complications. Further, recently, engagement of their receptor, RAGE with AGEs is shown to activate its down-stream signaling and evoke oxidative stress and inflammation in diabetes. Since oxidative stress generation and inflammation are closely associated with insulin resistance as well, it is conceivable that the AGEs-RAGE system could play a role in the pathogenesis of insulin resistance and subsequently the development of diabetes." All this could be prevented or fixed if we just had periodic applications of a therapy to break down the major types of AGE.

Bone From Embryonic Stem Cells (May 14 2008)
A glance at ongoing progress in control over cells and tissue via ScienceDaily: researchers "break new ground by successfully creating bone tissue 'in vivo', using embryonic stem cells. They imitated bone formation in embryos and children, which uses cartilage as a template. ... While searching for a suitable scaffold to use for cartilage tissue engineering with mouse embryonic stem cells, the researchers selected a ceramic material that is often used as bone void filler. Other materials appeared to be unsuitable or they made it difficult to locate the implanted cells. In the lab, mouse embryonic stem cells were seeded onto this ceramic material and induced into the developmental pathway leading to cartilage formation. ... a scaffold with cells that had already formed cartilage, was implanted into a rat with a defect in its skull. Besides under the skin, bone was also formed in this bone defect. Therefore, this approach seems to be a promising new technique for repairing damaged bone."

Comparing Calorie Restriction and Exercise (May 14 2008)
ScienceDaily looks at the beneficial effects and mechanisms of calorie restriction and exercise: "We know that being lean rather than obese is protective from many diseases, but key rodent studies tell us that being lean from eating less, as opposed to exercising more, has greater benefit for living longer. This study was designed to understand better why that is ... Rats that exercise regularly will, on average, live longer compared to a group that eats the same amount but does not exercise. This is because exercise prevents some diseases, which allows more individual animals to live out their expected life span. However, when comparing the rats in these two groups that eat the same amount, the longest-lived animals in the exercise group don't live any longer than the longest-lived rats in the non-exercise group. Taken together, these findings indicate that exercise can prevent an early death from disease in some rats, but does not extend the maximal lifespan of any of the rats." The obvious choice for we humans is to both exercise and practice calorie restriction, obtaining all the benefits of both.

Thoughts On Aging (May 13 2008)
From "an open source mind blog": "Aging isn't a roadblock created by one inefficient system in the body. No system of the body had [evolutionary] pressure to create a perpetual repair mechanism and so every system of the body decays. ... Any individual that spent energy on repair would have been more likely to have been eaten by a saber tooth tiger or stomped by a mammoth. Modern life spans, then, are a function of historical danger. ... We don't age because its advantageous or nature wills it. Its simply because nature, until now, had no reason to do anything about it. Today, however, scientists are taking charge and developing the ability to increase human life span exponentially. Researchers like Aubrey De Grey are finally looking at aging as a very serious problem instead of an inevitability. That we can postpone aging is certain. The speed at which we develop these technologies, however, will depend on how quickly universities, scientists, funding boards, and the public adopt this same view on aging."

On Gerontologiphobia (May 13 2008)
Via In Search of Enlightenment: "There is an irrational public predisposition to regard research on specific late-life diseases as marvelous but to regard research on aging, and thus all late-life diseases together, as a public menace bound to produce a world filled with nonproductive, chronically disabled, unhappy senior citizens consuming more resources than they produce. No one who speaks in public about longevity research goes very far before encountering the widespread belief that research on extending the life span is unethical, because it will create a world with too many old people and not enough room for young folks. ... our attitudes towards aging and the science of longevity could stifle one of the most significant medical breakthroughs we could make this century. Retarding aging would significantly improve the health prospects of all persons." The Tithonus Error and knee-jerk Malthusianism remain large hurdles for healthy life extension advocates to overcome, despite the progress of recent years. Enhanced longevity will be enhanced healthy longevity, and advancing technology and free markets ensure there is more than enough room and resources for everyone.

The Argument to Moderation (May 12 2008)
The argument to moderation says, more or less, that you'll get more funding for longevity science if you stop talking about the logical result of successful longevity science - thousand year life spans and such. An example of the type can be found at Amor Mundi by way of the author's dislike for goal-oriented futurism above a certain threshold of ambition: "It seems to me that the resistance to de Grey's SENS research program and its 'engineering' focus [in] some quarters of biogerontological orthodoxy looks to be pretty well described in [terms] of incumbent resistance to a possibly promising scientific paradigm shift. ... at the level of rhetoric it seems to me were one to embrace the more 'bioconservative' [ideal] of a medical practice that would confer on everybody on earth a healthy three-score and ten years or even the 120-years some lucky few humans may have enjoyed this would be little distinguishable in the therapeutic effects it would actually likely facilitate (as a spur to funding, research, improvement of tools and techniques, theoretical publications, and so on) from those facilitated by the more 'transhumanist' ideal of technological immortality." I couldn't disagree more - progress in advocacy is achieved by pushing the boundaries of discussion as far out as possible. The further they go, the further goes the reasonable centerpoint.

The Nonsense of "Human Dignity" (May 12 2008)
"Human dignity" is a keyphase used by conservative bioethicists to justify relinquishing progress in longevity science - to permit the preventable death and suffering of billions to continue in the decades ahead. It is also nonsense in this context: "The problem is that 'dignity' is a squishy, subjective notion, hardly up to the heavyweight moral demands assigned to it. The bioethicist Ruth Macklin, who had been fed up with loose talk about dignity intended to squelch research and therapy, threw down the gauntlet in a 2003 editorial, 'Dignity Is a Useless Concept.' Macklin argued that bioethics has done just fine with the principle of personal autonomy - the idea that, because all humans have the same minimum capacity to suffer, prosper, reason, and choose, no human has the right to impinge on the life, body, or freedom of another. This is why informed consent serves as the bedrock of ethical research and practice, and it clearly rules out the kinds of abuses that led to the birth of bioethics in the first place ... [but] this government-sponsored bioethics does not want medical practice to maximize health and flourishing; it considers that quest to be a bad thing, not a good thing."



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