The are two paths ahead to the future of medicine. The high path sees rapid, growing, unfettered progress towards new knowledge and biotechnologies capable of curing all disease and reversing age-related damage. The low path leads to stagnation, progress spurned, opportunities squandered and suffering and death for all.

We are presently heading for the low path, thanks to ignorance, short-term greed and the rule of regulation, politicians and bureaucrats. Your prospects for future health and longevity are being squashed and wasted away; present legal and regulatory systems hand control of your well-being to people who don't care for you one way or another, and are in no way incentivized to help you.

How Government Medicine Really Works - British Edition:

Now the NHS wants to limit access to various drugs for Alzheimer's disease patients on the grounds that they are not cost-effective. Actually, there is a lot of research that suggests that delaying the cognitive decline that comes with Alzheimer's saves money because it delays much more costly care, such as admission to assisted living facilities. In any case, the NHS is engaged in pure and simple rationing.

Proponents of government health insurance will reply that private insurers might not cover the cost of such drugs and besides don't you know that there are 40, 50, or 60 million Americans without health insurance, so they wouldn't get the drugs anyway. So what? That response amounts to little more than that we should all get the same equally crappy care by government fiat. Just because extensive government meddling has screwed up private medicine in the United States surely doesn't mean that the solution to the problem is more government intervention.

Creating a commons - such as a socialized medical system in which no-one is permitted to make their own decisions about the deployment of their own resources, but rather everything is pooled at the whim of unskilled government employees - will always result in a tragedy. Here, the tragedy proceeds as rationing, waste, suffering and death - all of which are avoidable.

The US medical system is already two of three steps down this sorrowful road, and we all suffer for it already. Writ large, decades more of this will destroy any hope you and I have of a medical research and technology infrastructure rising to the level of defeating aging in our lifetimes.

Technorati tags: libertarian, medical research, politics, regulation

Posted by Reason at 11:05 PM
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If I'm going to discuss the future power-house technology of RNA interference (RNAi) in the context of fighting cancer, I should probably also mention closely related research into antisense RNA therapies - so says Charles Dorman in an email:

You've mentioned RNAi to cure cancer. Maybe I just missed it, but I haven't seen you mention [antisense RNA (aRNA)] applied to cancer. These articles are old, but this company has gotten its glioma drug through Phase III trials and has many more in the pipeline:

http://www.biospace.com/news_story.aspx?StoryID=19879020&full=1
http://www.engelpub.com/News/index.cfm?articleid=342460&categoryid=21

The results of its Phase IIb glioma trial was that 72 of 75 patients taking their drug were still alive at the time that the whole control group had died -- achieved essentially without side effects.

Both antisense and RNAi therapies are - comparatively speaking, at least in comparison to other technologies readily available today - precision methods of silencing the expression of particular problem genes. This could be thought of as a very limited way of reprogramming the biochemical engine in the nucleus of your cells.

One could say an antisense therapy is more of less half of an RNAi therapy, a comment that makes much more sense after reading this article:

When antisense RNA (aRNA) is introduced into a cell, it binds to the already present sense RNA to inhibit gene expression. So what would happen if sense RNA is prepared and introduced into the cell? Since two strands of sense RNA do not bind to each other, it is logical to think that nothing would happen with additional sense RNA, but in fact, the opposite happens! The new sense RNA suppresses gene expression, similar to aRNA. While this may seem like a contradiction, it can be easily resolved by further examination. The cause is rooted in the prepared sense RNA. It turns out that preparations of sense RNA actually contain contaminating strands of antisense RNA. The sense and antisense strands bind to each other, forming a helix. This double helix is the actual suppressor of its corresponding gene. The suppression of a gene by its corresponding double stranded RNA is called RNA interference (RNAi), or post-transcriptional gene silencing (PTGS). The gene suppression by aRNA is likely also due to the formation of an RNA double helix, in this case formed by the sense RNA of the cell and the introduced antisense RNA.

The Wikipedia entry might be a more gentle introduction:

Antisense therapy is a theoretical form of treatment for genetic disorders. When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid (DNA, RNA or a chemical analogue) that will bind to the messenger RNA produced by that gene, effectively turning that gene "off".

This synthesized nucleic acid is termed an "anti-sense" oligo because its base sequence is complementary to the gene's messenger RNA (mRNA), which is called the "sense" sequence (so that a sense segment of mRNA " 5'-AAGGUC-3' " would be blocked by the anti-sense mRNA segment " 3'-UUCCAG-5' ").

In essence, you can accomplish a great deal by interfering in the messenger RNA that genes use to accomplish their job of creating proteins. The comments I made in relation to the future of RNA intereference apply just as much here.

Cancer must be dealt with if we are to enjoy much longer, healthier lives, but let's tie this to another topic of great interest to those who follow healthy life extension research. You may recall that researchers have recently discovered that the Lamin-A mutations underlying the accelerated aging of progeria - mutations that lead to malformed cell nuclei and resultant failure of function - are also a part of "normal" aging:

In cells taken from the elderly, the nuclei tend to be wrinkled up, the DNA accumulates damage, and the levels of some proteins that package up DNA go askew ... The team suggests that healthy cells always make a trace amount of an aberrant form of lamin A protein, but that young cells can sense and eliminate it. Elderly cells, it seems, cannot. Critically, blocking production of this deviant protein corrected all the problems with the nucleus. ... You can take these old cells and make them young again.

So then, there is the possibility that any successful therapy for progeria will also be of use to repair these age-related cellular defects. At PubMed, we can find a full text paper reporting on research using antisense RNA technologies:

The fact that the antisense [RNA] reduced prelamin A levels in cells and improved nuclear shape is exciting, raising the possibility that systemic administration of these antisense compounds might ameliorate disease phenotypes in Zmpste24–/- mice or newly created mice with a targeted “Hutchinson-Gilford” mutation in [Lamin-A].

The next ten years in applied genetics are going to be most interesting.

Technorati tags: biotechnology, medical research

Posted by Reason at 9:34 PM
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In a recent LiveScience article on Aubrey de Grey, the MPrize for anti-aging research and the SENS Challenge, Methuselah Foundation co-founder Dave Gobel neatly encapsulated the reason behind a prominent quirk in the MPrize structure.

The MPrize has been divided into two prizes since launch in 2003; the names have changed with time, but they are presently known as the Longevity and Rejuvenation prizes.

A fund exists to provide the money for the Longevity and Rejuvenation prizes. This fund is open to contributions from anyone; donors can contribute to either or both prizes as they see fit.

...

The Longevity Prize is won whenever the world record lifespan for a mouse of the species most commonly used in scientific work, Mus musculus, is exceeded. The amount won by a winner of the Longevity Prize is in proportion to the size of the fund at that time, but also in proportion to the margin by which the previous record is broken.

...

The Rejuvenation Prize rewards successful late-onset interventions and has been instituted so as to satisfy two shortcomings of the Longevity Prize: first, that it is of limited scientific value to focus on a single mouse (a statistical outlier), and second, that the most important end goal is to promote the development of interventions to restore youthful physiology, not merely to extend life.

Donors have always had the free choice of which prize to bolster. Without any prompting from the organizers and volunteers, the vast majority of donated funds have been applied to the Rejuvenation Prize. Dave Gobel sums up why this is so:

People who happen to be alive want to be fixed.

Technorati tags: life extension, MPrize

Posted by Reason at 11:23 AM
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Why do some people vociferously oppose the idea of living a longer, healthier life? Some thoughts via sci.life-extension:

Somewhere along the line and very early on, we self-conscious creatures made some inevitable observations about our existence. It is painful to come in to, for both mother and child, and it is generally painful to leave (and can take a long and torturous time), for the individual and everyone else who's left.

...

Since there seemed to be so little (if anything) we could do about it, we mistakenly concluded that this was all somehow our own fault, a punishment inflicted upon us by some creator(s) for something very bad that we had done a long time ago. Accepting this as fact then became a societal imperative, and a sign of having achieved adulthood, maturity, a cold and realistic view of the "nature" of life on this planet. Accepting this view then became a point of pride.

The very prospect, the mere suggestion, of the extension of the human lifespan on a scale that Aubrey de Grey says is possible and worth persuing results in reactions from some people which reveal how deeply they actually loath themselves, their own lives, and the rest of humanity as a whole. This is one profound reason for the vociferous objections to de Grey's ideas.

The reactions of Nuland, Pontin, Hayflick, and countless others, reveal such individuals for what they really are: people acting upon a fundamental, archaic self-loathing that they have accepted, and consider part of their virtue, experience, and expertise.

I don't think self-loathing or a distaste for aspects of life has to be particularly archaic or Jungian to provide the basis for opposition to healthy life extension. Plain old misanthropy or the lessons learned from a catalogue of unfortunate experiences probably serves just as well for some. While people grow and change continuously from day to day and year to year - and usually for the better - it is often hard to see a better future from a position of misery. Strong religious beliefs are another common root; people may like life, but like the idea of what they believe comes after death even more. That the grass is greener on the other side is a hardwired trait for us primates; a pity it supports things like this in addition to more beneficial practices.

Whatever our varied opinions, whatever the contribution of our genes and personal history, ultimately it is - and should be - the choice of the individual as to whether to extend his or her healthy life span. Respect that choice and others will be much more likely to respect yours. The people who should be stepped on, and with great vigor, are those who extend their opposition to block your freedom to attempt to live a longer, healthier life. Where I come from, we call that murder - it may take longer than more traditional methods, but the end result is just the same.

Healthy life extension is, at the most fundamental level, all about choice. Specifically, it is a matter of engineering a choice that cannot presently be made. We are attempting to create a new freedom; the freedom from age-related suffering and death for as many as choose to work towards that goal.

Moving on from the self-loathing a little, why do those folk who stand in opposition to longer, healthier lives receive so much press? What is the fascination with people who want to die, versus those of us who want to live in good health? Is this simply another aspect of "good news is no news?" Or perhaps it is a modern outlet for the hardwired impulses that lead to death worship and other mystery cults; a facet of the curiosity over people who do bad things to themselves, or those who "explore" (and I use that word advisedly, since all who go there cease to exist) what some people will always regard as the unknown.

Take this Cosmic Log entry at MSNBC, for example, which follows up on the trail of anti-life-extension LiveScience articles (first, second and third) from the past week:

This week, a series of stories from LiveScience laid out the potential problems with immortality - or, more realistically, medical advances that could extend normal life spans well beyond the 100-year mark.

The typical response from MSNBC.com users shouldn't come as a surprise: We should all have such problems. But the dissenting opinions were, if anything, more interesting.

In a world in which we have moved quite rapidly in the past five years from healthy life extension in the fringes to the typical response to negative articles on healthy life extension being "let's get out there and do it," why does this fixation with the pro-death and suffering camp exist?

Technorati tags: death, life extension

Posted by Reason at 1:27 PM
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While browsing sci.life-extension, I noticed two papers on calorie restriction (CR) that you might find interesting. Scientists are increasing our understanding of the mechanisms by which a calorie restricted diet brings impressive health benefits - and extended healthy and maximum life spans in most species - much more rapidly in this decade than the last. Perhaps this has as much to do with growing numbers of higher mammal and human studies as with the relentless advance of biotechnology.

Effects of caloric restriction are species-specific:

This article addresses two questions: (1) 'can caloric restriction (CR) extend the life spans of all species of experimental animals', and (2) 'is CR likely to slow the human aging process and/or extend the human life span?' The answer to the first question is clearly 'no', because CR decreases the life span of the housefly, Musca domestica, and fails to extend the life span of at least one mouse strain. The answer to the second question is unknown, because human CR has not yet been shown either to increase or curtail the human life span. However, recent efforts to develop insect models of CR have been unsuccessful and/or relatively uninformative, so any insights regarding the relationship between CR and human aging are more likely to arise from studies of established, mammalian models of CR.

I think that the health benefits of human CR (in terms of resistance to age-related disease) are in the proven box now, with open questions regarding which populations benefit most or least. Life span effects seem probable, if only from a consideration of the reliability theory of aging. If you use CR to reduce cellular damage at the root of - or resulting from - age-related diseases, and aging is just an accumulation of this damage, then you should be slowing aging.

A few intriguing studies on inadvertent CR and human life span exist, as well as a number of scientific arguments against significant gains in maximum life span in humans, but nothing conclusive as yet. Don't expect "conclusive" to arrive any time soon either - for all of modern biotechnology, we're still stuck with extrapolation based on prevention of age-related disease, or waiting for people to die and counting the years. With that cheerful thought in mind, onto the next paper.

Effect of Long-term Calorie Restriction with Adequate Protein and Micronutrients on Thyroid Hormones:

Calorie restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in triiodothyronine (T3) hormone may increase lifespan by conserving energy and reducing free-radical production.

...

low serum T3 concentration was not associated with an increase in inflammatory cytokines in our CR subjects. In fact, markers of systemic inflammation, serum CRP and TNF-α concentrations, were low in our CR subjects. These findings are consistent with data from CR studies conducted in rodents and monkeys, which showed that CR caused a marked decrease in markers of inflammation and a reduction in serum T3 concentration. The combination of decreased serum T3 and reduced systemic inflammation could alter the aging process by reducing metabolic rate, oxidative stress and systemic inflammation

...

Long-term CR with adequate protein and micronutrient intake in lean and weight-stable healthy humans is associated with a sustained reduction in serum T3 concentration, similar to that found in CR rodents and monkeys. This effect is likely due to CR itself, rather than to a decrease in body fat mass, and could be involved in slowing the rate of aging.

The full PDF version of this paper is available. This human study confirms an observation of one distinct effect of CR in other mammals; this is now a more viable mechanism for further investigation, especially since the researchers seem to have eliminated the weight loss that accompanies CR as a possible cause. I find the reduced markers for inflammation more interesting than T3 levels, though that may be a bias resulting from the past few months of news on that topic - chronic inflammation is quite the bugbear in terms of its long-term effects on your health.

Clearly, calorie restriction is accomplishing a range of beneficial changes to biological processes across the board. Good stuff.

Technorati tags: aging, calorie restriction, health, life extension

Posted by Reason at 5:08 PM
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Leonid Gavrilov just recently pointed out the hefty Handbook of Models for Human Aging It's also on Amazon if you're interested in a less hefty price tag.

This Handbook is designed as the only comprehensive work available that covers the diversity of aging models currently available. For each animal model, it presents key aspects of biology, nutrition, factors affecting life span, methods of age determination, use in research, and disadvantages/advantes of use. Chapters on comparative models take a broad sweep of age-related diseases, from Alzheimer's to joint disease, cataracts, cancer, and obesity. In addition, there is an historical overview and discussion of model availability, key methods, and ethical issues.

...

Readership: Researchers interested in the mechanisms of aging, gerontologists, health professionals, and allied health professionals and students

The index of contents certainly reads like a who's who for half of modern gerontology. Some of what caught my eye:

2. Species Selection in Comparative Studies of Aging and Anti-Aging
Joao Pedro de Magalhaes

5. Models of Systems Failure in Aging
Leonid A Gavrilov, Natalia S. Gavrilova

17. Telomeres and Aging in the Yeast Model System
Kurt W Runge

20. Strongyloides Ratti: A Nematode with Extraordinary Plasticity in Aging
Michael P. Gardner, David Gems, Mark Viney

34. Life Extension in the Dwarf Mouse
Andrzej Bartke

41. Mitochondrial DNA and Aging
Mikhail Alexeyev, Susan P. LeDoux, Glen L. Wilson

45. Therapeutic Potential of Stem Cells In Aging Related Diseases
Shannon Whirledge, Kirk C.L. Lo, and Dolores J. Lamb

66. Human T Cell Clones in Long-term Culture as Models for the Impact of Chronic Antigenic Stress in Aging
Graham Pawelec, Erminia Mariani, Rafael Solana, Rosalyn Forsey, Anis Larbi, Simone Neri, Olga Dela Rosa, Yvonne Barnett, Jon Tolson, Tamas Fulop

80. Werner Syndrome as a Model of Human Aging
Raymond J Monnat, Jr

A thought: if you can reasonably claim to cover the diversity of scientific approaches to aging - we'll take it that the diversity of experimental classes (or models) scales with the diversity of the science - in one fairly hefty book, that seems to be to indicate that nowhere near enough resources are presently focused on this very complex topic. I don't believe one could adequately tour models for cancer research in 1075 pages, for example. That's something to think about when looking at what must be done to ensure a future of large-scale, effective, well-supported longevity research.

Technorati tags: aging, books, gerontology, medical research

Posted by Reason at 10:10 PM
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It's easy to draw parallels between work on RNA interference (RNAi) today and gene therapy circa 1986. Both have demonstrated tremendous potential as platforms for building therapies to treat - or cure - a wide range of conditions that presently lack effective therapies. Both are powerful tools for changing our genes and biochemistry; a comparative lack of understanding can harm the recipients of therapies:

Long-term use of RNA interference (RNAi) can be fatal in mice, scientists report in this week's Nature. However, some short hairpin RNAs (shRNAs) suppressed viral infections without killing the mice, suggesting that the technology may still be useful -- if used carefully.

...

Irvin Chen at the University of California at Los Angeles, also not a co-author, noted he also has found that some shRNAs directed against CCR5 for HIV-1 therapy proved toxic with long-term use in primary human T-cells and chimeric mice, while other shRNAs were not toxic in the same setting. "The more data we accumulate about what shRNAs and siRNAs are and are not toxic, the better we can get at the mechanisms and in the future hopefully be able to predict toxicity," he said.

Much the same was said about gene therapy in its infancy, and rightfully so. These are some of the most challenging areas of modern biotechnology - but then building powered aircraft that could actually fly was challenging a century ago. The challenges of the present day are the foundations of medicine far more capable than most researchers envisage.

Gene therapy has advanced greatly in the past 20 years - dozens of clinical trials are presently underway or in planning. RNAi medicine will advance more rapidly, as today's enabling biotechnology is (quite literally) a thousand times more capable than that of 1986. Still, the human factor is the eternal sticking point; no matter how powerful your bioinformatics, it still takes much the same time to sort out funding, organize research efforts, fill out paperwork, pay a cut to government wastrels, and so forth.

A central target for RNAi research - and much gene therapy research for that matter - is cancer:

RNAi Versus Cancer:

RNAi is so new only three companies are experimenting with drugs based on it, but none are targeting cancer. Unlike other drugs on the market, SanoGene's experimental drug targets multiple cell origins of brain tumors, blocking the invasion of cells into other tissue. So far, it has shown extremely positive results for the drug in animal models, according to its founders

More RNAi Versus Cancer:

scientists were the first to use what are known as 'small interfering RNAs' to block the spread of human colorectal cancer cells implanted in laboratory mice. ... Over the last couple of years people have talked a lot about cell-culture studies of siRNAs, but only a handful of labs have pushed it to animal models, which we need to do before going on to clinical trials."

Revolution in the fight against cancer & viruses:

"We've exploited this process by creating short interfering RNA, or siRNA, that are being developed into drugs to fight viruses and cancer," he said. "We've now taken this a step further and worked out how we can create siRNA with different cellular properties to target different diseases."

...

"By 'tweaking' the structure of siRNA to target specific diseases, we can dictate whether we want a particular siRNA-based drug to block or promote an immune response, to increase the effectiveness of the treatment," he said. "While our research is at an early stage, human trials using siRNA are currently underway in the USA and Europe. We're confident our have a significant impact on the way siRNA is being developed as a weapon in the fight against viruses and cancer," said Professor Williams.

Medical revolutions tend to be slow-burning affairs of a decade or more - but RNAi will be the next gene therapy, I'll wager. Ten years from now, there will be dozens of trials, just as for gene therapy in the present day. Like gene therapy, RNAi is a powerful technology with great application to many age-related conditions - and ultimately to making adaptive alterations to human biochemistry to better withstand or repair the cellular damage at the root of aging.

Technorati tags: biotechnology, medical research

Posted by Reason at 8:58 PM
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Competition is good at all stages of the research pipeline; it's the alchemy by which base human fears and desires are transformed into technological progress and better lives. More competition means a greater chance of more efficient, effective new medical technologies; the more competition the better, I say.

One contest of note is that between the development of artificial replacements for body parts and the progression of tissue engineering (or regenerative medicine - the line blurs when the body parts under discussion are small, such as a handful of cells in the eye). Given equal funding and a standing start for research and commecialization, it seems plausible to imagine either a minaturized, implantable kidney-shaped lifetime dialysis machine or a fully functional kidney grown from your own cells arriving at the finish line first. We live in exciting times: the same advancing biotechnology that enables tissue engineering also makes it possible to replicate biological functions in other systems - and at ever smaller scales.

It's all in the early stages now when talking about recreating the functions of entire organs, of course. A good example of present day research cropped up in the MIT Technology Review recently:

There are several different approaches used today in the attempt to develop retinal prosthetics. But the basic principle underlying all of them is the same: by stimulating cells within the retina, vision sensations can be elicited in the visual cortex. This is possible because for some common eye diseases, like retinitis pigmentosa and macular degeneration, only the light-sensitive photoreceptor cells in the retina are damaged. This means other types of cells in the retina and visual cortex in the brain remain intact and fully functional.

Until now, the method of choice for repairing these cells has consisted of using arrays of electrodes placed near the retina to stimulate the cells electrically. The trouble with this technique is that, apart from the electrodes being larger than the cells they're trying to stimulate, there is no way to isolate the electric fields in order to trigger individual neurons without triggering their neighbors.

Encouraging the cells to grow tentacle-like dendrites between the cell and an electrode [gets] around this problem by creating a communication channel that stimulates the cell without invading or disrupting the structure of the retina.

The real payoff with this method, though, is the ability to make use of the preprocessing of the [retina]. Until now, most research has focused on stimulating the retinal ganglion cells, the large cells that feed signals directly into the optic nerve. But this bypasses all the motion-detection and edge-detection processing carried out in the retina itself by a network of neurons called bipolar cells.

My one complaint about all this is that, for all the rapid advance in capabilities, this type of work is directed at patching up the end results of age-related biochemical damage - plugging holes in the crumbling dam rather than preventing or repairing the root causes of those holes.

Technorati tags: biotechnology, medical research

Posted by Reason at 8:45 PM
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Lipofuscin is one of the many different types of extracellular aggregates that contribute to aspects of age-related degeneration. It's one of the targets for the LysoSENS work funded by the generous donors who have given to the Methuselah Foundation. LysoSENS is a bioremediation approach - we know that all this junk in and around our cells in ultimately digested by soil bacteria, so we should get out there and identify the enzymes involved. This is a big job, but more hands speed the work.

LysoSENS is not the only program looking into tackling the accumulation of toxic byproducts of our biochemistry. Most of the others are characterized by a focus on one particular disease and its associated intracellular or extracellular accumulations. Thus, back we come to lipofuscin, via a release at EurekAlert:

Harvard Medical School announced today that is has signed a multimillion-dollar license agreement with Merck & Co., Inc. to develop potential therapies for macular degeneration ... Under the terms of the agreement, Harvard will receive a $3 million up-front payment, significant milestone fees and downstream royalties on any marketed products that result from this agreement.

...

Dr. Rando's approach is to prevent toxic substances called lipofuscins from forming in the eye. "Lipofuscin accumulation appears to be a major risk factor for macular degeneration, including the age-related type," said Dr. Rando. Toxic constituents of lipofuscin are generated as byproducts of the visual cycle, a complex chemical pathway that is required for the maintenance of the light gathering components of the eye called retinal photoreceptors.

When light hits the retina, which is packed with photoreceptor cells, a complex chemical process occurs that stimulates the optic nerve. ... The most common by-products of the vision cycle comprise the lipofuscins, which are very stable toxic substances, and not readily eliminated from the eye.

...

One of the worrisome issues with the lipofuscins is that they are insoluble and form aggregates akin to plaques, suggested Dr. Rando. In addition, he noted the lipofuscins and their readily formed oxidation products are highly retinotoxic for a variety of reasons, which includes their propensity to react with DNA and other macromolecules.

...

Dr. Rando, members of his research team, and collaborators at Columbia University, selected small molecule antagonists that they had previously synthesized and showed that they can also stop production of the retinotoxic lipofuscins.

The more the merrier, and good luck to their team. As I've no doubt noted in the past, most of the seven pillars of Strategies for Engineered Negligible Senescence (SENS) are already engaged by the mainstream scientific community in connection with various age-related conditions. Progress towards lengthening the healthy human life span is being made, just not in a directed and efficient manner.

Technorati tags: aging, medical research, SENS

Posted by Reason at 10:08 PM
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I'm somewhat overdue in pointing out a piece by Natasha Vita-More entitled "The Strategic Sustainable Brain":

People are living longer; there is a notable increase in the number of activists supporting life extension technologies; economic reporting predicts an increase in research and development of molecular manufacturing and nanotechnology; programming engineers are reveling in the increase in research and development of superintelligence; and conservative organizations are publishing warnings indicating an increased awareness of the potential threats of superintelligence. These events will directly or indirectly affect the brain, resulting in a set of expectations for the brain to function over a longer period of time and operate at a higher level of quality than it has ever achieved in the past.

While I wouldn't have approached the topic in quite the same way, being more of a first things first type, I'm basically in agreement. It should be of interest to those of us looking at the long haul who are most concerned about neurodegeneration and the long term maintenance of the brain. You are your brain; the rest of your body could, at worst, be replaced via future regenerative medicine, but we will need to be very good at repairing the brain in situ - or building a better alternative.

Technorati tags: life extension

Posted by Reason at 11:22 PM
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Here are a few links of interest for you to peruse this Sunday; thanks go to the busy infomorphs of the sci.life-extension group for the first few. These folks perform a very useful service for the rest of us, taking their valuable time to sort through a great deal of data in search of connections and items of note.

Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan:

Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging.

The plasma membrane redox system in aging:

Oxidative stress over time leads to the accumulation of damaged macromolecules and to profound physiological changes that are associated with several age-related diseases. The plasma membrane redox system (PMRS) appears to attenuate oxidative stress acting as a compensatory mechanism during the aging process. The PMRS appears to play a protective role during mitochondrial dysfunction to provide cells with a survival mechanism by lowering oxidative stress.

Plasma membrane redox systems across various species form a big topic - big enough for their own conference. As you might note from the papers above, or indeed from pretty much anything I post here on the topic of mitochondria, metabolism is a fearsomely complex system. Greater understanding of the biochemistry of metabolism could lead to technologies of optimization - meaning least amount of age-related damage generated - that are demonstrably better than the practice of calorie restriction. Don't hold your breath there, however; this has the look of a topic that will still be hotly debated and the subject of ever-deeper investigation in 2016 and 2026. Meanwhile, calorie restriction is as simple a matter as putting thought into eating less in the right way. More to the point, tinkering with metabolic optimization seems to be a far less effective path forward than to aim at directly and effectively repairing what we know to be the root biochemical causes of aging.

To finish up, you'll find a set of sizeable videos of a Brian Wowk presentation on cryonics and vitrification in a thread over at the Immortality Institute.

Dr. Brian Wowk's presentation on Suspended Animation by Vitrification at the Life Extension Conference is now available ... It is recommended that you choose to "Save" the files rather than stream them online

Vitrification, as I've noted before, is a fascinating topic in and of itself. It shows potential to become the spin-off, revenue-generating infrastructure technology that the cryonics industry needs in order to support further growth. Alcor has been moving forward with this; a good thing in my book. If you're interested in learning more, one of the papers in the latest Rejuvenation Research was co-authored by Wowk:

Until recently, the cryopreservation of organs has seemed a remote prospect to most observers, but developments over the past few years are rapidly changing the scientific basis for preserving even the most difficult and delicate organs for unlimited periods of time. Animal intestines and ovaries have been frozen, thawed, and shown to function after transplantation, but the preservation of vital organs will most likely require vitrification. With vitrification, all ice formation is prevented and the organ is preserved in the glassy state below the glass transition temperature (TG). Vitrification has been successful for many tissues such as veins, arteries, cartilage, and heart valves, and success has even been claimed for whole ovaries. For vital organs, a significant recent milestone for vitrification has been the ability to routinely recover rabbit kidneys after cooling to a mean intrarenal temperature of about -45°C, as verified by life support function after transplantation. This temperature is not low enough for long-term banking, but research continues on preservation below -45°C, and some encouraging preliminary evidence has been obtained indicating that kidneys can support life after vitrification.

Technorati tags: aging, biotechnology, cryonics, medical research

Posted by Reason at 3:58 PM
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