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Why Do We Advocate for Rejuvenation Research? – Article by Reason

Why Do We Advocate for Rejuvenation Research? – Article by Reason

The New Renaissance Hat
Reason
November 24, 2014
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Yesterday, I had occasion to spend six hours or so in the emergency room of a medical center largely focused on treating serious conditions that are most prevalent in old people. A part of that experience by necessity involved listening to the comings, goings, and conversations of those present. These are not private places: they are typically divided visually by screens but with no way to avoid overhearing the staff and patients. The people there are generally not too concerned about privacy in the immediate sense in any case, having far more pressing matters to focus upon.

So, by proxy, one gets to experience small and somewhat wrenching slices of other people’s lives. It is very easy for even those who follow aging research and speak up for rejuvenation treatments to forget just how hard it is to be very old. It’s one thing to know about the catalog of pain, suffering, and loss of capabilities, the conditions we’d like to find ways to turn back, and another to watch it in action. It is, really, a terrible thing to be frail.

A fellow was brought in a little while after I arrived, a 90-something man who looked a lot better on the exterior than perhaps your mental picture of a 90-something individual might be. Tall, and surprisingly lacking in wrinkles stretched out on the rolling gurney under blankets, a mess of cables, and an oxygen mask. That he had fallen was what I heard from the conversation of the medics, and was in pain. He cried out several times as he was moved from the gurney. It took some time and care to do it without hurting him more, given his weakness.

He seemed confused at first, but that was just my misperception: you try being 90 and in pain some time and see how well you do while you’re being moved around and told to hold this and let go of that. The fellow answered the bevy of questions the receiving staff had for him, but the thing that caught at me was the time he took with the answers, and the questions he just missed. He was coherent, even quite sharp at times, not on any more painkillers than a handful of Tylenol, as I later heard, but he clearly struggled with something that we younger folk all take for granted: parse the question, find the information, form up a reply and speak it. Cognitive ability in all these areas becomes ever less efficient with old age, and there’s something hollowing about hearing what is clearly a capable guy set back for a dozen seconds by a short question about one of the details of his fall. The medic repeated the question a few times and in different ways, which was clearly just making the information overload worse.

It sticks with you to be the observer in this situation and clearly and suddenly realize that one day that faltering older person will be you, trying and often failing to force your mind into the necessary connections rapidly enough for the younger people around you. I know this, but knowing it and having it reinforced by being there are two very different things. An aged person is no less intelligent, far more experienced, wiser and all the rest, but the damage to the structure of the brain that occurs even in those without dementia means that making use of all of that in the way it deserves is near insurmountable.

The fellow’s 60-something daughter arrived a little later to provide support and fill in more of the details. A story was conveyed in bits and pieces: that he was near blind now, and just about too frail to walk safely, even with a frame. The blindness explained a great deal of what had sounded to my ignorant ears as confusion in the earlier part of the fellow’s arrival: we assume all too many things about those around us, such as the use of sight in an unfamiliar environment, or the ability to walk, or think quickly – and all of this is taken from us by aging. The fellow lived with his wife still, and she was of a similar age to him. His wife was not there because she herself was too frail to be undertaking even a short trip at such short notice. That seemed to me a harsh blow on top of the rest of what old age does to you. At some point you simply cannot do everything you’d want to as a partner. You are on the sidelines and at the point at which your other half is most likely to die, you are most likely unable to be there.

In this case the fellow was in no immediate danger by the sound of it. By good luck this was in no way likely to be a fatal accident, but rather another painful indignity to be endured as a part of the downward spiral of health and ability at the end of life. Once you get to the point at which simply moving from room to room bears a high risk of accident, and this is by no means unusual for a mentally capable person in their 90s, then it really is just a matter of time before you cannot live for yourself with only minimal assistance.

When talking with his daughter while he waited on a doctor and medical assistants to come and go with tests and updates, the fellow was much faster in his responses, though this was interrupted by a series of well-meaning but futile attempts to ease his pain by changing his position, each as much an ordeal as the move from the gurney had been. The conversation between father and daughter had the sense of signposts on well-worn paths, short exchanges that recapitulated the high points of many discussions that had come before. She wanted her father to move into an assisted living facility, and this fall was the latest in a line of examples as to why it was past the time for this – she simply could not provide all of the support needed on her own. She wasn’t even strong enough herself to be able to safely get him back up on his feet after a fall. He was concerned about cost and the difficulties of moving, uncertainties and change. They went back and forth on this for a while. “We have to accept that it’s just going to be more expensive as we get older,” she said at one point, and he replied “I think you’re getting the picture now,” and laughed. There wasn’t much to laugh about, but we can all do it here and there under these circumstances. I believe it helps.

I walked out of there after my six hours of hurry up and wait was done. They were still there, and whenever it is he leaves to go home it is unlikely it will be on his own two feet. But this is a scene I’ll no doubt be revisiting at some point in the future, some decades from now, playing the other role in this small slice of life. What comes around goes around, but I’d like it to be different for me, and more importantly to be different for millions of others a lot sooner than my old age arrives.

Which leads to this: why does Fight Aging! exist? Why do we do this? Why advocate, why raise funds for research programs into ways to treat aging that may take decades to pay off? We do this because we can help to create a future in which there will be no more emergency rooms like the one I visited, no conversations about increasing disability, no pain, and no struggles to answer questions as quickly as one used to. No profound frailty. All these things will be removed by the advent of therapies that can effectively repair the causes of aging, curing and preventing frailty and age-related disease, and the sooner this happens the more people will be spared.

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.

The 2014 Fight Aging! Fundraiser Starts Now: We’ll Match Your Research Donations with $2 for Every $1 Given – Article by Reason

The 2014 Fight Aging! Fundraiser Starts Now: We’ll Match Your Research Donations with $2 for Every $1 Given – Article by Reason

The New Renaissance Hat
Reason
October 4, 2014
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Note from the Editor: The Rational Argumentator strongly supports this matching fundraiser and encourages all readers to donate any sums of money to the SENS Research Foundation, in order to accelerate the basic research into and the development of cures for the debilitating diseases of old age. I personally made a donation of $100 on October 4, 2014, knowing that its impact will be tripled through a 2-for-1 additional contribution by the generous donors who established the matching fund. This is the time to leverage our resources and ensure that this literally vital research gets done as soon as possible. I am grateful to Reason of FightAging.org for his tireless efforts in advocating for life-extension research and spearheading campaigns to attract the funding that this area of science urgently needs.

~ Gennady Stolyarov II, Editor-in-Chief, The Rational Argumentator, October 4, 2014

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It is that time again, and our 2014 matching fundraiser started October 1st 2014. From now until the end of the year, December 31st 2014, we will match the first $50,000 donated to the SENS Research Foundation with $2 for every $1 given. These funds will help to speed progress in ongoing scientific programs conducted in US and European research centers, their ultimate aim being to repair and reverse the causes of frailty and age-related disease.

The SENS Research Foundation is a 501(c)(3) charity and all US donations are tax-deductible. Donations from most European Union countries are also tax-deductible, though the details vary by location. Please contact the SENS Research Foundation to find out more.

The Matching Fund Founders Ask You to Join Us

Who are we? We are Christophe and Dominique Cornuejols, David Gobel of the Methuselah Foundation, Dennis Towne, Håkon Karlsen, philanthropist Jason Hope, Michael Achey, Michael Cooper, and Reason of Fight Aging! We are all long-time supporters of SENS research aimed at rejuvenation through repair of the known root causes of aging. The few types of cellular and molecular damage that accumulate in all of our tissues cause progressive dysfunction and eventual death for everyone – unless something is done to stop it. This cause is important enough for everyone to do their part, and for us that means putting up a $100,000 matching fund we want you to help draw down: for every dollar you donate, we will match it with two of our own.

Even Small Donations Make a Meaningful Difference

Early stage medical biotechnology research of the sort carried out at the SENS Research Foundation costs little nowadays in comparison to the recent past. The cost of tools and techniques in biotechnology has plummeted in the past decade, even while capabilities have greatly increased. A graduate student with $20,000 can accomplish in a few months what would have required a full laboratory, years, and tens of millions of dollars in the 1990s. All of the much-lamented great expense in modern medicine lies in clinical translation, the long and drawn out process of trials, retrials, marketing, and manufacturing that is required to bring a laboratory proof of concept into clinics as a widely available therapy.

The SENS Research Foundation is focused on early stage research, following a plan that leads to technology demonstrations in the laboratory. With a proof of concept rejuvenation therapy the world will beat a path to their doorstep in order to fund clinical translation. The real challenge is here and now, raising the funds to get to that step. A few tens of thousands of dollars means the difference between a significant project delayed indefinitely or that project completed.

To pick one example, last year the community raised $20,000 to fund cutting edge work in allotopic expression of mitochondrial genes, a potential cure for the issue of mitochondrial damage in aging. That was enough to have a skilled young researcher work on the process for two of the thirteen genes of interest over a period of months. It really is that cheap given an existing group like the SENS Research Foundation with diverse connections and access to established laboratories.

Your donations make a real difference.

Spread the Word, Tell Your Friends

Don’t forget to tell your friends about this fundraiser. Talk to your community, online and offline. Consider running local events to help meet our goal of raising $50,000 from a grassroots community of supporters. The more people who know about the prospects for near future therapies resulting from rejuvenation research of the sort carried out by the SENS Research Foundation, the easier it becomes to raise funds and obtain institutional support for these research programs in the future.

Launched at /r/Futurology and in Conjunction with Longevity Day

Take a look at the generous spirit displayed at /r/Futurology, the futurist Reddit community, when given the chance to help. Scores of people there have already donated modest sums to the cause in response to our fundraiser: many thanks to you all!

The 1st of October marks the launch of this fundraiser, but it is also the International Day of Older Persons, and the International Longevity Alliance would like this to become an official Longevity Day. This year, just like last year, groups of futurists around the world will be holding events to mark the occasion, and this includes the scientists and advocates present at the 2014 Eurosymposium on Healthy Aging.

Download the 2014 Fundraiser Posters

The full size graphics here are large enough for 24 x 36 inch posters, but are also suitable for page-sized fliers. The original Photoshop files are available on request, but are a little large to put up here. Make as much use of these as you like – please help to spread the word and help this fundraiser to meet its target.

Color design, 3600 x 5600 pixels suitable for 24 x 36 inch posters, 11.3MB
Color design, 2400 x 3600 pixels suitable for letter size, 6.3MB

Blue design, 7200 x 10800 pixels suitable for 24 x 36 inch posters, 13.1MB
Blue design, 2400 x 3600 pixels suitable for letter size, 3.8MB

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.

Our Cells Will Be Guided and Protected by Machines – Article by Reason

Our Cells Will Be Guided and Protected by Machines – Article by Reason

The New Renaissance Hat
Reason
September 21, 2014
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A gulf presently lies between the nanoscale engineering of materials science on the one hand and the manipulation and understanding of evolved biological machinery on the other. In time that gulf will close: future industries will be capable of producing and controlling entirely artificial machines that integrate with, enhance, or replace our natural biological machines. Meanwhile biologists will be manufacturing ever more artificial and enhanced versions of cellular components, finding ways to make them better: evolution has rarely produced the best design possible for any given circumstance. Both sides will work towards one another and eventually meet in the middle.

Insofar as aging goes, a process of accumulating damage and malfunction in our biology, it is likely that this will first be successfully addressed and brought under medical control by producing various clearly envisaged ways to repair and maintain our cells just as they are: remove the damage, restore youthful function, and repeat as necessary. We stand much closer to that goal than the far more ambitious undertaking of building a better, more resilient, more easily repaired cell – a biology 2.0 if you like. That will happen, however. Our near descendants will be as much artificial as natural, and more capable and healthier for it.

The introduction of machinery to form a new human biology won’t happen all at once, however, and it isn’t entirely a far future prospect. There will be early gains and prototypes, the insertion of simpler types of machine into our cells for specific narrow purposes: sequestering specific proteins or wastes, or as drug factories to produce a compound in response to circumstances, or any one of a number of other similar tasks. If you want to consider nanoparticles or engineered assemblies of proteins capable of simple decision tree operations as machines then this has already happened in the lab:

Researchers Make Important Step Towards Creating Medical Nanorobots

Quote:

Researchers [have] have made an important step towards creating medical nanorobots. They discovered a way of enabling nano- and microparticles to produce logical calculations using a variety of biochemical reactions. Many scientists believe logical operations inside cells or in artificial biomolecular systems to be a way of controlling biological processes and creating full-fledged micro-and nano-robots, which can, for example, deliver drugs on schedule to those tissues where they are needed.

Further, there is a whole branch of cell research that involves finding ways to safely introduce ever larger objects into living cells, such as micrometer-scale constructs. In an age in which the state of the art for engineering computational devices is the creation of 14 nanometer features, there is a lot that might be accomplished in the years ahead with the space contained within a 1000 nanometer diameter sphere.

Introducing Micrometer-Sized Artificial Objects into Live Cells: A Method for Cell-Giant Unilamellar Vesicle Electrofusion

Quote:

Direct introduction of functional objects into living cells is a major topic in biology, medicine, and engineering studies, since such techniques facilitate manipulation of cells and allows one to change their functional properties arbitrarily. In order to introduce various objects into cells, several methods have been developed, for example, endocytosis and macropinocytosis. Nonetheless, the sizes of introducible objects are largely limited: up to several hundred nanometers and a few micrometers in diameter. In addition, the uptake of objects is dependent on cell type, and neither endocytosis nor macropinocytosis occur, for example, in lymphocytes. Even after successful endocytosis, incorporated objects are transported to the endosomes; they are then eventually transferred to the lysosome, in which acidic hydrolases degrade the materials. Hence, these two systems are not particularly suitable for introduction of functionally active molecules and objects.To overcome these obstacles, novel delivery systems have been contrived, such as cationic liposomes and nanomicelles, that are used for gene transfer; yet, only nucleic acids that are limited to a few hundred nanometers in size can be introduced. By employing peptide vectors, comparatively larger materials can be introduced into cells, although the size limit of peptides and beads is approximately 50nm, which is again insufficient for delivery of objects, such as DNA origami and larger functional beads.

Here, we report a method for introducing large objects of up to a micrometer in diameter into cultured mammalian cells by electrofusion of giant unilamellar vesicles (GUVs). We prepared GUVs containing various artificial objects using a water-in-oil emulsion centrifugation method. GUVs and dispersed HeLa cells were exposed to an alternating current (AC) field to induce a linear cell-GUV alignment, and then a direct current (DC) pulse was applied to facilitate transient electrofusion.

With uniformly sized fluorescent beads as size indexes, we successfully and efficiently introduced beads of 1 µm in diameter into living cells along with a plasmid mammalian expression vector. Our electrofusion did not affect cell viability. After the electrofusion, cells proliferated normally until confluence was reached, and the introduced fluorescent beads were inherited during cell division. Analysis by both confocal microscopy and flow cytometry supported these findings. As an alternative approach, we also introduced a designed nanostructure (DNA origami) into live cells. The results we report here represent a milestone for designing artificial symbiosis of functionally active objects (such as micro-machines) in living cells. Moreover, our technique can be used for drug delivery, tissue engineering, and cell manipulation.

Cell machinery will be a burgeoning medical industry of the 2030s, I imagine. To my eyes the greatest challenge in all of this is less the mass production of useful machines per se, and more the coordination and control of a body full of tens of trillions of such machines, perhaps from varied manufacturers, introduced for different goals, and over timescales long in comparison to business cycles and technological progress. That isn’t insurmountable, but it sounds like a much harder problem than those inherent in designing these machines and demonstrating them to be useful in cell cultures. It is a challenge on a scale of complexity that exceeds that of managing our present global communications network by many orders of magnitude. If you’ve been wondering what exactly it is we’ll be doing with the vast computational power available to us in the decades ahead, given that this metric continues to double every 18 months or so, here is one candidate.

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.

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

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.

The Slowly Spreading Realization That Aging Can Be Defeated – Article by Reason

The Slowly Spreading Realization That Aging Can Be Defeated – Article by Reason

The New Renaissance Hat
Reason
May 21, 2014
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At some point in the next ten to twenty years the public at large, consisting of people who pay little attention to the ins and outs of progress in medicine, will start to wake up to realize that much longer healthy lives have become a possibility for the near future. The preliminaries to this grand awakening have been underway for a while, gradually, and will continue that way for a while longer. A few people every day in ordinary walks of life notice that, hey, a lot of scientists are talking about greatly extending human life spans these days, and, oh look, large sums of money are floating around to back this aim. There will be a slow dawning of realization, one floating light bulb at a time, as the concept of radical life extension is shifted in another brain from the “science fiction” bucket to the “science fact” bucket.

Some folk will then go back to what they were doing. Others will catch the fever and become advocates. A tiny few will donate funds in support of research or pressure politicians to do the same. Since we live in an age of pervasive communication, we see this process as it occurs. Many people are all to happy to share their realizations on a regular basis, and in this brave new world everyone can be a publisher in their own right.

Here is an example that I stumbled over today; a fellow with a day-to-day focus in a completely unrelated industry took notice and thought enough of what is going on in aging research to talk about it. He is still skeptical, but not to the point of dismissing the current state and prospects for longevity science out of hand: he can see that this is actionable, important knowledge.

What if de Grey and Kurzweil are half right?

Quote:

I think these guys – and the whole movement to conquer aging – is fascinating. I am highly skeptical of the claims, however. Optimism is all well and good, and I have no off-hand holes to poke in their (very) well-articulated arguments. But at the same time, biology is fiendishly complex, the expectations beyond fantastical.

Still though, I have to wonder: What if guys like de Grey and Kurzweil are half right, or even just partially right? What if, 30 years from now, it becomes physically impossible to tell a 30-year-old from a 70-year-old by physical appearance alone? It sounds nutty. But it’s a lot less nuttier, and a lot closer to the realm of possibility, than living to 1,000 – which, again, some very smart people have taken into their heads as an achievable thing.

People who don’t take care of themselves are insane. Ok, not actually “insane.” But seriously, given the potential rewards AND the risks, not taking care of your body and mind – not treating both with the utmost respect and care – seems absolutely nuts. At the poker table I see these young kids whose bodies are already turning to mush, and a part of me just wants to grab them by the shirt collar and say “Dudes! What the hell is WRONG with you!!!”

If it is possible – just realistically possible, mind you – that I could still be kicking ass and taking names at 125 years old, then I want to be working as hard as I can to preserve and maintain my equipment here and now. No matter what miracles medical science will achieve in future, working from the strongest, healthiest base possible will always improve the potential results, perhaps by an order of magnitude. Individuals who go into old age with fit, healthy bodies and sound minds, and longstanding habits to maintain both, may find potential for extended performance at truly high quality of life that was never before imaginable.

As the foundations of rejuvenation biotechnology are assembled and institutions like the SENS Research Foundation continue to win allies in the research community and beyond, the number of people experiencing this sort of epiphany will grow. The more the better and the sooner the better, as widespread support for the cause of defeating aging through medical science is necessary for more rapid progress: large scale funding always arrives late to the game, attracted by popular sentiment. The faster we get to that point, the greater our chances of living to benefit from the first working rejuvenation treatments.

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.

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

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

More Attention for “Death is Wrong” – Article by Reason

More Attention for “Death is Wrong” – Article by Reason

The New Renaissance Hat
Reason
April 12, 2014
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I like to see advocates setting forth to create small scale initiatives like the children’s book Death is Wrong and the associated fundraiser to distribute copies. At the large scale a broad advocacy movement for a cause in medical research isn’t a monolithic thing; it is made up thousands of such efforts, a tapestry of individual who each thought enough of the cause to stand up and do something about it. More of this is always a good thing, and working towards a cure for degenerative aging is the most worthy of causes that I know of.

Donating to the right sort of cutting edge research is one approach, and the one I favor, but equally we have to get out there and persuade more people to do the same. Money has to come from somewhere. There is always a balance between raising research funding to get the job done versus funding the cost of gathering more supporters and thus making it more likely that greater amounts of research funding can be obtained. Research results help to convince more people to fund more research, but there is never enough support in the early crucial stages – the really large amounts of research funding arrive after the most important work is done, as is the case for every trend.

The starting point for large amounts of future funding and rapid progress towards actual, real, working rejuvenation treatments is some mix of research funding and advocacy initiatives today, however. All such efforts should be encouraged, as it is through them that the longevity science community finds its way to a louder voice in the public sphere, a taller soapbox from which to persuade and educate. Aging is a horror, the greatest cause of pain and suffering in this world of ours, and we stand at the verge of being able to do something about it – but only if many more people come to think that this cause has merit and make their own contributions to help out.

Praise for Death is Wrong, a delicious transhumanist book for children – Review by Guilio Prisco

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Death is a disease, and hopefully future scientists, perhaps including the young readers of the book, will find a cure. Previous generations thought that death is inevitable, and invented delusional fake philosophies to make death easier to accept. This reaction is understandable – if you can’t avoid something, you look for ways to accept it – and explains all usual rhetorical babbling in praise of death: “overpopulation, make room for the young, death is a tool of evolution, boredom after a long life,” and the utterly idiotic “death gives meaning to life.” The book deconstructs all these fake “arguments” and calls them what they are: understandable but pathetic attempts to rationalize the inevitable.

Provocative strong messages get heard, and teaching children that death will be cured is very provocative in today’s dull, defeatist, politically correct cultural climate. I think writing for children forces to keep things clean end simple, without big words and endless caveats, cutting through the noise and getting to the point. Clear, clean, and simple communication focused on the core message, with qualifications and caveats (if they are really needed) in footnotes, is something that transhumanists should practice more, and writing for children is a good way to learn.

Spreading the Word That Death is Wrong

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Who could have thought a month ago that an illustrated children’s book on indefinite life extension would become a fiercely, passionately discussed phenomenon not just in transhumanist and futurist circles, but on mainstream publications and forums? And yet that is exactly what has happened to Death is Wrong – certainly the most influential and provocative of all of my endeavors to date. I am thrilled that it is precisely my pursuit of this most fundamental and precious goal – preservation of the life of every innocent individual – that has achieved greater public exposure, controversy included, than anything else I have ever done.

Review of “Death is Wrong” by Adam Alonzi

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Death can be cured. Let this sink into your brain, not because it is comforting, but because it is true. Even obvious truths will not gain acceptance unless we vigorously campaign against the falsehoods. Death is not something to embrace, and it is not something to ignore. To turn it into a matter of metaphysics or “bioethics” is insulting to those who, by no fault of their own, are burdened by the ailments of old age. There are many extraordinary men and women who could go on working for hundreds of years if their stars were not designed to dim so soon.

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

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

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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.

Theorizing That Some Change in the Aging Brain is Optimization, Not Degeneration – Article by Reason

Theorizing That Some Change in the Aging Brain is Optimization, Not Degeneration – Article by Reason

The New Renaissance Hat
Reason
February 9, 2014
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The nature of neural networks is perhaps better understood by more people nowadays than used to the be the case. Forms of neural network are used for a range of computational purposes, where they have proved useful as a way to economically discover solutions to difficult problems in pattern recognition, optimization, and other fields. How a particular solution works isn’t always clear, especially when using larger networks, but if it can be proven to work well then why worry?

We ourselves are neural networks: the complex adaptive phenomena that we choose to call the self arises from comparatively simple exchanges between many, many neurons. The machine is the connections and the state of its neurons, constantly altering itself in response to circumstances and its own operation.

The brain, like all tissues, suffers due to the accumulation of cellular and molecular damage that drives aging. But which of the characteristic differences between a young brain and an old brain are aging, and which are the expected operation of the neural network as it processes and reprocesses the data gathered throughout life? In some cases the classification is obvious: broken blood vessels and white matter hyperintensities are damage, as is the amyloid that accumulates in Alzheimer’s disease. We would be better off without them, and they harm us by destroying physical structures needed for operation of the brain. Once researchers start looking at the structure of neural connections, or activity in response to stimulus, or gene expression maps in various portions of the brain things become a little less clear, however:

The Brain Ages Optimally to Model Its Environment: Evidence from Sensory Learning over the Adult Lifespan

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The aging brain shows a progressive loss of neuropil, which is accompanied by subtle changes in neuronal plasticity, sensory learning and memory. Neurophysiologically, aging attenuates evoked responses – including the mismatch negativity (MMN). This is accompanied by a shift in cortical responsivity from sensory (posterior) regions to executive (anterior) regions, which has been interpreted as a compensatory response for cognitive decline.

Theoretical neurobiology offers a simpler explanation for all of these effects – from a Bayesian perspective, as the brain is progressively optimized to model its world, its complexity will decrease. A corollary of this complexity reduction is an attenuation of Bayesian updating or sensory learning.

Here we confirmed this hypothesis using magnetoencephalographic recordings of the mismatch negativity elicited in a large cohort of human subjects, in their third to ninth decade. Employing dynamic causal modeling to assay the synaptic mechanisms underlying these non-invasive recordings, we found a selective age-related attenuation of synaptic connectivity changes that underpin rapid sensory learning. In contrast, baseline synaptic connectivity strengths were consistently strong over the decades. Our findings suggest that the lifetime accrual of sensory experience optimizes functional brain architectures to enable efficient and generalizable predictions of the world.

My suspicion is that it would be faster to implement rejuvenation biotechnologies and then assess what happens to an aging brain that remains physiologically young than to fully pick apart and understand present contributions to changes over time in the brain.

This line of research is of interest because of a potential threat to extreme longevity, past the present limits of human life span, once we have build the necessary medical technologies. The threat is this: it is possible that the brain is like the immune system, in that it is poorly structured for long term use, and will fail for reasons inherent to that structure, even in the absence of damage. We have no reason to suspect that this is the case, but equally there is no good reason to rule this out – the scientific community simply doesn’t understand enough about the detailed operation of the brain to say either way with confidence.

On the plus side, this is a comparatively remote potential threat, something that lies decades past all the other fatal forms of damage and age-related disease that we have to deal with. Old people with little physical damage to their brains are sharp and on the ball, to the degree allowed by their failing bodies and decades of increasing caution required in their interaction with the world. Further, by the time we are at the point of worrying about this, biotechnology will be far more advanced. So it is, I think, worth considering, but not worth panicking over.

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.

A Spanish-Language Interview With Aubrey de Grey – Post by Reason

A Spanish-Language Interview With Aubrey de Grey – Post by Reason

The New Renaissance Hat
Reason
February 2, 2014
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SENS Research Foundation cofounder Aubrey de Grey has been in the European press of late – such as the interview quoted below. Automated translation of colloquial Spanish is almost as bad as that of Russian, so proceed with caution. Even so there is much to be said for living in an age in which I can complain about the quality of automated translation: its existence greatly lowers the barriers to ongoing communication between regions of the world.

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Question: My daughter asked me why we die. What should I say?

 

Answer: You can say that the human body is a machine, a very complicated machine, but it should not surprise us that it stops working, because that happens to all machines, including cars. The good news is that cars can last much longer than was planned if given a really good and complete maintenance. That’s why there are cars that are one hundred years old even if they were designed to only last ten or twenty. It should be the same for the human body, and the only reason it does not happen is that our body is so complicated that we have not yet understood how to do that maintenance. But we’re working on it.

Question: So I tell my daughter that she will live a thousand years?

Answer: Of course, we do not know, but I think we have at least 50% chance of developing these maintenance technologies if we collect enough money to support research. In 20 or 25 years we will have therapies that affect people who are then 60 or 70 years old and rejuvenate them to the point of granting an additional 30 years of healthy life. That means they will have another 30 years in which we can build even better therapies and rejuvenate them once again. This is what I call the “escape velocity of aging” and is the reason I think the people who are born now may avoid the problems of being old. That means your longevity depends on the risk of dying from accidents, but not on the date you were born.

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.