There's nothing quite like putting your money where your mouth is. It's something that more advocates and volunteers supporting healthy life extension are going to have to do in order to accelerate progress in advocacy, education and public awareness. I'm very pleased to see this initiative on the part of Mark Patterson:

As most of you know I've founded Big Picture Tours for one reason: to fund rejuvenation research. For now, 100% of this focus translates to supporting the Mprize for rejuvenation and longevity research.

Big Picture Tours combines advanced Internet technologies with our own proprietary server-side ClientSmart(TM) technology to deliver bezel to bezel full-screen presentations of unmatched photographic quality. Our server side technology detects the client aspect ratio, connection speed and operating system and then streams a presentation (choosing among 18 versions) best suited for the client.

The result is that businesses and organizations are able to "tell their story" over the Internet in ways never before possible.

Some of you operate your own businesses and could benefit from this technology, others may work for businesses that could benefit. For the first twenty projects referred through contacts on the Mprize list or any Mprize 300 member, Big Picture Tours is offering to donate all revenues above our cost. This will translate to thousands of dollars donated directly to the Mprize. Please contact me at Mark@BigPictureTours.com for further details.

Below is a link to 4 of our recently completed projects so that you can see the quality of our work first hand. Once you've got a show running, right click and select "Full Screen".

http://www.BigPictureTours.com/GreatestHits.aspx

A very good job; that's something for the rest of us to top - and to spread the word about.

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Michael Shermer, Scientific American's skeptic-in-residence, has run off a rather sub-par column on Kurzweil and healthy life extension. While I have to agree with him on points relating to supplements and Kurzweil (see some of my previous thoughts, harsh and more forgiving), Shermer makes a number of pronouncements with no basis in anything other than his own opinions. For example:

Two, I question the idea of extrapolating trend lines very far into the future. Human history is highly nonlinear and unpredictable. Plus, in my opinion, the problems of creating artificial intelligence and halting aging are orders of magnitude harder than anyone has anticipated. Machine intelligence of a human nature could be a century away, and immortality is at least a millennium away, if not unattainable altogether.

Personally, I think it's amusing to see someone think that developing general artificial intelligence is 10 times easier than defeating aging! I think that Shermer would benefit greatly from reading the work of Aubrey de Grey, who makes a very compelling case that we a) know more than enough to get going now on serious anti-aging research and b) making meaningful progress in radical life extension is only a matter of a few decades with the right level of funding.

In addition, I don't think that Shermer grasps the concept of escape velocity in healthy life extension. Even if true physical immortality is a thousand years away - a highly unrealistic thing to say in and of itself - all ("all") we have to do to live that long is to keep adding new medical technologies to extend healthy life span, bit by bit, more rapidly than one year ever year. This is not an unreasonable goal - it is within the capabilities of a large, directed research community. Kurzweil is quite clear about this concept in his writing, and presents it as developing a series of bridges to the future.

The sort of knee-jerk, unfounded skepticism of the sort expressed by Shermer - and millions of other people who think the same way - is one of the many obstacles to widespread support for healthy life extension research. The future is not a conveyor belt, but rather something that is built, brick by brick, by the actions of people. The future is directed, open to change, a road that could go in any direction. Just because something could be done does not mean it will be done: without public support and understanding of healthy life extension and its potential, research will not be funded and science will not move ahead. Skepticism becomes a self-fulfilling prophecy - which may briefly satisfy some folks, but we'll all be just as dead because of it.

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A nice piece of news from Nature:

On 24 June, Kevin Eggan of the Harvard Stem Cell Institute told an international scientific meeting that his lab has fused a human embryonic stem cell to an adult skin cell. Eggan showed that the embryonic stem cell 'reprogrammed' the skin cell's nucleus, causing the skin cell to start behaving like a youthful, embryonic stem cell.

The fused cell can't be used for much - but it is a proof of principle for the future of tools that can change the state of cells. Our cells appear to be finite state machines on a level that scientists are beginning to be able to manipulate. Arrangements of genes and proteins determine how a cell behaves - whether it is a stem cell or a normal cell, for example. As biotechnology and medicine advances, scientists will be able to create stem cells - or any other type of cell required for regenerative therapies - as needed. This is a very worthwhile goal, the development of technologies to form a comprehensive biological repair kit capable of tackling a range of age-related disease and damage.

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There are no shortage of horrors in the world: famine, war, inhumanity and plague of a thousand stripes. It is human nature to hunch over and try to believe that it will never happen to us - those of us in the wealthy Western world might even be luckily correct in this belief. But degenerative aging - the result of accumulated, unrepaired damage to the complex machinery of our bodies - brings pain and suffering to best the most malignant disease. Do you think you know what lies ahead? Do you think you have come to terms with it? Read this harrowing account from See Spot CRON! ... read it all the way through. Those ugly details form the future that awaits everyone who is reading this now.

Without action now, your future will be one of pain and suffering, of the slow destruction of your body and mind. Aging is not noble. It is not romantic. It is a slow and increasingly terrible disease - no one goes quietly or with dignity.

But still, we do our best to put this out of our minds. Human nature at work. Yet there is hope - medical science is within decades of developing therapies to prevent and repair the root causes of age-related degeneration. However, the funding to make these therapies a reality will only be deployed in a climate of widespread support for rejuvenation and understanding of the possibilities. It is a matter of will and resources rather than a matter of science - the technological and medical path ahead is clear. The path of fundraising and awareness is not.

By refusing to face an unpleasant future, and thus failing to take the actions that could have saved us, we will doom ourselves to the very thing we feared to confront. We can do better. We can face the realities of aging and do something to make a difference - each and every one of us. The alternative is not pretty.

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A post from Frank at Anti-Aging Science & Medicine (commenting on some nice simulational biotech work at HHMI) made me think again about just how open source development methologies and cultures will shape the future of biotechnology.

What are the implications for garage biotechnology hacking? If bioinformatics was the sole technique, it would seem that anyone could have done this research in their garage with computer access to the genomics database and some know-how. My point is not to downplay the scientist's work but to present the possibilities for the amateur scientist in the light of "open source biotechnology".

Know-how is expensive, of course, but not as expensive as you might think. If the cost of entry is low (a low cost, high power computer, some general smarts, an investment of time) then someone with 1/10 of a high-level professional biotech know-how can produce useful results at 1/10 of the rate and effectiveness of the professionals. If they mess up, then they mess up - in simulation rather than with real genes in real organisms. Experimentation and diversity will be the order of the day when the only cost is the time of dedicated citizen scientists and the only downside is that some of that time will be wasted. Useful progress may be slow for each individual, but many, many people will be qualified to participate.

As I pointed out previously, this breaking down of the priesthood through lowered barriers to entry is how open source development has greatly advanced software development. It will do the same for biotechnology - hard problems requiring large investments in knowledge and resources will still typically be solved by scientific professionals working in traditional organizations, but they won't waste their time working on the easier issues. The much larger number of citizen scientists will be rapidly organizing to accomplish everything they are capable of and freely sharing the results of their work.

One benefit that truly stands out in this future is that research projects ignored by mainstream funding organizations stand a strong chance of making headway. One such presently ignored project is serious anti-aging research, work to find ways to prevent and reverse age-related damage - and soon. As biotech advances and computers become more capable, we activists are going to move from talking, educating and raising money to all that plus performing scientific research using the tools of open source biotechnology.

This is still some years ahead, however - the first generation tools, standards and platforms are still under evolving and under construction. See for example, to pick two quick, illustrative organizations at random, BIOS and the Open Bioinformatics Foundation. This process will accelerate the further it goes, and a large number of smart people are working on it. It's a bright future if the history of software development to date is anything to go by.

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If you haven't dropped by the Mprize website recently, you sould certainly do so.

The Methuselah Mouse Prize is the premiere effort of The Methuselah Foundation; a scientific competition designed to draw attention to the ability of new technologies to slow and even reverse the damage of the aging process, preserving health and wisdom in a world that sorely needs it.

The pledge total for the Rejuvenation and Longevity research prize fund has passed $1.3 million, and more than 50 people are now members of The Three Hundred organization. The number of endorsing organizations continues to grow and the news articles roll in. In short, things are moving forward; good progress is being made thanks to the many generous donors and volunteers who have stepped forward to date. Reinforce success in advocacy for the fight to cure aging and make your pledge today!

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While wandering the wilds of the world wide web, I noticed that InfoAging (a very useful online project funded by the American Federation for Aging Research) updated their section on mitochondria and age-related degeneration just a few months ago.

Mitochondria are the cells' energy converters. We need them to transform nutrients into the energy we need to live. Mitochondria also produce damaging oxidants—free radical molecules produced by the metabolism of oxygen—that can wreak havoc on cells and their DNA. As the source of these toxic products, mitochondria are also their first potential victims. Their proximity to the free radicals they produce, combined with their exceedingly intricate structure, make them particularly vulnerable to injury over time. Not surprisingly, researchers are seeking to understand this injury as a critical part of the aging process, and perhaps a cause of a host of age-related diseases.

Since InfoAging is an excellent resource for the layman who wants to know about current aging research and the conservative scientific consensus on aging, and since I've been talking about mitochondrial research of late, I thought I would point this out.

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No, really, how much would you pay to live forever?

Think of it this way: What is your willingness to pay to live forever? I'd happily pay all my earnings in excess of $10,000 in perpetuity - a present value of millions of dollars.

OK, but what is your willingness to pay for a bottle of medicine that a spammer says will let you live forever? I wouldn't pay a penny.

Are doctors no more credible than spammers? That's going too far. But the bottom line is that life is precious, but at least on average, medicine is not.

Those interested in healthy life extension should also be interested in the economics of medicine, research and life itself. Attaining an understanding of the basics and the subtleties is well worth it (and a good start would be to add the Ludwig von Mises Institute daily articles and blog to your reading list). Understanding the whys and hows of cost - in the wider sense of the word - is key to understanding how a society of individuals works (or doesn't work) in order to advance medical technology. Thus it is also key to understanding what efforts are likely to help the development of working longevity medicine after the SENS model. Economic thinking is a good thing: embrace it.

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You folks may find this of interest: a long MSNBC interview with biologist James Thompson on topics relating to stem cell research. Some of the more interesting items:

Q: How do you respond to the claim that we have these other sources of stem cells — adult stem cells or cord blood — and there's no need to turn to embryonic cells?

A: We don't. The most studied cell in the whole body, in terms of stem cells, is the hematopoietic stem cell. It can't be grown. So what you do when you do a bone marrow transplant is you take some bone marrow out of you - actually, we do peripheral blood - and we put in another patient without expanding it. There's a clinical need for that expansion step, but it can't be done right now. And hundreds of labs for 30 years have studied that adult stem cell, and that’s the one we know the most about.

...

And again, getting back to the basic science thing: If we study the embryonic stem cells, we learn the basic science. That knowledge is just as likely to be applied to adult stem cells as to the embryonic stem cells. The knowledge goes back and forth. And in the case of the blood, people have failed at growing that cell for three decades. Well, studying that lineage with embryonic stem cells, we might learn the clues to make it growable, and it might be that we still want to use adult stem cells to do that because there are a lot of advantages to that, but the knowledge might come from embryonic stem cells.

Stem cell research really all boils down to a matter of trying to fully understanding and controlling our cells. If researchers can learn to do that, then opportunities to develop cures for aspects of degenerative aging simply fall out of the process.

Q: What are some of those guesses about other technologies?

A: Well, if you take a nucleus and you put it into an oocyte [egg cell], the oocyte knows how to reprogram things. That's a problem that we can study, to understand how that happens. We don't really have a lot of information about how that works, so it's hard to predict how long it's going to take to solve that problem. I'd be surprised if within 10 years we didn't have another way to solve the problem, but it could be that it's a very, very hard problem and it’s going to take a long time to do it.

Q: To find a way for a normal cell to reprogram itself?

A: Right. The message of Dolly is less about cloning, that we can clone Dolly or we can clone people or even do nuclear transfer to make embryonic stem cells; it's that the differentiated state is in principle reversible. And while that was known for a lot of model organisms, and there was even some evidence for that in mammals, Dolly really drove the message home that it was simply a question of time before we understood how to do that.

There's much more; it's well worth reading.

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A change in focus is announced over at Betterhumans, historically a good source of healthy life extension news:

Today, for the first time, users of Betterhumans.com can submit news directly for approval by an editor. It wasn't easy to make this decision, but for several reasons I think that it's for the best. And it reflects a significant change in my thinking about the site.

Betterhumans is doing a good job of straddling the line between old style and new style online media; they're effectively the online face of moderate transhumanism, a news and opinions venture with quite a respectable readership. But the reality of online publishing, as Simon points out, is that it's a place for those who love to do it - not for those who want to make money.

The healthy life extension community has a strong voice; many good writers are blogging and speaking out because they want to, not because they're chasing dollars. If Betterhumans can provide a silver-edge frame (and tens of thousands of page views) for the many folks who can write a silver-edged article (worthy of tens of thousands of page views), then more power to all involved.

So if you blog or write on the topic of healthy life extension, consider making a submission to Betterhumans every now and again. After all, the very worst that could happen is that ten thousand people will have a chance to listen to your point of view and critique your ideas.

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I'll start by saying that I've talked on this topic before, so you should probably head back into the archives to get the background. (I should probably note that I'm far less down on S. Jay Olshansky than I was in October of last year, but my thoughts on A4M are much the same now as then). You can see a summary of the latest press at The Raw Story:

The defamation case is an almost unheard-of attempt to punish academics for comments made in their professional capacity, said experts on libel law and academic freedom. Although UIC is not a defendant in the suit, officials there said they are so concerned about protecting scholarly speech that the school is picking up Olshansky's legal bills.

...

The plaintiffs, osteopathic physicians Ronald Klatz and Robert Goldman, say the 1st Amendment's free speech protections do not cover the actions of Olshansky and co-defendant Dr. Thomas Perls of Boston University. Klatz and Goldman blame the defendants' criticism for a series of recent professional setbacks, including cancellation of an anti-aging conference to have been held this month in Singapore, and termination of a contract to develop anti-aging products that could have been worth $20 million.

I will say that I think it's quite right to be calling out A4M if we feel - as many do - that they are doing just what they accuse obvious frauds in the "anti-aging" marketplace of doing: putting money before ethics and scientific backing, or promoting dubious claims. A4M is a business, and a business with the potential to do a great deal of good for the healthy life extension cause. If they are not living up to that potential, then we as consumers need to stand up and make sure we are being heard - getting businesses to act responsibly is a great deal easier than getting politicians to do the same, after all:

Even those for-profits that cater largely to other businesses - such as A4M - are a great deal more responsive to public opinion (as expressed in dollars and page views) than anything else you might find out there. You can pass on your opinion loud and clear by being an educated, aware, vocal customer. Vote with your wallet; don't buy products branded as "anti-aging." Write outraged letters to businesses that are clearly jumping on the "anti-aging" bandwagon and insulting your intelligence. Support medical research and organizations that take a responsible attitude towards longevity and aging research. Talk loudly about your choices as a consumer and why you are making them - ultimately, those business ventures that succeed determine the look of an entire market. We - people like you and I - decide which business ventures succeed via our choice of where to spend our time and money.

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Aubrey de Grey pointed me to an Australian ABC Radio National show on religion and radical life extension. Here is the summary:

Living longer fascinates us today as much as it ever did. The modern elixirs of life are the special foods and fad diets while the cosmetics industry profits more than ever from our desire to look young. Scientists too, are in on the act as they always have been, though now they have a new weapon - genetic engineering - which promises to be able to cure and prevent the processes in our cells that lead to ageing and death - and to increase our life-spans dramatically. Like magic and alchemy before it, modern science may be on the verge of solving the long quest for immortality. But what if it's our mortality that makes us human? Encounter this week explores the frontiers of ageing.

The RealPlayer audio file can be downloaded here. I'm sure we all know where I stand on the "mortality that makes us human" point - so far as I'm concerned all that mortality makes us is dead. It's hard to be human, or much of anything for that matter, when you're dead. I have nothing against people who want to age and die, but please respect our right to engineer longer, healthier lives for those who want them!

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Mike Linksvayer reports on the recent presentations given by Aubrey de Grey at Stanford University:

The second talk, apparently more intended for biologists, was a repeat of the first to a disappointing extent. I was prepared to understand very little, but de Grey only spoke for awhile on one of his proposed solutions to one of the seven types of damage - extracellular junk. The solution takes a cue from bioremediation: find microbes that break down the extracellular junk. Where? Human remains of course. From Appropriating microbial catabolism: a proposal to treat and prevent neurodegeneration:

"Soil microbes display astonishing catabolic diversity, something exploited for decades in the bioremediation industry. Environments enriched in human remains impose selective pressure on the microbial population to evolve the ability to degrade any recalcitrant, energy-rich human material. Thus, microbes may exist that can degrade these lysosomal toxins. If so, it should be possible to isolate the genes responsible and modify them for therapeutic activity in the mammalian lysosome."

Neat idea. Later de Grey said that this idea is the easiest to explain to non-specialists and that the others that he has personally worked on would have required far longer to introduce than the hour lecture format allowed.

de Grey is attempting to jump start anti-aging interventions with the Methuselah Mouse Prize[s] for extending the lifespan of mice, inspired by the X Prize. His "engineering" approach sounds good to me and I wholly endorse the goal of defeating aging. I will donate more once more information is provided about the participating scientists and their mice - not much is available at this point.

I'll take that as a sign that we volunteers need to put more effort into obtaining information from the Mprize competitors and potential competitors - as anyone who works in science knows, getting usefully formatted information out of busy scientists is hard work in and of itself. However, donors who are invested in the march towards healthy life extension technologies (which would be all of them, I hope) need to see progress in order to validate their donations - I know I feel that way about the use of my money. So, more effort needed!

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After my recent posts on the future of open source biotechnology, I received an email from Ray Van De Walker to provide a contrary viewpoint:

Briefly, my credentials:

I have seven years of experience developing biomedical software. Several products have achieved FDA and CE approvals, and are in mass-produced use by patients.

Here's the problems:

1. The market itself does not tolerate design defects. The established standard is less than one unanticipated risk per billion patient hours, and the evidence trail has to hold up in court or sellers will be successfully sued by patients for whom the therapy failed.

2. In the U.S., to advertise or sell a therapy, the FDA requires evidence of safety and effectiveness. The European union just requires evidence of safety; effectiveness is left to doctors and patients.

a) Therefore the therapy has to have traceable continuity in testing or safety engineering, including maintenance of test results at an agency or person that can be held liable by the FDA or (in the case of the EU) a government's regulatory agency. Most organizations and sane people will not accept liability without an income stream to pay for the liability insurance, which of course is extremely expensive for medical therapies.

b) To meet effectiveness requirements in the U.S. there must be patient trials to prove the therapy. The patient trials are extremely expensive, because the doctors, hospital time, etc. are expensive (Most do not work pro-bono). I.e. close to quarter billion dollars for a major drug using a new metabolic pathway to be certified. Medical devices (much cheaper) only cost 25 to a 100 million if the therapy they perform is not experimental.

Contrast that with open-source software, which basically says that if there's a defect, then it's up to the user to fix it or live with it.

Production would not be a problem, I think. The market selling open source therapies could be much like that for generic drugs. The producers would have to have certified quality organizations, but generic producers already do that.

For my part, I have to say that agree with these two central points:

• Centralized regulation kills open source approaches to development for exactly the same reasons it damages the market - imagine the consequences of centralized regulation of server software. We'd still be paying $50,000 for 200MHz machines and hand-testing factory RAM for errors.

• Many medical applications require a level of reliability that traditional-model open source groups do not approach. The same is true of many software applications.
  

I do think that we can fairly quickly point to a large swathe of medicine and medical science that could benefit from improvements in lower-reliability methodologies. The practice of neurosurgery will probably not be a part of this swathe - but I'm willing to bet that most in vitro and simulational medical research certainly will be.

A larger range of medicine would also benefit from lower-reliability methods in the absence of centralized, monolithic, risk-averse regulation - say, with distributed, competitive, accountable review instead, allowing individuals to adopt risk levels as they feel appropriate, just as in all other walks of life. Most applications of medicine and most basic medical research does not need the fault tolerance expected of air traffic control or rocketry systems ... or neurosurgery for that matter.

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Researcher Rafal Smigrodski was kind enough to post a preview of a forthcoming Rejuvenation Research paper to the ExI Chat List today:

A few months ago I promised to post an article on mitochondria and aging which I was writing with Shaharyar Khan, and finally I can keep my promise. "Mitochondrial microheteroplasmy and a theory of aging and age-related disease" will be published in Rejuvenation Research in August. Here is the text (without figures) and I can send the pdf to anyone interested.

...

We implicate a recently described form of mitochondrial mutation, mitochondrial microheteroplasmy, as a candidate for the principal component of aging. Microheteroplasmy is the presence of hundreds of independent mutations in one organism, with each mutation usually found in 1 - 2% of all mitochondrial genomes. Despite the low abundance of single mutations, the vast majority of mitochondrial genomes in all adults are mutated. This mutational burden includes inherited mutations, de novo germline mutations, as well as somatic mutations acquired either during early embryonic development or later in adult life. We postulate that microheteroplasmy is sufficient to explain the pathomechanism of several age-associated diseases, especially in conditions with known mitochondrial involvement, such as diabetes (DM), cardiovascular disease, Parkinson's disease (PD), and Alzheimer's disease (AD) and cancer. The genetic properties of microheteroplasmy reconcile the results of disease models (cybrids, hypermutable PolG variants and mitochondrial toxins), with the relatively low levels of maternal inheritance in the aforementioned diseases, and provide an explanation of their delayed, progressive course.

As long-time readers will be aware, Rafal has an enviable position with a research group focusing on mitochondria, working on important projects such as tools to manipulate and repair mitochondrial damage. While there is still a great deal of uncertainty in the relationship between mitochondria and aging (all the more reason for more funding), it is quite clear that this is a very promising avenue of research for healthy life extension. As I'm sure you know, repair of mitochondrial mutations is one of the seven pillars of Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS).

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Thoughts on the culture of entitlement are noted by Glenn Reynolds:

Americans now feel entitled to spend nearly a third of their adult lives in retirement. Their jobs are less physically demanding than their parents' were, but they're retiring younger and typically start collecting Social Security by age 62. Most could keep working - fewer than 10 percent of people 65 to 75 are in poor health - but, like Bartleby the Scrivener, they prefer not to.

I've discussed this issue in the past and noted that the real problem is not that people feel entitled, but that our vast, crooked, centralized government can be manipulated to enable those who feel entitled to steal resources from the rest of us.

A culture of entitlement is damaging for everyone, at every age: we are all, ultimately, responsible for our own lives, health, wealth and happiness. If ever-larger capable, healthy, active portions of the populace continue to engineer our society to obtain resources for themselves at the expense of others, the system will collapse.

This all ties back into the giant Ponzi scheme that is social security - essentially a way for people who are, on average, wealthier to vote themselves resources from people who are not. The problem is not that people are going to be people, but that centralized, massive government enables the worse aspects of human nature to cause so much economic harm.

A related area of entitlement - accompanied by political debate, puffery and grave misunderstandings over the way the world actually works - is medical provision and insurance. Ronald Bailey takes a look and nails the real costs:

Which suggests the following thought experiment—what if the United States had nationalized its health care system in 1960? That would be the moral equivalent of freezing (or at least drastically slowing) medical innovation at 1960 levels. The private sector and governments would not now be spending so much more money on health care. There might well have been no organ transplants, no MRIs, no laparoscopic surgery, no cholesterol lowering drugs, hepatitis C vaccine, no in vitro fertilization, no HIV treatments and so forth. Even Canadians and Britons would not be satisfied with receiving the same quality of medical care that they got 45 years ago.

Everybody pays more to obtain improved pharmaceuticals, imaging technologies, cancer therapies, and surgical techniques. The happy result is that average life expectancy has increased by about eight years since 1960.

The encroachment of socialism in medicine in the US should be of grave concern to those interested in longer, healthier lives and a future of better medical technology. Without a dynamic free market, the pace of medical progress grinds to a halt - regulation could literally cost us our lives. As Bill Walker noted:

If telomerase inhibitors were a new kind of computer chip, they would have been on every Wal-Mart pharmacy shelf and selling for ten dollars a bottle by now.

And there would be twenty competing review organizations providing responsible, comprehensive risk-evaluations for another few dollars. This sentiment is true of every aspect of medical research, every new potential therapy that could help with age-related disease or aging itself. The present system of centralized review gives us the worse of all worlds - it greatly slows research while still being largely ineffective at its stated goals.

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The growing Longevity Meme Folding@Home team has been doing well over the past few weeks, powering past the 700 mark in the team listings. A warm welcome to the new folders and congratulations to all taking part - keep up the good work.

I'll set a goal now: when we hit 500, I'll be handing out commemorative team goodies for all the members. If you have opinions on the type of handouts and the logos they should bear, just post your thoughts below. If you're not already signed up for Folding@Home, then now would be the time to get involved! Make use of all that spare processor time currently going to waste on your home machine and help to advance the cause of medical science.

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It's always good to see the basic concepts of healthy life extension permeating throughout the scientific community - and being expressed more forcefully, since scientists tend to be conservative for reasons relating to funding and common human nature. So I am pleased to see this abstract from the Journal of Hypertension:

Objective: Although the quest for longevity is as old as civilization itself, only recently have technical and conceptual advances in genomics research brought us to the point of understanding the precise molecular events that make us age. This heralds an era when manipulations of these will enable us to live longer, healthier lives. The present review describes how recent experimental strategies have identified key genes and intracellular pathways that are responsible for ageing and longevity.

Findings: In diverse species transcription factors belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have been found to be crucial in downstream suppression of the life-shortening effects of insulin/insulin-like growth factor-I receptor signalling pathways that, when upregulated, accelerate ageing by suppression of FOXO. The various adverse processes activated upon FOXO suppression include increased generation of reactive oxygen species (ROS). ROS are pivotal for the onset of various common conditions, including hypertension, atherosclerosis, type 2 diabetes, cancer and Alzheimer's disease, each of which shortens lifespan. In humans, FOXO3a, as well as FOXO1 and -4, and their downstream effectors, could hold the key to counteracting ageing and common diseases. An understanding of the processes controlled by these FOXOs should permit development of novel classes of agents that will more directly counteract or prevent the damage associated with diverse life-threatening conditions, and so foster a life of good health to a ripe old age. Just like caloric restriction, lifespan can be increased in various species by plant-derived polyphenols, such as resveratrol, via activation of sirtuins in cells. Sirtuins, such as SIRT1 in mammals, utilize FOXO and other pathways to achieve their beneficial effects on health and lifespan.

Conclusion: Lifespan is tractable and basic mechanisms are now known. Longevity research complements and overlaps research in most major medical disciplines. Current progress bodes well for an ever-increasing length of healthy life for those who adapt emerging knowledge personally (so-called 'longevitarians').

I think the author coined "longevitarians," since that's the first time I've heard it, but we'll let that pass. The rest is quite to the point - and the more scientists who stand up to say it, the better. We know more than enough to make a serious start on the fight to cure aging! If you would like to learn more about the science here, you can find a very educational discussion on FOXO and related areas of genetics in a Fight Aging! post from early 2004.

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If you want to get in under the early registration deadline for the Second Strategies for Engineered Negligible Senescence (SENS) Conference in September then you are cutting it fine - your chance to save money on the registration fee is gone after June 15th.

The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Methuselah Mouse Prize), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - reverse - those changes, rather than merely to slow down their further accumulation.

The SENS 2 program as it stands right now promises a good conference - you'll see many familiar names and promising fields of science if you're someone who keeps tabs on biogerontology and other aging research. The Ellison Medical Foundation session on the removal of intracellular waste products - a growing area of interest in the medical research community - looks to be particularly fascinating.

Also of note:

This year's SENS Lecture, provisionally entitled "Stem cells, SCNT and the rejuvenation imperative", will be given by Dr. Michael West, CEO of Advanced Cell Technology.

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Calorie restriction blogs are starting to spread - I think that this is a very good thing. The practice of calorie restriction with optimal nutrition (CRON) is as simple as a rock on a table once you have some experience; with the requirements of a calorie count and an optimal nutrient intake in hand everything else tends to fall into place and become obvious. Getting to the point of being experienced has always been the question mark in the process, however. What foods, what methods, what are the common stumbling points ... what exactly do I do today? A good calorie restriction blog is a real help for those working their way into the practice of this lifestyle option for healthy life extension. Here are some for your reading pleasure:

• April's CR Diary
• CRON101
• CRON Diary
• CRONing for a future...
• Jay Fox's CR Blog
• See Spot CRON

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In the last Longevity Meme Newsletter I offered the following opinions on Protandim, current research into tuning the human metabolism and other longevity-related tinkering:

It is somewhat frustrating to watch well-oiled publicity machines going to work to promote what is essentially useless junk in the grand scheme of things. There is some moderately interesting science in the intersection of metabolism and longevity at the bottom of all this, but it's not science that will deliver firm answers or meaningful progress any more rapidly than the folks currently working - from a far more sound scientific basis - on calorie restriction mimetics. It certainly won't deliver any surety in whatever bottled compound they're selling today.

As I've remarked before, the whole field of metabolic science is useful, but any healthy life extension to come from it will be a form of tuning the machine - using better motor oil, running the engine at the most efficient speed, that sort of thing. This suffers from much the same problems as supplementation - you can spend as much time and money as you like tinkering and experimenting ... are you ever really sure you are making progress? Is it a productive use of your resources once you have gone past the basics?

Ian Clements wrote to me with the following comments:

This has, for me, highlighted the two differing models (which are not necessarily mutually exclusive) which may be a source of confusion: on the one hand, we may already be immortal, but are held back from achieving this by a myriad of successive minor failures of our body system; on the other, we have already more or less reached our natural life-span limit with our traditional living methods, and therefore need a radical alteration (growing replacement organs like lizards; reversing the present gradual decline of complete replacement of failing sub-systems).

It is not clear (to me anyway) which of these models more correctly describes us (or any living organism for that matter).

If the former, let's call it Model A, is true, then addressing each and every issue as it comes up or for which new solutions are found may well enable us individually live longer and the average life span to increase. This approach appears to be the one which has worked for the last 100+ years, and explains the data of a linear increase of the numbers and percentages living beyond 100 years. Model A is probably the one most of us use at present in practice, as we incorporate each successive proven (or plausable) new method and life-style alteration (regular exercise, not smoking, anti-oxidants, etc).

Model A was/is based on the belief that we can extend our healthy life up to an implicit maximum, but not extend beyond that - this last phrase is the one I now wish to challenge (implicit in its turn, byt the linear extension of lower mortality rates beyond about 80). However, we can revise our view of Model A (to the status of Immortality model): that is, immortality can be achieved by incorporating (cautiously) each and every proven improvement as they come along and therefore (perhaps) stay ahead of the ageing processes otherwise taking place.

The additional (Model B) idea recently introduced is the lure of immortality by some radical new methods - such as growing new organs from our existing cells (as distinct from transplants) to replace failing/ageing ones. I also put CR mimetics in this class, as this would probably require a lifelong intake of some drug to cause our cells to do the mimicing.

One of the benefits of age is that you get experience of many things, as distinct from just reading about them. And one of the things I've become increasingly convinced about is that gradual change/evolution is more successful than radical or revolutionary change. As a scientist, I have an open mind and will let the evidence decide; but until that happens (either way), I'll use the step-by-step approach to life extension (as, I'm sure, most others will). What I am highlighting here is that there needs to be a more explicit recognition of the two alternative models, and to be aware that Model B is not the only game in town - that Model A should not be either dismissed or consigned to the band-aid category; it just might be the only one that works.

Thus, far from tinkering being only a process of minor improvement whilst awaiting the Holy Grail of a radical complete solution, it (Model A) may be the only solution. If so, then far from needing to get started on anti-ageing research, we are already within the midst of it - after all, doubling the average age of death (well, 25%-50% if we ignore the distortion of including the under 5s mortality figures) in a hundred years is not to be sniffed at; couple that with the healthier old and linear improvements in mortality figures above 75 or so for several decades indicates that Model A has 'legs'.

Immortality in these comments refers to physical immortality, a state of "vulnerable agelessness."

I think I could assign all valid scientific efforts to extend healthy life span to the category of gradual change - but some gradual change is faster than others. No-one is claiming that Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS) could happen overnight; advances would be gradual ... but I see such work as more effective on a per dollar investment basis than working with supplements and metabolism. As is pointed out above, it's not a zero-sum, mutually exclusive sort of choice, however - in fact, everything that is not SENS is pretty well entrenched in the private and public research communities already. It's just that the resulting - largely incidental - gains in life span are not enough, and show no signs of accelerating rapidly. We need to add further, better strings to our bow if we want to avoid the consequences of untreated degenerative aging.

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Papers on calorie restriction and its underlying mechanisms for healthy life extension are in press for the latest Mechanisms of Aging and Development journal - a special issue focused on this topic. Of note is Calorie restriction and SIR2 genes - Towards a mechanism by Leonard Guarente (cite doi:10.1016/j.mad.2005.03.013):

Calorie restriction is the first and most compelling example of life extension in mammals. Much speculation about how CR works has focused on ideas of what causes aging. Since these causes themselves are much disputed, I have instead focused my thinking on lessons from simple model organisms, which have emerged from recent genetic studies. These findings can now be integrated with numerous, elegant studies on CR over the decades, which provide a treasure trove of information about physiological changes that are elicited by this regimen. In this paper, I present data showing that the SIR2 gene is a strong candidate to regulate CR in the simple model organisms, such as yeast and Drosophila. I then summarize what is known about the mammalian Sirt1 as it relates to physiological changes during CR, and discuss how this mechanism may impact on life span, as well as diseases of aging.

There are a large number of other abstracts well worth perusing for those interested in closely following progress on aging and longevity research.

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I thought I would direct your attention to a nice article on current scientific interest in microRNAs:

One of the medical marvels of stem cells is that they continue to divide and renew themselves when other cells would quit. But what is it that gives stem cells this kind of immortality? Researchers report in the journal Nature that microRNAs - tiny snippets of genetic material that have now been linked to growth regulation in normal cells as well as cancer growth in abnormal cells - appear to shut off the "stop signals" or brakes that would normally tell cells to stop dividing.

As soon as you're down in the depths of cellular mechanisms, you run into links to both cancer and aging:

In a commentary, Dr. Paul Meltzer of the National Human Genome Research Institute said microRNAs "are now definitely linked to the development of cancer."

...

And now that the researchers have found that too few microRNAs are bad for stem cells, they want to see what an abundance of microRNAs will do. Perhaps the right recipe can give even ordinary cells a touch of "stem-cellness."

"We are right now testing that, by overproducing microRNAs in the daughter cells that have begun to differentiate," Ruohola-Baker said. "Maybe this would also help aging stem cells. Maybe you can keep them dividing by using more microRNAs."

Other recent work demonstrates that helping aging stem cells would certainly be a good thing insofar as health and longevity are concerned. Human cells are basically finite state machines on a number of different levels. The only difference between an embryonic stem cell and an adult, differentiated cell lies in the state of the inner machinery (give or take a few gross oversimplifications). The more we understand, the more we can do - we are presently in the very earliest days of a medical revolution, but at the far end of the path of complete cellular control we will have cures for all diseases ... and for degenerative aging itself.

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The World Health Network is the online face of the American Academy for Anti-Aging Medicine (A4M), yet another of the predominantly old school organizations in the wider healthy life extension community that leave me with mixed opinions. I have been watching A4M beat their online presence - a website with a respectable Alexa traffic rank of 52,000 or so - into shape over the past few years. Over that time, the face of A4M as represented by their website - and interviews with the founders in the mainstream media - has evolved to present a much more forward-looking, responsible perspective. Less hormone therapy and supplements, more stem cells, genetics, and modern medical research. I think this is probably best encapsulated by a glance at their front page news headlines and their comparatively new (re)definition of anti-aging medicine:

Anti-aging medicine, an extension of preventive health care, is the next great model of health care for the new millennium. This model is based on the early detection, prevention, and reversal of aging- related diseases. All diseases fall into four categories; the first three-inherited genetic disease, infectious disease, and trauma-account for only 10% of the cost for treating all disease in America. Ninety percent of all health care dollars are spent on extraordinary care in the last two to three years of life. A grand total of fifty percent of the US health care budget is spent on the degenerative diseases of aging [Health Care & Finance Administration, 1996.] One hundred million Americans are currently being treated for one or another degenerative disease at a health care cost of more than $700 billion per year. If we really want to make an impact on health care in this country and in the world, we must focus on the degenerative diseases of aging. If we can slow aging, we can eliminate more than 50% of all disease overnight. We can alter this dreadful course by preventing, delaying, or reversing the diseases associated with aging.

As I've said before, A4M says a lot of the right stuff and their hearts do appear to be in the right place - it's their implementation that leaves much to be desired. While I would like to be able to claim some credit for pushing their public outreach in this direction (you'll notice Longevity Meme RSS feed content showing up on the World Health Network occasionally, and this new definition surfaced around the time I published "What is Anti-Aging?"), I'm sure they've arrived here largely of their own accord and by watching the success of others far more vocal and influential than myself.

It remains to be seen just how deep this exterior gloss will penetrate into the organization; the A4M core business relies of conferences and association with the less reputable side of the marketplace. This continues to be a bone of contention and - I believe - ensures that A4M brings as much harm as help to the future of healthy life extension.

As a final thought, it is the desires of the public that ultimately shape for-profit organizations. Even those for-profits that cater largely to other businesses - such as A4M - are a great deal more responsive to public opinion (as expressed in dollars and page views) than anything else you might find out there. You can pass on your opinion loud and clear by being an educated, aware, vocal customer. Vote with your wallet; don't buy products branded as "anti-aging." Write outraged letters to businesses that are clearly jumping on the "anti-aging" bandwagon and insulting your intelligence. Support medical research and organizations that take a responsible attitude towards longevity and aging research. Talk loudly about your choices as a consumer and why you are making them - ultimately, those business ventures that succeed determine the look of an entire market. We - people like you and I - decide which business ventures succeed via our choice of where to spend our time and money.

In short, you have a great deal of power in these matters - make use of it.

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Nick Gillespie notes at Hit & Run:

leading opponents to embryonic stem cells are not simply worried about the embryo issue - they fundamentally question whether we should be intervening to prolong and improve human lifespans and ameliorate human suffering.

...

George W. Bush's bioethics kingpin, Leon Kass, is on record as saying, "The finitude of human life is a blessing for every individual, whether he knows it or not." Like Fukuyama and others that Reason's Ron Bailey has pegged as "pro-death," the core issue is not how we might extend life but whether we should.

As I've pointed out in the past, it is hard to even hold a debate with people who push the horrific concept of using government power to block research and treatments for age-related degeneration. It amounts to promoting murder by legislation.

Glenn Reynolds echoes Nick Gillespie's view, made in response to the latest in embryonic stem cell research:

This would defuse the pro-life opposition. It wouldn't address the concerns of those - like, say, Leon Kass - who are uncomfortable with dramatic advances in medical technology for other reasons.

Both give too much respect for these views; there comes a time when you have to stand up and tell the other side that they are far outside the bounds of discourse. You can't hum and nod thoughtfully in response to a proposal that involves forcing billions to suffer and die.

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Pete from supplement company Relentless Improvement has announced that he will be blogging from the 34th annual meeting of the American Aging Association and 19th annual meeting of the College of Clinical Gerontology at the Marriott City Center in Oakland, CA. The first two entries are up already. His commentary comes from a supplement industry point of view, needless to say, but since none of the rest of us are there to blog about the conference, good for him for taking the time to do so.

One thing I learned - there is no shortage of disagreement on any given view. Keep in mind the folks here were all at least PhD's, and most of them working on the very bleeding edge of research. Another surprise, just how little is known about the aging process. I am sure the majority of physicians are fine, hard working people, but they simply cannot keep up with all the latest breakthroughs. The goods news is that a wide variety of things are being looked at in the anti-aging field.

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Well, I'm happy to report a shiny silver lining to this sudden barrage of Protandim-related marketing and nonsense - it has provoked the always worthwhile Jay Fox into writing another of his excellent blog-essays on the effectiveness of "anti-aging" therapies:

This discussion actually comes at a fortuitous time, because of an article recently written by renowned biogerontologist Aubrey de Grey. In his article, de Grey questions the idea of trying to measure the "rate of aging", since nearly all currently or hoped-to-be used methods of measuring the rate of aging are inherently flawed, and will essentially be useless in the long term.

I know you came here to read about Protandim, but let's digress a bit on a tangent related to measuring the effectiveness of so-called "anti-aging" pills: Gompertz Law. I promise it'll make sense, eventually...

It's well worth your time to read; hopefully it should help put the light and noise surrounding comparatively trivial items like Protandim into a better context. He makes many of the points that I was aiming for in my commentary on Protandim - namely that it's a drop in the bucket, and that chasing the drops is a bad idea when the same level of effort will eventually produce streams or rivers of progress in medical science, longevity and real anti-aging therapies.

So what should we make of Protandim? Well, to date, the only intervention (short of genetic manipulation) shown to significantly decrease the slope of the Gompertz Curve (and thus, likely add a lot of extra years to the lifespan of young people) is calorie restriction. Of all the other chemicals found to increase lifespan, most do so simply by shifting the Gompertz Curve down.

...

If all that Protandim can accomplish - and until long-term studies are carried out, the best we should hope for - is to shift the Gompertz Curve down, then an older person will see about as much benefit as a younger person: a modest, perhaps even small, absolute increase in remaining years before death.

...
So if you have money to spend, and you're considering spending it on Protandim, please consider helping out a cause that will one day make aging itself a thing of the past. Please donate to the M Prize!

I couldn't have said it better myself.

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It seems that Lifeline Therapeutics, marketeer for Protandim, has netted venture capital:

Lifeline Therapeutics, Inc. (OTCBB: LFLT), a health company dedicated to developing products that help people live better, healthier and longer lives by fighting oxidative damage in the body, today announced the company completed an $8 million private placement. Keating Securities, LLC acted as sole placement agent of the financing. Proceeds from this funding will be used to eliminate the Company's debt of $3 million, for U.S. research surrounding its Protandim product and as working capital related to the development of new antioxidant therapies.

Through the miracle of product placement - available to those bearers of the magic green tokens we call "money" - this coincides with a nice healthy examination of Protandim and supporting science at ABC. Such is the way the world works, nothing out of the ordinary there.

What makes me a little more skeptical than normal when it comes to pills and anti-aging claims is the history of this particular company. The short version can be told as follows:

• CereMedix tests a compound that could extend life span by mitigating oxidative stress. This is CMX-1152, described on the CereMedix website (scroll down a bit on that page).
• Lifeline is founded on the basis of a licensing deal with CereMedix; the Protandim name is later assigned to CMX-1152
• Around this time, I begin to comment on this deal, CMX-1152, Protandim and Lifeline. Some of my comments are promptly misquoted, rewritten and used as a glowing endorsement on the Lifeline website; not an auspicious start. My grumbling on that topic can be seen in the Immortality Institute thread on Lifeline.
• For reasons that remain unclear, Lifeline does not proceed with CMX-1152, but rather begins looking for a new product to market under the existing brand name of Protandim.
• For a time, Lifeline continues to use the experimental results from CMX-1152 to tout their new non-CMX-1152 product, which could charitably be described as a potpourri of existing antioxidant supplements. This also is documented in the the Immortality Institute thread on Lifeline. Not cricket, gentlemen.
• Now we see a more mature offering from Lifeline, at least in the marketing department. They have retained the focus on oxidative stress, but are building a brand on the work of different scientists.
• So far as it goes, it looks like Lifeline is still selling the potpourri of existing supplements.

So, this is just like the circus over resveratrol by the looks of things; some moderately interesting science in the intersection of metabolism and longevity buried by a cartload of marketing. We may, or may not, find out something interesting about the long term effects of the product on humans in a decade or so. As for resveratrol, I have no doubt some folks will make money from Protandim, but this is a distracting sideshow for anyone interested in meaningful healthy life extension. The immediate future of health and longevity is not in pills, folks. There isn't anything out there proven to do better than simple calorie restriction - and even that isn't so great in the grand scheme of what is possible. If you want to live a much longer, much healthier life, don't spend all your time chasing after better pills and tinkering with your metabolism. Instead put your energies into supporting the sort of research that will put an end to age-related degeneration once and for all - that could happen within our lifetime, but only if we stand up and make sure of it.

UPDATE: Some interesting comments from Pete Estrep:

Well, they certainly have guts to present the data on this web page, http://www.protandim.com/scientific-studies.htm

Around thirty mice and thirteen subjects in the human trial. They draw a line through points that have an R^2 of 0.02. This means that the points are almost randomly scattered. Sure, you can draw a line through these points but it is almost meaningless. I won't be buying Protandim until they generate a lot more data.

FYI, the stuff is made of herbs (ashwagandha, and extracts of milk thistle, bacopa, green tea, and turmeric). They claim it works by increasing levels of protein antioxidants. If this is true I am interested in the mechanism since you can increase levels of endogenous antioxidants by increasing oxidative stress and damage. This is similar to certain claims of compounds increasing levels of DNA repair enzymes. The most reliable way to do this is to increase DNA damage because you will get elevated levels of repair enzymes in response to damage. The effect Protandim has on lipid peroxidation is irrelevant since lipids are replaceable, it is just a proxy for damage to more precious stuff, like DNA.. What we really want to know is what Protandim does to the rate of DNA damage. Does it cause less damage, more, no change? Unknown.

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The ever-useful Randall Parker has more on recent research into protein restriction versus calorie restriction in fly experiments. Be sure to look at Robert Bradbury's comment to the post as well:

There has always been some evidence that certain types of protein restriction may extend lifespan via mechanisms other than strict caloric restriction. One has to look at what caloric restriction probably does -- it probably decreases the production of free radicals from the mitochondria and therefore the downstream oxidative damage. However what protein restriction does is signal the upregulation of the recycling of proteins, esp. damaged proteins. So you can lower the ratio of damaged proteins to good proteins by either reducing the source of the damage or increasing the rate at which the damage is removed. Now, if some of the damaged proteins happen to be those in the mitochondria (which is likely to be the case) then protein restriction may increase the fraction of mitochondria with undamaged proteins which are less likely to cause free radical damage (damaged [sloppy] mitochondrial proteins increase free radical production).

Will this translate to humans? Who knows, and too early to say. Plain, vanilla calorie restriction still has robust science behind it for human health and longevity - but it's a far cry from any form of plausible and effective longevity therapy or radical life extension.

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I really don't have anything bad to say about people who are set on aging and dying - I just think that most of them haven't really thought it through, at least not to the point of understanding just how much personal suffering is going to be involved. (Which is why the old age simulation suit is such a great idea). We humans are just not all that well endowed when it comes to empathy and planning ahead. If we were, you can be sure that age-related degeneration and death would be solved problems already.

Regardless, there are still those folks who have thought it through and decided that aging and dying is for them. I'm certainly not one to argue against the value of freedom and personal choice, even if I'm quite sure that most of these people will make glad use of cures for age-related degeneration and death further down the line, despite having done nothing to help bring about this bright future of medicine.

No, the people I have a real problem with are those who seem set on forcing others to suffer and die. Personal acceptance of values that denigrate science and medicine and glorify suffering and death is one thing, but setting out to force the consequences of these views on others is nothing less than horrific.

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