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

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

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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?

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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

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

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

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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

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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

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

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

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

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

Those Critical of Indefinite Life Extension Fear Life

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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.

Those Critical of Indefinite Life Extension Fear Life – Article by Eric Schulke and Wioletta Karkucińska

Those Critical of Indefinite Life Extension Fear Life – Article by Eric Schulke and Wioletta Karkucińska

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The New Renaissance Hat
Eric Schulke and Wioletta Karkucińska
March 23, 2014
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What a repugnant, disdainful, knee-jerk flippancy to flop out of one’s mouth to mock anybody for being afraid of death.

If death doesn’t arouse fear, then what is fear?

We know what fear is. It’s having the sense to understand the level of loss that something imposes upon a person. It’s a no-brainer to understand that life provides value that would diminish to an extensive level if it were to be lost.

Let’s make this even clearer by spelling out what the dictionary tells us about fear.

fear

verb \ˈfir\

: to be afraid of (something or someone)

: to expect or worry about (something bad or unpleasant)

: to be afraid and worried

…

a :  an unpleasant often strong thought caused by anticipation or awareness of danger

b (1) :  an instance of this (2) :  a state marked by this

:  anxious concern :  solicitude

:  reason for alarm :  danger

I don’t have the courage to be robbed or run over; nor should I, or anyone. I have the emotional maturity to understand what my fear is telling me and to equip myself with the courage to join in on the assault on the terrible beast of aging. Watching incredible things unfold in the universe and world, seeing that it is all just the tip of an inconceivably large iceberg, and then seeing that it will be arbitrarily terminated in another of endless, terrible, horrific events for all involved, is alarming. It should concern you that you are standing on the deck of this great star-ship called Earth, and that you might fall off. You should be able to be aware of, and anticipate danger that is ahead. Your stake in the universe is at stake. Your DNA crawled out of your mother’s womb, drove a spike into the universe, asserting a claim in this realm, and death comes along like a miscreant walking up to a land-claim stake, and rips it out and throws it in the river.

“What are you, afraid of death?” They say.

“Don’t be a coward.”

“Because you’re too cowardly to accept death, the rest of us have to help you with your stupid little excursions?”

It’s as though they are saying, “What are you, afraid of cancer? You sissy, your mother and brother have cancer? So what? Don’t act like a wimp. Cancer is what happens. People live, people get cancer. Don’t accept the ice cream and the music if you’re going to whine about the cancer, it’s part of the package. If I could lift a finger to stop people from dying, then I wouldn’t do it.”

Or, it’s like that jerk that you know urging people to walk into woods where there are predators with humans as prey.

“Come on man, walk forty miles through the jungle there. Don’t worry about the lions, mosquitoes, and rhinos. You’ll get through fine, just goooo.” What terrible advice, and what a terrible kind of advice to condone and not discourage!

They are like the trash-talkers on the rodeo machine, where a round of people sit at a teeter-tottering table in the middle of a bull pen while they play cards and talk smack to each other for not continuing to sit in the bull’s eye of imminent death.

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.

What’s more is, that although being afraid is a sensible, logical part of it, the overriding part of it is that most of the people that I talk to that want to live long into the future, do it first and foremost because of their love for life. Most of the people that I know have been thwamped over the head with passion bugs of various kinds by flipping over galactic rocks like philosophy stones, quantum particles, history books and science boulders.

Fighting death has been for ages treated as a battle destined to be lost. How many times, when faced with a loss of a loved one, have we heard “Well, that’s the way of life”? How can one NOT notice the bitter irony and hypocrisy of that statement? How can death EVER be called an element of life, something to accept? It’s the very OPPOSITE of life, NOT part of it, and it is high time we should start seeing it as such. Let the blinders fall from our eyes, once and for all.

We appreciate our opportunity. We appreciate the rarity of humanity and the mind-blowing mysteries we have the privilege to continue to be submersed in. We understand that culture and tradition do not govern the big picture of what it means to exist here.

What it means to exist here is that we are the rare opportunities to know existence. What kind of extremely rare miracle would spring out of the mud after eons of nothingness and then declare that fleeting, flippant, empty cultural traditions of intellectually straitjacketed ancestors of itself are the best dictates for how it should face the big picture of the rapidly unfolding, multifaceted, and to-be-unfettered dreams-come-true (multi?)universe? Would you say that your grandmother’s old typewriter manual is the best guide for figuring out how to fix and program your computer?

What kind of jaw-dropping, paradigm-quaking miracle would spring out of the mud, find science and technology, industry and physics, communications superhighways and knowledge warehouses at the ends of high-speed trails, and all the rest – in many cases at its disposal or within reach of it – and then decide that the best thing for this miracle of the universe to do would be to return to the mud? I can’t tell you how disappointing it is to realize that many of our fellow human beings still think that. It’s also hard to understand exactly how they could think that in a world that emphasizes the value in good, positive critical thinking. They know better than that.

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.

Some people will smugly respond with the assertion that quality is obviously better than quantity. They say that acquiring more happiness now in exchange for taking away their chance to live for continued decades and centuries, is not irresponsible and wrong.

To them we say, our ancestors toiled and struggled through untold and long-lasting hardships to deliver their progeny, you, here to where you are so you can have the opportunities and the ever-brighter futures the generations of your ancestors hoped for, worked for, and achieved. You and your opportunities are their achievement, and I urge you to keep in mind thoughts of not wanting to let them down. You don’t live it up now and then throw away the chance your ancestors gave you. Your job is to survive first, and build empires later. You accept the tough times so that you may continue to earn opportunities to work to build more and more goodness into your life – be that through the completion of more dreams, the building up of more enterprises, the satiation of more curiosity, the fulfillment of more adventure, etc. The tough times help you to savor the good times more. When the ship is on choppy seas and might go down, you hold on tight and work twice as hard. Our ancestors didn’t raise us to throw in the towel. As far as I have ever seen, modern-day Homo sapiens did not evolve with a gene for quitting.

You are set for all the challenges that fighting for life brings. 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.

We once thought the Earth was flat or that all planets revolved around Earth. Many people who have threatened to disrupt tradition and the ways things have been at given times in the world’s history, have faced persecution and shunning for their discoveries. The life of helping move the world forward was hard because the work didn’t often ride forward in a parade of activism and public cheer and action. It would ride forward one hard-fought campaign at a time, one shovel-full at a time, at the hands of small groups of dedicated people working hard to ring the bell of freedom at each new level as humanity continued to expand out into the big picture of the universe and existence. They kept their minds fine-tuned and well-oiled with awareness and focus on what it means to be alive, gathered information, moved humanity forward in various ways, and proved the huge number of skeptics wrong. Life must have felt like hell for them, but they held on and won.

They chose to be courageous in their LIVES. Are you ready to open your mind and face some difficulties in the struggle for life? Would you rather fall asleep and miss out on miracles or stay wide awake and live them?

Eric Schulke was a director at LongeCity during 2009-2013. He has also been an activist with the Movement for Indefinite Life Extension and other causes for over 13 years.

Wioletta Karkucińska is an author and longevity activist in Warsaw, Poland.

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

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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

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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.

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

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

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

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

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

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

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

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

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

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

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

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

More Recent Coverage of SENS Research – Article by Reason

More Recent Coverage of SENS Research – Article by Reason

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

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

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

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

Aubrey de Grey: Out to Defy Death

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

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

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

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

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

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

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

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

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

Who Really Cares – Article by Bradley Doucet

Who Really Cares – Article by Bradley Doucet

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The New Renaissance Hat
Bradley Doucet
January 31, 2014
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I have a pretty positive view of human nature, for a number of reasons. Partly, I’m consciously correcting for the negative bias of “if it bleeds, it leads” journalism. I also reject the idea that being self-interested is necessarily anti-social. Pursuing your own happiness, rightly understood, is a good thing. In fact, I would argue that those who care little for loftier goals like the good of society often do more good than do-gooders, as long as they pursue their self-interest rationally.
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But caring about others is also a good thing, of course. And nobody cares more than those activists, pundits, political leaders, and enthusiastic voters who are involved in fighting to bring about a better society, right? Well, not according to philosopher Michael Huemer. In a very readable and thought-provoking paper entitled “In Praise of Passivity,” Huemer suggests that most people who see themselves as motivated by some high political ideal are instead motivated “by a desire to perceive themselves as working for the noble ideal.”How can you tell who really cares?
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Huemer writes, “If people are seeking high ideals such as justice or the good of society, then they will work hard at figuring out what in fact promotes those ideals and will seek out information to correct any errors in their assumptions about what promotes their ideals, since mistaken beliefs on this score could lead to all of their efforts being wasted.”
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This requires, among other things, reading up on more than one side of a controversial issue. Huemer doesn’t think most people with strong political opinions do these kinds of things. Rather, according to his observations, “most people who expend a great deal of effort promoting political causes expend very little effort attempting to make sure their beliefs are correct. They tend to hold very strong beliefs that they are very reluctant to reconsider.”This tendency certainly counts against my positive view of human nature.
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Given how difficult it is to acquire real knowledge in the social sciences—something Huemer explores in his paper—people who merely want to perceive themselves as working for high political ideals are very likely to do more harm than good. But all is not lost. For one thing, I ascribe no ill will to people who want to feel good about themselves. And fortunately, there are workarounds for our all-too-human cognitive biases. Huemer has several recommendations for how to do some real good (and avoid doing real harm) in the world, recommendations that will surely challenge many people’s assumptions — which is itself a good thing.

 

Bradley Doucet is Le Québécois Libre‘s English Editor and the author of the blog Spark This: Musings on Reason, Liberty, and Joy. A writer living in Montreal, he has studied philosophy and economics, and is currently completing a novel on the pursuit of happiness. He also writes for The New Individualist, an Objectivist magazine published by The Atlas Society, and sings.