In the near future it will be possible to build artificial bodies, and some decades after that it will become possible to gradually replace the biology of our brains with more durable and capable nanomachinery. A diverse industry of brain-computer interfaces and artificial intelligences will arise and come to maturity along the way. Will we in fact largely become a species of intelligent machines within the next few centuries? By this I mean designed machines, as opposed to the evolved machines we presently are: entities that are human, but very distant from our present forms, functions, and limitations. When you design the machinery, rather than just working with what you have been given, an enormous range of possibilities open up. For one thing, even very complex machines can be designed to be far more robust and easily maintained than our biology, allowing a person-turned-machine-intelligence the option of an extremely long life expectancy.

Will there be a population-scale rush away from biology towards the new and better options for bodies and brains as soon as they become a practical concern? Some people think so, and I believe it is an inevitable transition given the far greater capabilities that could be provided by being more than merely biological. Perhaps not a rush, but a transition over time, leaving behind a disparate collection of Amish-like groups and poor communities that coexist and trade with the transitioned human societies. On the large scale people follow incentives: they buy the new tools that improve life, boost economic output, and add new options at an affordable price. Those groups with the greatest economic output grow to become the cultural mainstream over time. There’s no reason to think that any of this will change, no matter whether society is running on silicon or neurons. Here is an interesting thought, though:

Aubrey de Grey on Ending Aging and the Human Future

I spoke with Aubrey briefly on the topic of the future of humanity, and the potential scenarios (often discussed in the world of transhumanism and futurism) that might involve moving our human conscious into other substrates, giving us long-lasting silicon bodies and potentially moving our minds into computers that are more durable and reliable that our current biological grey matter.

It is Aubrey’s belief that the desire to leave our biological substrate will diminish as the “down-sides” of remaining purely biological go down. In other words, when we can more-or-less live forever in our present bodies, Aubrey believes that we will likely not wish to remove ourselves from them. The negative aspects of “being made of meat” – as he aptly put it – would be mitigated by an absence of disease and an absence of the recurring damage which is the origin of aging itself.

Another way of looking at the incentives of moving from biology to machinery is that it is not just a matter of chasing something better, but also a matter of leaving something undesirable. Discomfort is a great motivator, and evading the terrible suffering and death caused by aging is important to many of those who look with hope to a transhumanist future. Given an industry of rejuvenation medicine and complete control over aging, disease, and pain, however, being a standard issue biological human begins to look like an indefinitely comfortable existence – barring rare fatal accidents, of course, but who goes through life thinking that will happen to them?

So the argument here is that medicine, and specifically the defeat of degenerative aging, will alter the incentive landscape in a way that leads more people to choose to remain biological, even when it is possible to become a machine intelligence with greater capabilities and durability. My estimate of the timelines is that rejuvenation will be a going concern a long way prior to the point at which slow, safe replacement of the brain’s neurons with nanomachinery is possible. It’s possible that the increased comfort provided by the removal of age-related suffering and death will slow down progress towards ways to move biology to machinery.

But we shall see. It is interesting to think about these things, but important not to lose sight of the fact that researchers still need to build the means to reverse degenerative aging. There are detailed plans to show what needs to be done in order to rejuvenate the old, there are plenty of researchers ready to jump in and perform the work if given funding, but resources and public interest are – as ever – lacking. The future only stays fascinating if you remain alive to see it, so consider helping to speed progress towards the means of human life extension.

Source:
http://www.fightaging.org/archives/2013/06/the-incentives-associated-with-becoming-a-machine-entity.php

Source:
http://www.longevitymedicine.tv/the-incentives-associated-with-becoming-a-machine-entity/

Recommendation and review posted by G. Smith

It is good that scientists are now more willing than in past years to talk about human longevity and the prospects for reversing aging through medical science. That change in attitudes is a necessary part of creating an environment in which rejuvenation research programs like SENS can thrive.

This particular group of researchers holds a different view as to which of the known changes in old cells and tissues are fundamental and thus cause aging: in the SENS outline telomere shortening is a secondary effect and nuclear DNA damage is only a cause of cancer rather than aging, but this paper puts them front and center as primary causes of aging. These researchers are also as yet unwilling to explicitly talk about rejuvenation rather than simply slowing aging, but a rising tide floats all boats.

All in all I’m very pleased to see scientists independently following the SENS model by producing a work that combines (a) specific descriptions of the changes proposed to cause aging and (b) specific proposals on how to use this information to build therapies that will address aging. The paper is open access for the moment at least, so you might take a look:

For some species, living twice as long in good health depends on no more than a few genes. When this fact was revealed by studies on worms three decades ago, it ushered in a golden age of ageing studies that has delivered numerous results, but also sown some confusion. [Researchers are now] publishing an exhaustive review of the subject that aims to set things straight and “serve as a framework for future studies.” All the molecular indicators of ageing in mammals – the nine signatures that mark the advance of time – are set out in its pages. And the authors also indicate which can be acted upon in order to prolong life, while debunking a few myths like the belief that antioxidants can delay aging.

The authors are Spanish scientists Maria Blasco (Spanish National Cancer Research Centre, CNIO), Carlos López-Otín (University of Oviedo), and Manuel Serrano (CNIO), along with Linda Partridge (Max Planck Institute for Biology of Ageing) and Guido Kroemer (Paris Descartes University). Their inspiration came from a classic 2000 paper, The Hallmarks of Cancer, [which] marked a watershed in cancer research.

[This] removes the “frivolity” with which aging research is often approached: “It’s not about not having wrinkles or living to be a hundred at any cost, but about prolonging disease-free life.” [The] scientists are explicit about their final goal, which is “to identify pharmaceutical targets to improve human health during aging.”

Another milestone of the paper is that it not only defines the nine molecular hallmarks of aging but orders them into primary hallmarks – the triggers; those that make up the organism’s response to these triggers; and the functional defects resulting. This hierarchy is important, because different effects can be achieved by acting on one or other of these processes. By acting on just one mechanism, if it numbers among the primaries, we can delay the aging of many organs and tissues.

There are four primary causes of aging: genomic instability; the shortening of telomeres; epigenetic alterations; and loss of proteostasis.

Genomic instability refers to the defects the genes accumulate over time, due to intrinsic or extrinsic causes. The shortening of telomeres – the protective caps over the ends of chromosomes – is one such defect, but so important a one that it stands as a hallmark in its own right. Epigenetic alterations are the result of lived experience – our exposure to the environment.

Loss of proteostasis has to do with the non-elimination of defective proteins, whose accumulation promotes age-related diseases. With Alzheimer’s, for instance, neurons die because plaques form of a protein that should have been eliminated.

The organism responds to these triggers with mechanisms that try to correct the damage, but which can themselves turn deleterious if they become exacerbated or chronic. This is the case of cellular senescence: the cell is induced to stop dividing, and thus prevent cancer, when too many defects are built up, but if the effect is overdone, the tissues – and the body – age.

One therapeutic strategy tested successfully in mice is to stop the telomeres from shortening. “The process can be halted and even reversed in mice,” remarks Blasco, an expert in the area, who is convinced that, by and large, “we still have ample room for manoeuver to combat aging and enjoy more years of both life and health.”

For López-Otín, “We have diverse opportunities to extend longevity in the not too distant future. Treatments aimed at reducing or correcting the genomic damage that occurs with time are still a distant prospect, but those focusing on metabolic regulation systems may be much more achievable. We don’t aspire to immortality, just to the possibility of making life a little better for us all.”

Link: http://www.eurekalert.org/pub_releases/2013-06/cndi-srw060313.php

Source:
http://www.fightaging.org/archives/2013/06/a-good-scientific-polemic-on-aging.php

Source:
http://www.longevitymedicine.tv/a-good-scientific-polemic-on-aging/

Recommendation and review posted by G. Smith

It was once thought that the brain did not generate new neurons in adult life, but the evidence for ongoing neurogenesis was found a few decades ago. Levels of neurogenesis in humans have been hard to pin down, but knowing the degree to which it happens naturally has some relevance to attempts to induce a higher rate of neuron creation with the aim of reversing age-related loss of cognitive function. Here researchers find a way to quantify the level of cell turnover in at least one part of the brain:

The birth of new neurons in the adult brain sharpens memory in rodents, but whether the same holds true for humans has long been debated. A [study] reveals that a significant number of new neurons in the hippocampus – a brain region crucial for memory and learning – are generated in adult humans. The researchers used a unique strategy based on the amount of carbon-14 found in humans as a result of above-ground nuclear testing more than half a century ago. The findings suggest that new neurons are born daily in the human hippocampus, offering the tantalizing possibility that they may support cognitive functions in adulthood.

Due to technical limitations, until now it was not possible to quantify the amount of neurogenesis in humans. To overcome this hurdle, [researchers] developed an innovative method for dating the birth of neurons. This strategy takes advantage of the elevated atmospheric levels of carbon-14, a nonradioactive form of carbon, caused by above-ground nuclear bomb testing more than 50 years ago. Since the 1963 nuclear test ban treaty, atmospheric levels of “heavy” carbon-14 have declined at a known rate. When we eat plants or animal products, we absorb both normal and heavy carbon at the atmospheric ratios present at that time, and the exact atmospheric concentration at any point in time is stamped into DNA every time a new neuron is born. Thus, neurons can be “carbon dated” in a similar way to that used by archaeologists.

By measuring the carbon-14 concentration in DNA from hippocampal neurons of deceased humans, the researchers found that more than one-third of these cells are regularly renewed throughout life. About 1,400 new neurons are added each day during adulthood, and this rate declines only modestly with age.

Link: http://www.eurekalert.org/pub_releases/2013-06/cp-ntf053113.php

Source:
http://www.fightaging.org/archives/2013/06/quantifying-neurogenesis-in-adult-humans.php

Source:
http://www.longevitymedicine.tv/quantifying-neurogenesis-in-adult-humans/

Recommendation and review posted by G. Smith

Of the billions presently alive, some fraction will go on to live for thousands of years. The age of rejuvenation therapies is just around the corner, and new approaches to medicine will enable the old to be made young again. This will happen within a few decades, perhaps soon enough for those in middle age today in wealthier regions, perhaps not. Whatever the timeline turns out to be – and we have the opportunity to accelerate it – the fundamental forms of cellular and molecular damage that cause aging will become just another set of chronic medical conditions that are kept under control with regular treatments: periodically repaired, so as to maintain youth and indefinitely postpone age related disease.

In this future people will still die, however. The current mortality rate due to fatal accidents, if maintained, would give an ageless, disease-free person a life expectancy of a few thousand years. If you want to live longer than that, then you require either (a) the means of greatly reducing the occurrence and severity of accidents, or (b) to ability to change yourself to be less vulnerable. Those people alive today who are still alive ten thousand years from now, and some will be, will most likely have altered themselves dramatically, abandoning flesh and the human form in favor of far more robust machinery.

It should not be terribly controversial to suggest that a hundred years from now replacing your body with an artificial chassis will be a very feasible, cost-effective option. The manufacturing and design technologies of that era will involve mature artificial intelligence and precise atomic construction. An artificial body should be a simple undertaking by that point, and there’s more than enough time to wait for that technology if you survive today’s first hurdle of living long enough to benefit from the first wave of rejuvenation biotechnologies.

When it comes to transforming yourself into an entity likely to survive for longer than recorded human history to date, the body is a trivial matter, however, hardly worth putting much thought into at this point. Almost any easily replaceable, mobile, and very robust machinery will do. The more interesting questions relate to the brain and the self: how can you switch out the intricate biology of the brain for more durable machines without killing yourself in the process? All that is you is encoded as data in the fine structure of brain tissue. Making a copy of your mind to run as software seems like a feasible undertaking, something that can be envisaged even today: it’s possible to speculate in a useful fashion as to how that might be accomplished within the next few decades. But a copy of you is its own entity, not you, and there are many other questions and doubts relating to the continuity of the self associated with an intelligence running as software.

The best approach to replacing the brain while retaining your self is a slow process of replacing each neuron with machinery that serves exactly the same purpose and integrates with the rest of the brain in exactly the same way as the neuron did. The brain creates and loses neurons on an ongoing basis already – though a plausible replacement methodology would run many times faster than that process, and would replace neurons that are normally never replaced. Some of those cells last a lifetime.

This gradual neural replacement is a fine thing to talk about in abstract, but how would it even work in practice? How would a neuron machine be constructed? How do you assure continuity of the self when doing this for real? Some people have put a fair amount of thought into this topic, even though it is a far future prospect and we still have to sort out the first step of not aging to death in the bodies and brains we have now. Over at the Rational Argumentator you’ll find an eleven part series on the important parts of the path to replacing the brain with machinery. There’s quite a lot of reading material there, and I make no warranty as to the quality and rigor of the work, but I think you’ll find it interesting.

1. The Moral Imperative and Technical Feasibility of Defeating Death
2. Immortality: Material or Ethereal? Nanotech Does Both!
3. Concepts for Functional Replication of Biological Neurons
4. Gradual Neuron Replacement for the Preservation of Subjective-Continuity
5. Wireless Synapses, Artificial Plasticity, and Neuromodulation
6. Mind as Interference with Itself: A New Approach to Immediate Subjective-Continuity
7. Neuronal ‘Scanning’ and NRU Integration
8. Squishy Machines: Bio-Cybernetic Neuron Hybrids
9. Choosing the Right Scale for Brain Emulation
10. Maintaining the Operational Continuity of Replicated Neurons
11. Immortality: Bio or Techno?

If we seek to replace biological neurons with artificial equivalents, once we have a simulation of a given neuron in a computer outside the body, how is that simulated neuron to communicate with the biological neurons still inside that biological body, and vice versa? My solution was the use of initially MEMS (micro-electro-mechanical systems) but later NEMS (nano-electro-mechanical-systems) to detect biophysical properties via sensors and translate them into computational inputs, and likewise to translate computational output into biophysical properties via electrical actuators and the programmed release of chemical stores (essentially stored quantities of indexed chemicals to be released upon command). While the computational hardware could hypothetically be located outside the body, communicating wirelessly to corresponding in-vivo sensors and actuators, I saw the replacement of neurons with enclosed in-vivo computational hardware in direct operative connection with its corresponding sensors and actuators as preferable.

I didn’t realize until 2010 that this approach – the use of NEMS to computationally model the neurons, to integrate (i.e., construct and place) the artificial neurons and translate to biophysical signals into computational signals and vice versa – was already suggested by Kurzweil and conceptually developed more formally by Robert Freitas, and when I did, I felt that I didn’t really have much to present that hadn’t already been conceived and developed.

However, since then I’ve come to realize some significant distinctions between my approach and Brain-Emulation, and that besides being an interesting story that helps validate the naturality of Immortalism’s premises (that indefinite longevity is a physically realizable state, and thus technologically realizable – and what can be considered the “strong Immortalist” claim: that providing people the choice of indefinite longevity if it were realizable is a moral imperative), I had several novel notions and conceptions which might prove useful to the larger community working and thinking on these topics.

Source:
http://www.fightaging.org/archives/2013/06/considering-the-details-of-replacing-the-brain.php

Source:
http://www.longevitymedicine.tv/considering-the-details-of-replacing-the-brain/

Recommendation and review posted by G. Smith

I believe it’s a grand waste of time to try to optimize your health through presently available methods. It’s very easy to get the 80/20 best expected outcome: exercise regularly, practice calorie restriction with optimal nutrition, and refrain from methods of self-harm such as smoking, jumping off tall buildings, and so on. This is not rocket science.

There is no scientific support for going beyond this to tinker with types of exercise, esoteric supplements, and the like, however. There’s no way to link your future life expectancy with your activities, and there is no good weight of evidence to suggest that any of the thousands of available options are better or worse for life expectancy than the 80/20 approach. There is always someone out there pushing a new fad, but that doesn’t make it right, useful, or legitimate. Maybe you’ll improve your life span by a few percentage points, and maybe you won’t. There is no way to tell, and the time and money easily wasted on that endeavor is better put to other uses that are far more likely to extend your healthy life span – such as supporting the research needed to produce rejuvenation biotechnology.

That all said, it’s possible to go too far in the direction of doing little but the basics for your health – if you are thinking of letting it all go and doing nothing for your health, that will have consequences. This view is illustrated in the post quoted below, wherein the author rejects calorie restriction on the basis that the present consensus view is that it won’t extend healthy life in humans by all that much. This ignores the amazing health benefits demonstrated in human studies to date – calorie restriction may or may not extend human life by more than a few years, but it certainly greatly improves measures of health and lowers risk of age-related disease. It seems silly to reject something shown to produce larger benefits for basically healthy people than can be gained by any presently available medical technology.

I want to live longer and help others do the same. I assumed the most effective way to do that is by understanding the science of aging and then engineering solutions to extend human lifespan. That is why I became a biomedical researcher and over the past several years I have pursued this goal almost single-mindedly.

When a 2004 study showed that reducing the calorie intake in mice extended their life by 42%, I enthusiastically embraced the results and even put myself on a calorie restricted diet. But, subsequently, a 2012 study showed that long-term calorie restriction may not have the promised benefits. On the contrary, fewer calories without the required nutrients might actually cause harm.

Calorie restriction is not the first such “promising” route that eventually did not live up to the promise, and it will not be the last. Antioxidants showed promise in holding back diseases caused by aging, but now we know that antioxidant supplements are more likely to shorten your life.

Earlier in May, researchers showed that reducing a protein called NF-kB in mouse brains modestly improved their lifespan. I am not holding out for this result either. Before too long, I’m sure there will be reports of severe side effects of manipulating levels of NF-kB.

Looking at the data I have come to the conclusion that “doing nothing” may be the best option in most cases. This may not be as pessimistic as it sounds and it is definitely not to say that research in fighting aging must not be carried out. When I say “do nothing”, I am assuming that you do not smoke or drink too much alcohol, and have access to medical care in case of injury. Such measures are bound to increase your lifespan.

But currently, not intervening in the aging process is more likely to help you live longer than trying any of the methods I’ve mentioned, not by a few months but by many years. Trying any of those interventions may actually cause harm, and will do so for the foreseeable future.

I agree with the basic thesis here, which is to be a late adopter and refrain from chasing the latest fads and data – this is an aspect of what I am arguing with my view on the futility of trying to optimize health past the 80/20 basics. But again, you can take it too far and throw the baby out with the bath water. Calorie restriction with optimal nutrition has an enormous weight of evidence gathered over decades backing its benefits and safety, and the same goes for regular exercise.

Link: http://lifeboat.com/blog/2013/05/do-nothing-to-live-long

Source:
http://www.fightaging.org/archives/2013/06/overreacting-in-the-direction-of-doing-nothing.php

Source:
http://www.longevitymedicine.tv/overreacting-in-the-direction-of-doing-nothing/

Recommendation and review posted by G. Smith

Shrikant MaliIndian Journal of Human Genetics 2013 19(1):3-8The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities ar…Source:
http://www.medworm.com/index.php?rid=7326951&cid=c_449_50_f&fid=33830&url=http%3A%2F%2Fwww.ijhg.com%2Ftext.asp%3F2013%2F19%2F1%2F3%2F112870

Source:
http://www.longevitymedicine.tv/delivery-systems-for-gene-therapy/

Recommendation and review posted by G. Smith