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Progress for The Longevity Meme Folding@home Team – Update of August 4, 2014 – by G. Stolyarov II

Progress for The Longevity Meme Folding@home Team – Update of August 4, 2014 – by G. Stolyarov II

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The New Renaissance Hat
G. Stolyarov II
August 4, 2014
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I am pleased to announce significant progress for The Longevity Meme Folding@home team – a group of volunteers who donate their computing power to perform protein-folding simulations that could one day result in cures for major diseases and the lengthening of human lifespans.

Statistics for the full month of July 2014 show significant improvement compared to both May and June – a total of 3,957,851 points earned by team members, up from 2,368,216 in June (a 67.1% increase) and from 1,624,448 in May (a 143.6% increase). The number of workunits processed has risen even more astronomically, from 1,396 in May to 1,963 in June, to 7,814 in July – a near-quadrupling in one month. Here is a summary of monthly production for The Longevity Meme team from the Extreme Overclocking statistics page. Longevity_Meme_Folding_Statistics_8-4-2014The increase is attributable to a rise in active member participation. Many previously active members have resumed folding, and new contributors have joined us. My offering of five tiers of Open Badges for contributors who reach certain point thresholds has attracted at least one user thus far – RonnyR (Ronny Risøen), whom I would like to thank for his tremendous contribution thus far – nearly 2.5 million points in just three months! He is The Longevity Meme team’s most rapid producer at present. Other substantial contributions during the recent months were made by users ralmcruz, TMichael, Gennady Stolyarov II (myself), LongandLasting, Volcanic, dreilopz, and sigma957. All of these users have earned Open Badges for their work and should contact me at gennadystolyarovii@gmail.com so that I could send them a code for claiming their badges.

Participation in protein-folding initiatives such as Folding@home is an excellent way to promote the message of indefinite life extension and to personally accelerate the advent of research breakthroughs that could actually lengthen our lives. We have made impressive strides forward, but we still need additional contributors to raise The Longevity Meme team’s ranking on the Folding@home leaderboard and thereby raise the prominence and reach of life-extension ideas. Join us today!

Another View of Aging Science: That We Don’t Know Enough – Article by Reason

Another View of Aging Science: That We Don’t Know Enough – Article by Reason

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The New Renaissance Hat
Reason
June 27, 2014
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Early this month I pointed out an example of the viewpoint on aging research that focuses on drugs, lifestyle, and metabolic manipulation and sees present work in that area to be a matter of significant and ongoing process. I disagree, for reasons that were explained in that post. Today, I’ll take a glance at a different view of the science of aging and longevity, one that is far more popular in the mainstream research community, and with which I also vehemently disagree.

Researchers in this field might be loosely divided into three camps, which are as follows ordered from largest to smallest: (a) those who study aging as a phenomenon without seeking to produce treatments, (b) those who see to slow aging through development of means to alter the operation of metabolism, such as calorie restriction mimetic drugs, and (c) those who aim to produce rejuvenation biotechnology capable of reversing aging. The vast majority of the aging research community at present consider that too little is known of the details of the progression of aging to make significant inroads in the design of treatments, and that the way forward is fundamental research with little hope of meaningful application for the foreseeable future. This attitude is captured here:

Let me ask you this: ‘Why can’t we cure death yet?’

Quote:

We can’t ‘cure death’ because biology is extremely complicated. Without a fundamental understanding of how biological organisms work on a molecular level, we’re left to educated guesses on how to fix things that are breaking in the human body. Trying to cure disease without a full understanding of the underlying principles is like trying to travel to the moon without using Newton’s laws of motion.

The reason we haven’t cured death is because we don’t really understand life.

This is only half true, however. It is true if your goal is to slow down aging by engineering metabolism into a new state of safe operation in which the damage of aging accumulates more slowly. This is an enormous project. It is harder than anything that has been accomplished by humanity to date, measured on any reasonable scale of complexity. The community has only a few footholds in the vast sea of interactions that make up the progression of metabolism and damage through the course of aging, and this is despite the fact that there exists an easily obtained, very well studied altered state of metabolism that does in fact slow aging and extend life. Calorie restriction can be investigated in almost all laboratory species, and has been the subject of intense scrutiny for more than a decade now. Yet that barely constitutes a start on the long road of figuring out how to replicate the effects of calorie restriction on metabolism, let alone how to set off into the unknown to build an even better metabolic state of operation.

Listing these concerns is not even to start in on the fact that even if clinicians could perfectly replicate the benefits of calorie restriction, these effects are still modest in the grand scheme of things. It probably won’t add more than ten years to your life, and it won’t rejuvenate the old, nor restore any of their lost functionality. It is a way of slowing down remaining harm, not repairing the harm that has happened. All in all it seems like a poor use of resources.

People who argue that we don’t understand enough of aging to treat it are conveniently omitting the fact that the research community does in fact have a proven, time-tested consensus list of the causes of aging. These are the fundamental differences between old tissue and young tissue, the list of changes that are not in and of themselves caused by any other process of aging. This is the damage that is the root of aging. There are certainly fierce arguments over which of these are more important and how in detail they actually interact with one another and metabolism to cause frailty, disease, and death. I’ve already said as much: researchers are still in the early days of producing the complete map of how aging progresses at the detail level. The actual list of damage and change is not much debated, however: that is settled science.

Thus if all you want to do is produce good treatments that reverse the effects of aging, you don’t need to know every detail of the progression of aging. You just need to remove the root causes. It doesn’t matter which of them are more or less important, just remove them all, and you’ll find out which were more or less important in the course of doing so – and probably faster than those who are taking the slow and stead scholarly route of investigation. If results are what we want to see then instead of studying ever more esoteric little corners of our biology, researchers might change focus on ways to repair the known forms of damage that cause aging. In this way treatments can be produced that actually rejuvenate patients, and unlike methods of slowing aging will benefit the old by reversing and preventing age-related disease.

This is exactly analogous to the long history of building good bridges prior to the modern age of computer simulation and materials science. With the advent of these tools engineers can now build superb bridges, of a quality and size that would once have been impossible. But the engineers of ancient Rome built good bridges: bridges that allowed people to cross rivers and chasms and some of which still stand today. Victorian engineers built better bridges to facilitate commerce that have stood the test of time, and they worked with little more than did the Romans in comparison to today’s technologies. So the aging research community could begin to build their bridges now, we don’t have to wait for better science. Given that we are talking about aging, and the cost of aging is measured in tens of millions of lives lost and hundreds of millions more left suffering each and every year, it is amazing to me that there are not more initiatives focused on taking what is already known and settled about the causes of aging and using that knowledge to build rejuvenation treatments.

What we see instead is a field largely focused on doing nothing but gathering data, and where there are researchers interesting in producing treatments, they are almost all focused on metabolic engineering to slow aging. The long, hard road to nowhere helpful. Yet repairing the known damage of aging is so very obviously the better course for research and development when compared to the prospect of an endless exploration and cataloging of metabolism. If we want the chance of significant progress towards means of treating aging in our lifetime, only SENS and other repair-based approaches have a shot at delivering. Attempts to slow aging are only a distraction: they will provide a growing flow of new knowledge of our biochemistry and the details of aging, but that knowledge isn’t needed in order to work towards effective treatments for aging today.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

“Protein Folding for Life Extension” Open Badges for Folding@home Participation – Post by G. Stolyarov II

“Protein Folding for Life Extension” Open Badges for Folding@home Participation – Post by G. Stolyarov II

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The New Renaissance Hat
G. Stolyarov II
June 8, 2014
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I am pleased to offer five levels of Open Badges as rewards for contributing computing power to the Folding@home project at http://folding.stanford.edu/, which enables anyone in the world to devote computational resources to protein-folding simulations that help advance the fight against a multitude of diseases – such as Alzheimer’s Disease, Parkinson’s Disease, and many cancers. The Longevity Meme Folding@home team seeks to promote increased participation in Folding@home as one way to combat disease and help dramatically lengthen human lifespans within our lifetimes, with the goal of enabling humans to live lives without any upper limit.

These badges were designed by the artist and illustrator Wendy Stolyarov and is issued by  The Rational Argumentator, in conjunction with LongeCity and the Longevity Meme Folding@home team.

You can store these digital badges and share them via Mozilla Backpack to display your achievements to others. The following are the qualifying criteria for each badge:

● Level 1: 5,000 points earned on Folding@home;

● Level 2: 10,000 points earned on Folding@home;

● Level 3: 50,000 points earned on Folding@home;

● Level 4: 100,000 points earned on Folding@home;

● Level 5: 500,000 points earned on Folding@home.

To request a badge, simply send an e-mail to gennadystolyarovii@gmail.com. Include your user name on Folding@home so that your points earned could be verified. You can earn a badge no matter what team you are on, if any, as everyone’s commitment of resources to the protein-folding effort helps the prospects of indefinite life extension. However, you are also encouraged to join The Longevity Meme team in order to help improve its ranking and raise public awareness of the effort life-extension activists are putting into the fight against disease.

Level 1 Folder - Protein Folding for Life Extension

Level 2 Folder - Protein Folding for Life Extension

Level 1 Folder - Protein Folding for Life Extension

Level 4 Folder - Protein Folding for Life Extension

Level 5 Folder - Protein Folding for Life Extension

Life-Extension Activism Opportunities for All – Article by G. Stolyarov II

Life-Extension Activism Opportunities for All – Article by G. Stolyarov II

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The New Renaissance Hat
G. Stolyarov II
June 5, 2014
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You do not need to be a biologist or medical doctor to help hasten the arrival of indefinite life extension. An important array of activist endeavors, which are laying the groundwork for the eventual achievement of unlimited lifespans, can be implemented by anybody. They range from giving out books to playing games to simply running one’s computer – all the while making important contributions to scientific progress and the receptiveness of the general culture to the feasibility and desirability of indefinite longevity.

If you want to glimpse the possibilities in 90 seconds, watch my recent video, “What Anyone Can Do to Advance Indefinite Life Extension”.

In this article, I offer a more detailed overview of some immediately available activism options that anyone can pursue. The time commitment involved in each ranges from minimal to modest, but virtually any of them can fit into the schedule of anyone who recognizes the value of this amazing life we have and the importance of prolonging it as far as possible.

Movement for Indefinite Life Extension (MILE)

MILE_Logo
The Movement for Indefinite Life Extension (MILE) is not a formal organization, but rather a coalition of activists working toward the common goal of achieving indefinite lifespans for people alive today. The MILE coordinates projects and shares articles, images, and news stories via its Facebook group – also accessible using the URL http://themile.info. One of the MILE’s major purposes is to raise awareness of the feasibility and desirability of indefinite life extension and to create a critical mass of support for this most vital of goals. The number of “likes” on the MILE Facebook page is a concise indicator of the movement’s reach, and the eventual goal of the MILE is to achieve 8 million likes by July 17, 2017. Following an incremental approach, the MILE seeks to raise its support by an order of magnitude each year. The goal of 800 supporters was readily exceeded prior to July 17, 2013, and the MILE has launched a concerted effort to reach its Year 2 goal of 8,000 supporters by July 17, 2014. Eric Schulke, who spearheads and coordinates the efforts of the MILE, has launched the MILE Year 2 Goal Fundraiser to fund hundreds of dollars of Facebook advertisements that have already shown success in spreading the message of indefinite life extension to new demographics.

I am proud to have contributed resources to run several ads for MILE that incorporate the core message and the cover image of my children’s book Death is Wrong. These MILE/Death is Wrong ads were designed by my wife and illustrator Wendy Stolyarov and are accompanied by the following text:

Death is WRONG.
Together we can fight it.
Join the Movement for Indefinite Life Extension.

Reaper_MILE_Ad_FBDIW_MILE_AdTo help the MILE reach its Year 2 goal, you can start by clicking the “Like” button on the MILE Facebook page. Beyond that, if you would like to contribute to the advertising campaign and even develop your own custom advertisement that conveys the message of indefinite life extension, this would go a long way toward building the critical mass needed to catalyze public support for life-extension research.

Death is Wrong Book Distribution to Children

DIW_HannaAfter the successful conclusion on April 23, 2014, of my Indiegogo fundraiser to spread over 1,000 copies of the illustrated children’s book Death is Wrong to kids, free of cost to them, I have worked assiduously to coordinate a worldwide distribution effort. Already, 644 out of the 1,029 total available books have been sent to longevity activists throughout the world. Countries where the books have been shipped thus far include the United States, Canada, Mexico, the United Kingdom, the Netherlands, Poland, India, Indonesia, and Singapore. Tens of dedicated longevity supporters have already come forward to request absolutely free shipments of books, but we need more activists to help us distribute the remaining 385 books in their local areas.

Recipients have wide discretion to use their creativity in how to offer the Death is Wrong books to children, as long as the books are made available free of cost and are not resold. Books may be given away to kids directly, lent to multiple kids, given to schools and libraries that will accept them, or used at public readings – among possible other options.

The early successes of the book-distribution effort are among the most heartening and encouraging developments I have observed. Here are some photographs that longevity activists have sent in of their book shipments.

DIW_Amechazurra_ShipmentDIW_Books_Received_CvdB_3
DIW_Books_Received

Here is a charming interview by Aleksander Kelley of his sister Hanna, who is spreading Death is Wrong to the kids she knows.

Help make future scenes like this happen. Requesting a shipment of Death is Wrong books is simple. Send me an e-mail to gennadystolyarovii@gmail.com with (i) your name, (ii) your mailing address, (iii) your statement of support for indefinite life extension, (iv) the number of copies of Death is Wrong requested, and (v) your plan for spreading the books to children, free of cost to them.

Once the shipments arrive, any additional images and videos of the books and events at which they are shared would be most welcome. They can help spread the message of indefinite life extension even further and show the world that the momentum for this cause continues to grow.

Distributed Computing for Medical Science

Would you like to help cure cancer, Alzheimer’s disease, Huntington’s disease, and other deadly ailments, just by running your computer? Most people’s computers spend much time absolutely idle; how about putting that idle time to good use, at minimal additional cost? Distributed computing initiatives such as Folding@home, Rosetta@home, and World Community Grid are absolutely free to join. You just need to download a program that runs the calculations involved in protein-folding simulations and other research efforts while you are not using your computer. Already, these distributed computing initiatives have led to several major medical research breakthroughs, such as this one by Chiba Cancer Center in Japan, which has identified seven drug candidates in the fight against childhood cancer. You can read more about the applications of protein-folding simulations to disease research in this brief post by David Baker of the University of Washington.

While no single medical breakthrough will achieve indefinite lifespans yet, every victory against death and diseases will help us approach that goal. The more of us survive the common killers of our time, the more of us stand a chance of personally witnessing the arrival of longevity escape velocity.

As an additional way to raise the profile of the ideas of indefinite life extension, it is recommended to join a distributed-computing team that explicitly embraces the struggle against senescence and death. On Folding@home, The Longevity Meme team has been folding for years and is ranked 156th out of 220,186 teams as of June 5, 2014. I am spearheading a collaborative effort between The Longevity Meme team, LongeCity, and my online magzine – The Rational Argumentator – to attract renewed participation in Folding@home and The Longevity Meme team among longevity advocates. To provide an additional incentive to join, I am offering a series of five Protein Folding for Life Extension Open Badges, designed by Wendy Stolyarov and available via Badg.us.

FaH-Square-L1 FaH-Square-L2 FaH-Square-L3 FaH-Square-L4 FaH-Square-L5These are badges that you can store and share via Mozilla Backpack to share your achievements with others. The following are the qualifying criteria for each badge:

● Level 1: 5,000 points earned on Folding@home;

● Level 2: 10,000 points earned on Folding@home;

● Level 3: 50,000 points earned on Folding@home;

● Level 4: 100,000 points earned on Folding@home;

● Level 5: 500,000 points earned on Folding@home.

To request a badge, simply send an e-mail to gennadystolyarovii@gmail.com. Include your user name on Folding@home so that your points earned could be verified. You can earn a badge no matter what team you are on, if any, as everyone’s commitment of resources to the protein-folding effort helps the prospects of indefinite life extension. However, you are also encouraged to join The Longevity Meme team in order to help improve its ranking and raise public awareness of the effort life-extension activists are putting into the fight against disease.

On Rosetta@home, the LongeCity team explicitly embraces the ideas of indefinite life extension. On World Community Grid, the Endthedisease team supports life extension and has been involved in numerous disease-fighting computational efforts since 2007. Later this year, the Endthedisease team is anticipated to begin running contests with prizes for top contributors.

Games to Fight Disease

By flying a spaceship through an asteroid field in a computer game, you can help cancer researchers analyze data at a much faster rate than they could before. Play to Cure: Genes in Space is a mobile game released by Cancer Research UK, which anyone with a tablet or mobile phone can play for free. The stated aim of this game is to hasten the day when all cancers are cured – which is, incidentally, the key objective of one of the seven prongs of Dr. Aubrey de Grey’s SENS approach; Dr. de Grey has emphasized that cancer is by far the predominant way by which age-related nuclear mutations harm us.

You can read about the mechanics of and science behind Play to Cure here and watch this video introduction to the game.

Foldit is another free game that enthusiasts of life-extension research can play in order to add the human touch to protein-folding simulations. In 2011, Foldit players discovered the protein structure of a retroviral protease of the Mason-Pfizer monkey virus, an AIDS-like disease in monkeys.

See this list from the Citizen Science Center for more possibilities regarding games you could play and simultaneously participate in innovative citizen-science initiatives – including many devoted to the fight against disease. Games hold out the promise of enabling monumental contributions to scientific research by the general public. A game designed to be sufficiently engaging could attract thousands of non-scientists to do the work that research scientists could conceivably outsource in order to accelerate the rate at which certain kinds of data analysis are performed. The more quickly scientists can iterate through their experiments as a result, the sooner the cures to major diseases will arrive.

Conclusion

Of course, I would urge all life-extension supporters to donate even modest amounts of money to research and advocacy organizations such as the SENS Research Foundation and the Methuselah Foundation, as well as crowdfunded life-extension research projects that are being undertaken with increasing frequency. Yet, I hope that this overview has led readers to recognize that much can be done in addition to monetary donations. Integrate the active pursuit of indefinite longevity into your life, and you will continue to find easy but extremely important ways to become part of the solution to the most pressing problem of all time. Through our efforts, we will hopefully someday be able to celebrate humankind’s greatest victories in the fight against our mutual enemy: death.

Extending Life in Mice With Artificially Shortened Life Spans is Rarely Directly Relevant or Useful – Article by Reason

Extending Life in Mice With Artificially Shortened Life Spans is Rarely Directly Relevant or Useful – Article by Reason

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The New Renaissance Hat
Reason
May 4, 2014
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There are numerous examples of studies that use mice genetically engineered to suffer forms of shortened life span with the appearance of accelerated aging. One has to be very cautious in reading anything into this sort of work, however: it is rarely of any great relevance to normal aging, as it creates and then attempts to ameliorate an entirely artificial situation. The appearance of accelerated aging is not in fact accelerated aging, but is rather often caused by mechanisms that are of little importance in normal aging. Even when the mechanisms are relevant, the overall metabolic circumstances can render it impossible to determine whether or not a partial treatment will be of any use in normal aging. The gold standard for relevance when evaluating new methods is the extension of life in unmodified mice, but unfortunately this is expensive and slow.

The publicity materials quoted below are a good example of research in animals exhibiting shortened life spans. Here scientists are investigating a protein involved in the induction of cellular senescence. As is often the case, however, from the structure of the work it is impossible to tell whether or not their drug candidate will be of any use as a treatment to lower levels of cellular senescence in normal aging and thus produce benefits such as extended health and life span. Those tests will still have occur:

Quote:

When cells or tissue age – called senescence – they lose the ability to regenerate and secrete certain proteins, like a distinctive fingerprint. One of those proteins, PAI-1 (plasminogen activator inhibitor) has been [a focus of] research, originally as it relates to cardiovascular disease. “We made the intellectual leap between a marker of senescence and physiological aging. We asked is this marker for cell aging one of the drivers or mechanisms of rapid physiological aging?”

For the study, [researchers] used mice bred to be deficient in a gene (Klotho) that suppresses aging. These mice exhibit accelerated aging in the form of arteriosclerosis, neurodegeneration, osteoporosis and emphysema and have much shorter life spans than regular mice. [These] rapidly aging mice produce increased levels of PAI-1 in their blood and tissue.

Then scientists fed the rapidly aging mice TM5441 – the experimental drug – in their food every day. The result was a decrease in PAI-1 activity, which quadrupled the mice’s life span and kept their organs healthy and functioning. “This is a completely different target and different drug than anything else being investigated for potential effects in prolonging life. It makes sense that this might be one component of a cocktail of drugs or supplements that a person might take in the future to extend their healthy life.”

Link: http://www.northwestern.edu/newscenter/stories/2014/04/experimental-drug-prolongs-life

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
***

This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

To Accept Aging and Death is to Choose Aging and Death – Article by Reason

To Accept Aging and Death is to Choose Aging and Death – Article by Reason

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The New Renaissance Hat
Reason
April 1, 2014
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It is in the nature of things for people to become more accepting of the imperfect state of the world and the flawed human condition with advancing age, to lose that youthful indignation and urge to change all that causes suffering and injustice. We can blame a range of things for this, but I suspect that it has a lot to do with the growth in wealth and connections that occurs over the years for most individuals. Whatever your starting level, on average the 50-year-old you will be in a better place than the 20-year-old you. The gains you have amassed merge with nostalgia in a slow erosion of the desire to tear down walls and shake up your neighbors: things are better for you, and isn’t that a good thing? Not everyone is this way, of course, but it is a dynamic to be aware of in your relationship with the world. It is human nature to measure today against yesterday, and feel good about gains that are relatively large but absolutely small.

Acceptance of death and aging is the mindset I am thinking in particular here. The unpleasant ends of life are dim and distant myths when you are young and vigorous in your search for world-changing causes. It is the rare young individual who is willing to devote his or her life in preparation for a time half a century down the road. The older folk who feel the pressures of time and encroaching frailty are those who have become more accepting, however. To fight aging and work on rejuvenation treatments is an intrinsically hard sell in comparison to many other ventures. The youth think they have time to focus on other matters first, and the old have come to terms.

Nonetheless, with rapid progress in biotechnology year after year the number of people needed to get the job done is falling rapidly. Ten million supporters willing to put in a little time or money (rather than just a wave and a good word) and the careers of a few thousand scientists and biotechnicians is probably more than is needed at this point, a level of support that lies in a similar ballpark to that of the cancer or stem-cell research communities. We are not there yet, though support for scientific, medical approaches to the treatment and prevention of aging has grown in a very encouraging fashion over the past decade. At any time in the next year or so you might see mainstream press articles in noted publications favorably mention the SENS Research Foundation, regenerative medicine, Google’s Calico initiative, and progress in genetic science all in the same few paragraphs.

We are here, where we are, precisely because numerous people retained a youthful fire and verve, and indignation and horror of aging and death. Despite the ever-present opposition from a mainstream that once mocked aging research, these iconoclasts put in the work that has raised funds, created organizations, and changed minds: all seeds for tomorrow’s grand rejuvenation research community. This is a work in progress. But let us take a moment to admire some of the fire from those driving things along at the grassroots level:

Those Critical of Indefinite Life Extension Fear Life

Quote:

Accepting death is in fact choosing it. In the face of recent discoveries and progress in science, medicine, technology – it is a matter of choice. Pretending to be fearless in the face of death isn’t some form of heroism. It isn’t reasonable or courageous. It is quite the opposite. It is taking the easy way out. Let’s repeat it – death really is the easy way out. You fall asleep; you get a bullet; cancer kills you; some choose suicide; some accept aging and its effects as an inexorable given. The hard truth here that we should be prepared to acknowledge is: accepting death is the true cowardice, no matter the circumstances. Fighting it and choosing life is the true courage.

Critics of indefinite life extension, don’t put on a snide, condescending face and tell me that you aren’t afraid of death, because you are, too.

By your own knee-jerk flippancy, reactionary admission, you are also afraid of life. You’re afraid of death, and you’re afraid of life. You say, right to us, all the time, that you don’t want to bear to deal with the drastic changes, you don’t want to live without all your friends and family around, you don’t want to live with war still being a reality anywhere. You can’t stand all the jerks and the dangerous people, and rich people, or tyrants, controlling you for one decade longer than a traditional lifespan. The thought of it makes you want to jump into your grave right now to get away from this big, bad, scary life.

You, my friend, are afraid of life. Living scares you. You think of life and you cower. You see the challenges of life and you’re too scared to face them. You wouldn’t dare form and join teams and initiatives to meet those challenges on the intellectual combat fields of dialectics and action. You don’t have what it takes. Life isn’t for you. It’s not your thing. So love your death, fear your life. Do that if that’s what you want.

I am afraid of death. It scares me to think of losing my life. I value my life. I have no shame in that. That is the reasonable thing to do. What I have shame for is that anybody would think that being afraid of death might possibly be something to mock.

You mock us for being afraid of death. We are afraid of death; it’s a logical and positive thing to be afraid in the face of it. It reminds a person to take action against danger. It’s your being afraid of life that is to be mocked. So stand up and tell us how afraid you are of living. We promise not to look upon you with too much shame, and we promise to lend you a hand if you need help crossing over to the land of reason.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

Weak Evidence Against a Significant Role for Nuclear DNA Damage in Aging – Article by Reason

Weak Evidence Against a Significant Role for Nuclear DNA Damage in Aging – Article by Reason

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The New Renaissance Hat
Reason
February 2, 2014
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The nuclear DNA in our cells is surrounded by a panoply of exceedingly efficient quality control and repair machinery, but nonetheless damage occurs: individual cells suffer all sorts of mutations over time as molecules react with DNA or pieces are lost or reshuffled during replication. This is more pronounced in long-lived cells, such as those in the central nervous system, or the stem cell populations that support specific tissues.

Cancer spawns from nuclear DNA damage, and the risk of cancer grows greatly with age – not just because of growing damage to nuclear DNA, but also due to the decline of the immune system’s watchdogs and other related consequences of aging. But aside from cancer, does the accumulation of various forms of nuclear DNA damage scattered across our cells contribute meaningfully to dysfunction and decline? There is some debate on this topic, and while the consensus position is more or less “yes, of course,” there is at this point no experiment by which one can conclusively demonstrate that this is the case.

Today I’ll point you to an open-access study in which researchers compare DNA sequencing data from the blood of a pair of 40-year-old twins and a pair of 100-year old twins. Blood cells cycle into and out of circulation on a timescale of a few months, but we might take nuclear DNA damage in blood cells as being representative of the damage present in the population of hematopoietic stem cells that generated those blood cells.

Aging as Accelerated Accumulation of Somatic Variants: Whole-Genome Sequencing of Centenarian and Middle-Aged Monozygotic Twin Pairs

Quote:

It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories.In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing.

We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood.

I would have expected more differences and larger differences to turn up, but, as the researchers note, it is impossible to detect mutations that have not spread to at least some degree. (In this case, that means spreading through the population of hematopoietic stem cells.) A next step might be a survey of whole-genome sequencing by tissue types in old twins, especially those with longer-lived cells, to see whether this low level of exhibited mutational damage is peculiar to blood or typical for most or all tissues.

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The number of somatic variants may be substantially larger but those present in smaller fractions of cells go undetected. Consistent, detectable somatic variation likely includes somatic mosaicism in blood generated during development or clonal expansion of mutations generated at any point during the lifetime. The frequency of these variants is limited in blood even after 100 years of life. In summary, this study shows that the number of detectable somatic variants in blood by using NGS is very low and that accumulation of somatic mutations is not necessarily a consequence of a century of life. Stochastic somatic variation occurring in less than 20% of cells will go undetected, however.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

More Recent Coverage of SENS Research – Article by Reason

More Recent Coverage of SENS Research – Article by Reason

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The New Renaissance Hat
Reason
January 31, 2014
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SENS stands for the Strategies for Engineered Negligible Senescence, a research and development plan first assembled more than a decade ago by biomedical gerontologist Aubrey de Grey. This was a work of vision and synthesis: taking decades of research results from many diverse fields of medical research whose scientists had comparatively little contact with one another, and little interest in working on ways to treat aging, and pulling these results together into a convincing argument as to (a) which forms of cellular and molecular damage cause aging, and (b) how to go about developing the means of repair for this damage.

Aging is damage, and repair is rejuvenation. Sufficiently comprehensive implementations of SENS should not only prevent aging and age-related disease, but also reverse the effects of aging in the old. This isn’t a matter of hand-waving: the capabilities in molecular biology and research plans to build therapies are outlined in considerable detail at the SENS Research Foundation website and in related scientific papers. You should take a look if you haven’t recently. The estimated cost of developing this to the point of demonstration in mice is on a par with the total cost of development of a single drug: perhaps $1-2 billion over 10-20 years.

It is pleasing to chart the changing character of press coverage over the years for SENS rejuvenation research and its figurehead advocate and organizer Aubrey de Grey. In the past ten years of increasing support within the scientific community and an influx of millions of dollars in philanthropic funding for research, it has become ever harder for journalists to stick their heads in the sand and pretend that SENS is either fringe or not real science. The gatekeepers of the establishment are never kind to any form of change or progress in the early days.

Measured by budget the SENS Research Foundation is a presently a tenth of the size of the well-established and mainstream Buck Institute for Aging Research. This is still larger than a good many labs in the field, and funding for SENS research has grown considerably over the past few years. Skilled molecular biologists in numerous laboratories are working on aspects of the SENS program of development for rejuvenation therapies. This work is still at the level of building tools and foundations for later progress, but it is very much real, tangible medical research. This is a new and upcoming field, the future of medical science and aging.

Aubrey de Grey: Out to Defy Death

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Spend a moment asking yourself, “What is the world’s worst problem?”

Biomedical gerontologist Aubrey de Grey, Ph.D., has an answer that may be radically different from yours. For him, it’s aging, and he not only makes a convincing case for why this is so, but he’s devoting his life to doing something about it. Dr. de Grey is the founder of SENS, a research foundation that aims to help build the regenerative medicine industry, an industry that arguably has the best chance for curing the diseases of aging. Surprisingly, he’s having more success than the people who were calling him a maverick and a heretic five years ago ever imagined.

First they ignore you, then they laugh at you, then they fight you, then you win. To my eyes, things have made it to the early stages of the winning part of that saying these days, certainly insofar as the scientific community is concerned. (Much more remains to be done in order to sell the public on the idea that radical life extension is a real possibility and that the relevant research is important and should be supported.) SENS is far more than Aubrey de Grey nowadays: it’s his vision, but has grown to be shared quite widely. There are dozens of influential allied scientists and laboratories, a number of high-net-worth philanthropists providing support, many advocates, a SENS Research Foundation staff, fundraisers, and, of course, the numerous researchers working to build the tools needed for future rejuvenation treatments.

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The SENS Foundation is a public charity based in California, and its purpose is to fill a niche in the research funding chain. Private sector research, particularly in the drug industry, has funds to drive important research, but only after it’s clear that the odds of success are good, the time frame is reasonably short, and the potential for profit large. At the other end of the research spectrum, public sector research funding is available for basic research that doesn’t have an immediate commercial purpose.

However, in Dr. de Grey’s view, and his colleagues’ as well, there’s a midway point between the private sector funding and the public sector, and this midpoint is often neglected. Research that may yield incalculable commercial success (and public benefit as well), may be at such an early stage of development that it doesn’t yet attract commercial funders. “We exist to make sure that this kind of intermediate research is not neglected,” he says.

People no longer refer to Aubrey de Grey as a “maverick” or “heretic.” “These days, I’m more often called ‘controversial,'” he says, sounding pleased with this new characterization.

“Controversial,” after all can be translated as, “might be right.”

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

Gennady and Wendy Stolyarov’s Forthcoming Presentation on “Death is Wrong” at Transhuman Visions 2.0

Gennady and Wendy Stolyarov’s Forthcoming Presentation on “Death is Wrong” at Transhuman Visions 2.0

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I invite all of my readers to join me at the Transhuman Visions 2.0 East Bay conference in Piedmont, CA, on Saturday, March 1, 2014. I will be there with my wife Wendy Stolyarov to deliver the opening presentation about Death is Wrong, our new ambitious illustrated children’s book on indefinite life extension. For a prelude to my presentation, I invite you to read my article, “Why I Wrote a Children’s Book on Indefinite Life Extension“. Also, autographed copies of Death is Wrong will be available for sale.

The Transhuman Visions 2.0 East Bay conference is produced by the Brighter Brains Institute and its energetic, prolific, and creative founder, Hank Pellissier. For detailed information about the conference, see the official Brighter Brains Institute page here.

The poster for this event was designed by none other than Wendy Stolyarov. It is a testament to her skill in graphic design and the new standard of excellence her art brings to the transhumanist movement.

Transhuman Visions 2.0 East Bay – Poster by Wendy Stolyarov
Advancing Pharmaceutical and Medical Technology Does Not Depend on Patents – Article by Nathan Nicolaisen

Advancing Pharmaceutical and Medical Technology Does Not Depend on Patents – Article by Nathan Nicolaisen

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The New Renaissance Hat
Nathan Nicolaisen
January 1, 2014
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Pharmaceutical drug manufacturers are often regarded as the successes of the intellectual property regime. It is assumed that their willingness to take risks by investing heavily in R&D is justified by the awarding of patents over their lifesaving discoveries. Proponents of intellectual property claim that without patents many lifesaving drugs would not exist. They assert that generic drug manufacturers would diminish profit margins and dissipate the original manufacturer’s market share and innovation would come to a virtual standstill. Further, manufacturers once willing to create new drugs will no longer do so without sufficient returns on investment. Research into the matter suggests, however, that patent protection may not be required for medical advances.

Unpatented Medical Technologies

The notion that unpatented medical technologies are not feasible is historically false. Surveys of important medical breakthroughs provide insight into whether patents are absolutely necessary and conducive to innovation in medicine. In 2006, the British Medical Journal challenged its readership to submit a list of the most noteworthy medical and pharmaceutical inventions throughout history. The original list contained over 70 different discoveries before being narrowed down to 15. The list goes as follows in no particular order: penicillin, x-rays, tissue culture, ether anesthetic, chlorpromazine, public sanitation, germ theory, evidence-based medicine, vaccines, the pill, computers, oral rehydration therapy, DNA structure, monoclonal antibody technology, and smoking health risk. Of these discoveries, only two of them have remotely anything to do with patents, chlorpromazine and the pill.[1] In another survey conducted by the United States Centers for Disease Control the results are strikingly similar. Of the ten most important medical discoveries of the twentieth century, none of them had anything to do with patents.[2]

Natural Market Advantages and Trade Secrecy

Contrary to popular belief, large pharmaceutical companies may maintain significant market share advantages after the introduction of generics through the help of natural barriers to entry. Large pharmaceutical companies have a first-mover advantage and an established internal and external structure that competitors, large and small, do not. Regardless of how fast competitors can manufacture a generic drug (never mind the fact that they must hire new labor, train new employees, buy raw materials, establish suppliers, organize logistics, create a marketing and advertising plan, and set up competitive shelf space), it can be extremely difficult to make a dent in the market dominance of an already-established drug. Competition data from India suggests that it takes approximately four years for generic drugs to enter the market.[3] In addition, the Congressional Budget Office calculated that an original drug manufacturer could still maintain a market share of more than 20 percent after the introduction of generics. Expanding the scope of research beyond pharmaceutical drugs, a survey of R&D labs and company managers revealed that between 23 percent and 35 percent believe a patent is an effective way of getting a return on investment. At the same time 51 percent believe trade secrets to be an effective way of ensuring returns.[4]

The Truth about R&D Costs and Generic Drugs

Pharmaceutical drug manufacturers enjoy large margins in spite of large R&D. The claim that R&D for pharmaceuticals is high is not unfounded. The cost to bring a new drug to market varies between estimates of $402 million on the lower end and $800 million on the upper end.[5],[6] Regardless of high R&D costs, drug companies still command high margins. For the past two decades pharmaceutical drugs have been one of the most profitable industries in the United States, never dropping below third place.[7] The profitability of pharmaceuticals can be explained away under the assumption that people are living longer and consuming more pharmaceutical drugs. It may also be suggested that the human population is less healthy than in the past and the demand for pharmaceutical drugs is inelastic. But, analysis of the profit margin on pharmaceutical drugs and lack of any serious innovation suggests that this is not always the case.

The pharmaceutical industry globally maintains about a 25 percent operating margin as opposed to 15 percent for consumer goods. In the United States, this number achieved its zenith at almost 35 percent. The high margin on the drugs may not be due directly to high R&D costs, either. As of 2006, the ratio of R&D to sales revenue was about 0.19.[8] Further, the top 30 pharmaceutical firms in the world incur costs for promotions and advertising that are nearly double the costs of R&D. This is not to imply that there is a perfect amount of R&D spending each firm must do, rather it is to show that the inability to recoup R&D costs is greatly exaggerated.

Generic drugs are not just manufactured by small companies that seek to ride on the coattails of the giants. It is believed that generics add nothing innovative to the realm of lifesaving drugs, they merely manufacture competing drugs that are already in the public domain; the real innovation comes from the companies willing to invest in research and development. The National Institute of Health Care Management conducted a survey of drugs that received approval from the FDA from 1989 to 2000 with revealing results. Just over half the drugs in the survey, 54 percent, were using active ingredients that were already in use in the market. Of the drugs that were approved by the FDA, 23 percent were given a priority rating on the basis that they were a sufficient clinical improvement compared to existing alternatives. As a corollary, 77 percent of the approved drugs did not exhibit any kind of significant clinical improvement.[9] In other words, these drugs are functionally generic drugs, offering no kind of advantage over existing treatments. Large drug companies are ironically engaging in the kind of behavior they abhor by developing functionally generic drugs while wasting valuable R&D resources.

Conclusion

In a truly free market, whoever has the resources to manufacture an invention is permitted to do so, and the firms that enter the market first with a new drug enjoy a significant advantage. Moreover, the fact remains that the best way to protect an idea is to keep it a secret, which is why the trade-secret method remains effective. The federal government, however, has made it profitable to conclude that the best way to protect an idea is twisting the wrists and shoulders of one’s competitors with government force. Yet in spite of overwhelming federal-government intervention, innovation and ingenuity prevail, even if to a lesser degree.

Nathan Nicolaisen is a senior at Luther College in Decorah, Iowa studying business management and mathematics. 

This article was published on Mises.org and may be freely distributed, subject to a Creative Commons Attribution United States License, which requires that credit be given to the author.

Notes

[1] This means that the inventions were not patented, due to some previous patent, or discovered out of desire to obtain a patent. Michele Boldrin and David K. Levine, Against Intellectual Monopoly, (Cambridge University Press, January 2010), 258, 259.

[2] ibid, 259.

[3] ibid, 266

[4] ibid, 186

[5] $402 million is in 2000 dollars. James Bessen and Michael J. Meurer, Of Patents and Property, Boston University Shool of Law, 2008), http://object.cato.org/sites/cato.org/files/serials/files/regulation/2008/11/v31n4-4.pdf

[6] $800 million is in 2000 dollars. Michele Boldrin and David K. Levine, Against Intellectual Monopoly, (Cambridge University Press, January 2010), 241.

[7] ibid, 256

[8] ibid, 255

[9] ibid, 261