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Updates on a Crowdfunded Mouse Lifespan Study – Article by Reason

Updates on a Crowdfunded Mouse Lifespan Study – Article by Reason

The New Renaissance Hat
Reason
January 3, 2015
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For all that I think it isn’t an efficient path forward, one likely to produce meaningful results in moving the needle on human life spans, there is considerable interest in testing combinations of existing drugs and various dietary compounds in mice to see if healthy life is extended. I expect that as public interest grows in the prospects for aging research to move from being an investigative to an interventional field, wherein researchers are actively trying to treat aging, we’ll only see more of this. There is certainly a sizable portion of the research community who think that the the best path ahead is in fact the pharmaceutical path of drug discovery in search of ways to slightly slow the aging process. To their eyes slightly slowing the aging process is all that is plausible, and adding five healthy years to life by 2035 would be a grand success. Google’s Calico initiative looks set to take that path, for example, which I is why I’m not all that hopeful it will produce meaningful results in terms of healthy years gained and ways to help the old suffer less.

There is a considerable overlap between researchers aiming to gently slow aging via drug discovery and researchers whose primary motivation is still investigation, not intervention: to produce a complete catalog of metabolism and how it changes with age, and it’s someone else’s problem to actually use that data. So we have, for example, the Interventions Testing Program at the NIA. This program was long fought for by researchers tired of the lack of rigor in most mouse life span studies, and the people involved are essentially engaged in replacing a lot of carelessly optimistic past results with the realistic view that very little other than calorie restriction and exercise actually does reliably extend life in mice if you go about the studies carefully. This is good science, but it isn’t the road to extended human life spans: it instead has much more to do with understanding the process of aging at a very detailed level. That task is vast and will take a very long time even in this age of computing and biotechnology.

To my eyes the right way to go is the repair approach: build the biotechnologies needed to repair the forms of cellular and molecular damage produced as a side-effect of the normal operation of metabolism, and which clearly distinguish old tissues from young tissues. If you want rejuvenation of the old, a path to adding decades to healthy life, and to eliminate all age-related disease, then repair is the way to go. Fix the damage, don’t just tinker with the engines of life in ways that might possibly slow down damage accumulation just a little. This strategic direction can allow researchers to largely bypass the great complexity of the progression of aging and focus instead on fixing things that are already well known and well cataloged. But I say this a lot, and will continue to do so until more than just a small fraction of the research community agree with me.

Back to mice and lifespan studies: in this day and age institutional research is far from the only way to get things done. Early-stage research is becoming quite cheap as the tools of biotechnology improve, and the global economy allows quality scientific work to be performed in locations that are lot less expensive than the US or Western Europe. We have crowdfunding, the internet, and a supportive community, which means that any group of ambitious researchers can raise a few tens of thousands of dollars and set an established lab in the Ukraine to running a set of mouse lifespan studies. So that happened back in 2013, and has been ongoing since then despite the present geopolitical issues in that part of the world. It is perhaps worth noting that this is the same group that found no effect on longevity from transfusions of young blood plasma into old mice. The studies mentioned below used pre-aged mice, starting at old age as a way to try to discover effects more rapidly, an approach that is fairly widespread.

I am a little mouse and I want to live longer: updates

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Dear contributors, we wish you a happy New Year! We are sorry to be taken by a very-expected but very time-consuming c60 lifespan study to digest the data in a way to make the long report we had announced. So, for the New Year and in order for you not to wait longer, please find at least the main results so far:

1) 23 months old C57BL6 mice received a mixture of 6 therapies that had already been reported to extend the lifespan of mice: Aspirin; Everolimus (mTOR inhibitor, similar action as rapamycin); Metoprolol (beta blocker); Metformin (anti-diabetic drug); Simvastatin (lowers LDL cholesterol); Ramipril (ACE inhibitor).

The drugs were given in the food, at doses that had been reported to extend lifespan … when taken individually. Some people are given that combination of medicines so we hoped that the drug interaction would not be too damaging, and we had wondered if some lifespan synergy within some of these drugs could lead to an overall high lifespan (e.g. if the different drugs improve different functions). But we observed a lifespan reduction in males and in females.

2) In the food of some remaining females we mixed low doses of 4 medications against cardiovascular conditions: Simvastatin; Thiazide (lowers blood pressure); Losartan potassium (angiotensin receptor blocker, lowers blood pressure); Amlodipine (calcium channel blocker, lowers blood pressure).

The question was: taken at a low-to-medium dose, could these drugs that many aged persons take have some overall preventive effect? We transposed to mice an ongoing polypill clinical trial in the UK, using a basic human-mouse conversion scale. Again, a decrease in lifespan was observed.

3) Adaptations of the first combination of drugs actually extended lifespan!

We started at age 18 months instead of 23 months, reduced the dose (as a function of weight) and gave a) the 6 compounds b) ‘only’ aspirin+metformin+everolimus. The results are to be analysed in greater details as we haven’t analyzed the latest data yet. Also, whatever the refined analysis, we would already like to indicate that it would be good to reproduce the experiment in some other conditions, e.g. hybrid mice; in particular as the mortality rates of these mice was higher than the first series (but in a consistent way that supports the life extending effect).

4) Ongoing C60 experiments

After many difficulties in setting the experiment (cross-border transportation in current geopolitical times, checking absorption in mice/ detecting C60/correct source of C60, administration tried in food and replaced by gavage, training for gavage and various measures) we have transposed the popular lifespan test with c60 fullerenes reported in rats by Baati et al. to mice (CBA strain, common in the lab) and with more animals (N=17 per group). There are three groups (gavage of water, of olive oil, of C60 dissolved in olive oil), there are … a lot of health measures and a lot of gavage (at the beginnings of the experiment as administrations are first very frequent and then gradually less frequent). Given that the experiment starts with mid-aged animals, the results are expected for the beginning of 2016.

The original C60 results from a few years back were greeted with some skepticism in the research community, given the very large size of the effect claimed and the small number of animals tested. There was, I think, also a certain annoyance: now that someone had made what was on the face of it an unlikely claim of significant lifespan extension via administration of C60, then some other group was going to have to waste their time in disproving it. We’ll see how that all turns out, I suppose. This is science as it works in practice.

At some point the broad structural classes of research illustrated by the Interventions Testing Program and this crowdfunded mouse study will meet in the middle, and the process of funding and organizing scientific programs will be a far more complicated, dynamic, and public affair than is presently the case. I think this will be for the better. All that we have we owe to science, and a majority of the public thinks all too little of the work that will determine whether they live in good health or suffer and die a few decades from now. The more they can see what is going on, the better for all of us in the end, I think.

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

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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

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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.

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.

Technological Singularities: An Overview – Video by G. Stolyarov II

Technological Singularities: An Overview – Video by G. Stolyarov II

Mr. Stolyarov explains the basic concept of a technological Singularity and his understanding that humankind has already experienced three such Singularities in the form of the Agricultural, Industrial, and Information Revolutions. The next Singularity will come about due to a convergence of technologies such as artificial intelligence, nanotechnology, and biotechnology (including indefinite life extension).

Indefinite Life Extension is Achievable – Video by G. Stolyarov II

Indefinite Life Extension is Achievable – Video by G. Stolyarov II

Mr. Stolyarov summarizes why indefinite life extension is achievable in our lifetimes, given enough effort, funding, and moral support. He encourages your support for the Movement for Indefinite Life Extension (MILE), which has the goal of increasing awareness of indefinite life extension by an order of magnitude each year.

References
– The Movement for Indefinite Life Extension (MILE) Facebook Page: http://themile.info or https://www.facebook.com/pages/MILE-Movement-for-Indefinite-Life-Extension/197250433628807
– SENS Research Foundation: http://sens.org
– Resources on Indefinite Life Extension (RILE): http://rationalargumentator.com/RILE.html

Get Your “Supporter of Indefinite Life Extension” Open Badge

Get Your “Supporter of Indefinite Life Extension” Open Badge

The Rational Argumentator is now offering a free Open Badge to any individual who supports the concept of indefinite human life extension. To claim the badge, click here.

This badge was designed by Wendy Stolyarov, whose art you can see here, here, and here.

If you would like to find out more about Open Badges and the empowering role they can have in producing a new Age of Enlightenment, read this essay.

You would need a free account with Mozilla Backpack to receive the badge. And, of course, you would need to think that indefinite human life extension is desirable. That is all!

You would receive the badge for being a supporter of extending human lifespans beyond any fixed limit. Indefinite human life extension includes the defeat of senescence and other diseases, and the achievement of indefinite youthfulness. While indefinite life extension would not make people indestructible and would not eradicate all causes of death, it would nonetheless lift the “inevitable” death sentence that currently hangs over us all.  Indefinite life extension could be achieved in the future through advances in medical technology, including biotechnology, nanotechnology, and information technology.

Even thinking favorably of indefinite life extension is a courageous, forward-thinking, and highly beneficial attitude to take. Enjoy your reward!

Announcements and October-November 2012 Update to Resources on Indefinite Life Extension

Announcements and October-November 2012 Update to Resources on Indefinite Life Extension

I expect be unavailable to publish The Rational Argumentator until circa November 22, 2012 – but, in the meantime, various new offerings have been posted for my readers.

In addition, I have recently been impressed by the significant contributions my computer has made to the World Community Grid Help Conquer Cancer distributed computing project. (You can see a presentation by one of the project’s lead scientists, Dr. Igor Jurisica, here.) About a month ago, the Help Conquer Cancer project was enhanced to allow computers’ Graphics Processing Units (GPUs) to assist in the analysis of millions of experiments. My own recently enhanced computer has been participating heavily, which caused my worldwide ranking on World Community Grid to rise within a month from about 60,000th place to 26,744th place (updated every half-day) in terms of credits and 15,795th place in terms of results returned. In addition, for the totality of BOINC distributed computing projects, I have risen to the 98.2932nd percentile and a world rank of 42,446 in terms of total credits and the 99.5634th percentile and a world rank of 10,878 in terms of recent average credit. In the United States, I am ranked at 11,802nd place in terms of total BOINC credit earned.

I expect that my computer will continue to run at full capacity during the upcoming weeks, and indefinitely into the foreseeable future.

For your contemplation and enjoyment, I offer here the list of diverse and fascinating articles and videos that have been included in the Resources on Indefinite Life Extension (RILE) page in October and early November of this year.

Articles

– “Nanoparticles Against Aging” – Science Daily and Asociación RUVID – October 3, 2012

– “Nanoparticles can deliver antiaging therapies” – Brian Wang – The Next Big Future – October 4, 2012

– “A Speculative Order of Arrival for Important Rejuvenation Therapies” – Reason – Fight Aging! – October 4, 2012

– “Therapy will use stem cells to heal heart” – Pauline Tam – October 4, 2012

– “Aubrey de Grey on Longevity Science” – Reason – Fight Aging! – October 5, 2012

– “Predicted sequence of Antiaging rejuvenation” – Brian Wang – The Next Big Future – October 5, 2012

– “Researchers use magnets to cause programmed cancer cell deaths” – Bob Yirka – October 8, 2012 

– “Lilly Alzheimer’s Drug Slows Mental Decline, Study Finds” – Shannon Pettypiece – October 8, 2012

– “Vitamin Variants Could Combat Cancer as Scientists Unravel B12 Secrets” – ScienceDaily and University of Kent – October 8, 2012

– “Human Immortality: Singularity Summit Looks Forward to the Day That Humans Can Live Forever” – Hamdan Azhar – Policymic – October 2012

– “Drug From Chinese ‘Thunder God Vine’ Slays Tumors in Mice” – Drew Armstrong – Bloomberg – October 17, 2012

– “82 Years of Technology Advances; but best yet to come” – Dick Pelletier – Transhumanity.net – October 25, 2012

– “New you by 2022: biotech enhancements will help you ‘grow young’” – Dick Pelletier – Positive Futurist – October 2012

– “Flu Vaccination May Increase Longevity” – Lyle J. Dennis, M.D. – Extreme Longevity – October 29, 2012

– “Dead as a Doornail?” – Peter Rothman – h+ Magazine – November 1, 2012

– “An Outcast Among Peers Gains Traction on Alzheimer’s Cure” – Jeanne Whalen – Wall Street Journal – November 9, 2012

 

Videos

Anthony Atala
Anthony Atala at TEDMED 2009
January 21, 2010

Ray Kurzweil

From Eliza Watson to Passing the Turing Test – Singularity Summit 2011

October 25, 2011

Nikola Danaylov

Ray Kurzweil on Singularity 1 on 1: Be Who You Would Like to Be – October 13, 2012

A Libertarian Transhumanist Critique of Jeffrey Tucker’s “A Lesson in Mortality” – Audio Essay by G. Stolyarov II, Read by Wendy Stolyarov

A Libertarian Transhumanist Critique of Jeffrey Tucker’s “A Lesson in Mortality” – Audio Essay by G. Stolyarov II, Read by Wendy Stolyarov

Mr. Stolyarov, a libertarian transhumanist, offers a rebuttal to the arguments in Jeffrey Tucker’s 2005 essay, “A Lesson in Mortality“.

This essay is read by Wendy Stolyarov.

As a libertarian transhumanist, Mr. Stolyarov sees the defeat of “inevitable” human mortality as the logical outcome of the intertwined forces of free markets and technological progress – the very forces about which Mr. Tucker writes at length.

Read the text of Mr. Stolyarov’s essay here.
Download the MP3 file of this essay here.
Download a vast compendium of audio essays by Mr. Stolyarov and others at TRA Audio.

References

It’s a Jetsons World – Book by Jeffrey Tucker
– “Without Rejecting IP, Progress is Impossible” – Essay by Jeffrey Tucker – July 18, 2010
– “The Quest for Indefinite Life II: The Seven Deadly Things and Why There Are Only Seven” – Essay by Dr. Aubrey de Grey – July 30, 2004
Resources on Indefinite Life Extension (RILE)
– “How Can I Live Forever?: What Does and Does Not Preserve the Self” – Essay by G. Stolyarov II