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Fight Aging! Newsletter
January 30th 2017
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more.
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Contents
The Million Year Life Span The Mechanisms of Extended Longevity through Increased p53 Activity A Demonstration of Chimeric Tissue Farming: Mouse Pancreatic Tissue Grown in Rats Tackling Cellular Senescence as a Treatment for Aging Keeping a Careful Eye on When You Cease to be You Latest Headlines from Fight Aging! Investigating the Early Stages of Inflammation in Arthritis Are We Terrible at Advocacy, or is it Actually Hard to Persuade People of the Merits of Living Longer in Good Health? A Less Effective Compensatory Response to Mitochondrial DNA Deletions Observed in Parkinson's Disease Patients Why Work to Dismantle Arguments Made Against Increased Healthy Longevity? The Methuselah Foundation's Bioprinting Program Bioprinting Human Skin Cuts the Time Needed from Weeks to Minutes An Example of Transplanted Neurons Integrating into the Brain News of Another Possible Tau Clearance Therapy A Profile of Researchers Working on Heart Decellularization More Evidence for Exosomes to be Important in the Outcome of Stem Cell Therapies The Million Year Life Span
https://www.fightaging.org/archives/2017/01/the-million-year-life-span/
[This is a lightly edited reprint of an article originally published at h+ Magazine, descending from an older Fight Aging! post, and returned again now in order to preserve it for posterity.]
I'm not going to try to convince you that the foreseeable future is a wondrous place: either you accept the implications of the present rate of technological progress towards everything allowed by the laws of physics, in which case you've probably thought this all through at some point, or you don't. Life, space travel, artificial intelligence, the building blocks of matter: we'll have made large inroads into bending these all to our will within another half century. Many of us will live to see it even without the benefits of medical technologies yet to come: growing up without the internet in a 1960s or 1970s urban area will be the new 1900s farmboy youth come 2040. Just like the oldest old today, we will be immigrants from a strange and primitive near-past erased by progress, time travelers in our own lifetimes.
A century is an exceptional life for a human, but far greater spans of years will be made possible by the technologies of the 21st century. I'll plant a flag way out there on the field and claim a million years: a life of a length hard to envisage. I am an advocate for engineered human longevity, and I started on the path that led to Fight Aging! and related projects from the position that (a) immortality would be an unalloyed good if achieved, and (b) our understanding of cosmology does not yet rule out a damn good attempt at actual immortality - the "no death, ever" dictionary definition - or at least a life span of millions of years on the way to that end goal. If a million years is not long enough to figure out the aspects of the problem that cannot be answered today, I'm not sure what would be.
Despite being out there, the million year life span is not an unsupported pipe dream. Living for a million years is a goal that can be envisaged in some detail today: the steps from here to there laid out, the necessary research and development plans outlined, and the whole considered within the framework of what is permissible under the laws of physics, and what the research community believes can be achieved within the next 20, 50, or 100 years.
Biotechnology is the first necessary step on this road of a million years: the biotechnology revolution, still in its early years, is a gateway to the future insofar as it will enable us to extend our healthy life spans by repairing the evolved world of nanoscale machinery within our cells and other vital biological systems. The future is only golden for you and I personally if we live to see it, and for many of us that will require rejuvenation biotechnologies like those worked on by the SENS Research Foundation. This golden future is one in which our biochemistry does our bidding, aging can be repaired, and molecular manufacturing is in full swing. It will be an age of bioartificial bodies, minds transferred to new and more robust mechanisms, artificial general intelligences, an end to most scarcities, and indeed, anything you might imagine that the laws of physics permit and enough time has passed to develop.
A philosophy of first things first is a good way to temper visions of the far future - and explains why I spend my time talking about rejuvenation biotechnologies, cryonics, and even basic common sense health practices that might stop you cutting a mere decade from your life expectancy. If we don't complete the first rung of the ladder, that being sufficient control over our biochemistry to slow and then repair aging, then all the rest of our thoughts on radical life extension are for nothing. If I'd been born twenty years earlier, I'd have ended up primarily a cryonics advocate and volunteer. As it is, it looks like these first decades of the 21st century are the era in which the first rung on the ladder of simply remaining alive forever - which is to say building the means to continuously repair the biological damage of aging in these bodies of ours - can actually be achieved. If we can live another 50 years, grabbing a year here with good health and a year there through incremental advances in geriatric medicine, and if we can build a large enough research community interested in serious work on rejuvenation along the way, then we may live in restored youth and vigor for centuries longer.
If you project forward into the future based today's accident rates, you'll find that an ageless human sustained by biotechnologies of cellular and biochemical repair has a life expectancy in the range of 1,000 to 5,000 years. Sooner or later that piano is going to fall upon your head hard enough that even advanced medical technology cannot fix your injuries in time. So the million year life span: how could that be achieved? The short and not terribly informative answer is that it will be accomplished by using advancing technology to dramatically reduce your vulnerability to fatal accidents, murder, and other unfortunate events that produce the same outcome. Once you start looking at living for even 100,000 years in much the same shape as you are today, it becomes apparent that almost any activity bears an unavoidable minimum level of risk that will jump up and kill you. Eating, swimming, walking ... breathing. Stretch out the timeframe far enough and the improbable and fatal will eventually occur.
The way past these risks is to change your form: your risk of fatality for any given activity is a function of your human physiology. Once the research and development community has achieved the goal of practical biotechnologies for the repair and reversal of aging, that will give us all a few hundred years of life in comparative statistical safety. Technological progress will continue across that long period of time, and I can't imagine that much of the toolkit needed for the next step in long-term risk reduction will remain beyond the capabilities of the human civilizations of the 2200s. Your own personal preferences for that next step will no doubt vary, but I would get my neurons replaced - slowly, one at a time over time, to ensure continuity of the self - with some form of much more robust, easily maintained nanoscale machinery. That allows for a range of new engineering possibilities: swapping out the body for whatever machinery of transport and support best minimizes risk; moving most of the business of life into a virtual world; physically separating my neurons while still remaining alive, conscious, and active.
It shouldn't be terribly controversial at this point to talk about machines that can do the job of a neuron, store all of the same information as a neuron, and integrate fully with surrounding real neurons. Researchers in recent years have assembled lobster neuron simulators from Radio Shack components, grown proof of principle neuron-circuit interfaces, designed and simulated nanomachine replacements for other cell types, and made great inroads into manipulating the internal machinery of cells. These are toys and clunky barnstorming exercises in comparison to what lies ahead, but my point is that this is an active line of research, worked on by thousands of scientists and developers. Similarly, I would hope that interacting via virtual worlds and splitting up one's machine neurons between various locations follows fairly straightforwardly from having machine neurons in the first place. If your brain is made up of artificial neurons, why not throw in an internet connection, adjunct computer hardware, and encrypted wireless communication protocols?
Physical distribution of the self across many disparate locations is in fact the key point when it comes to considering risk over the long term. Locations have much the same issues with time, probability, and bad events as people do. Meteorites are a risk to consider, as are landslides, earthquakes, war, and volcanoes. The way to reduce your location-based risk dramatically is to spread out. You might imagine a wireless brain, using whatever the most robust communications technology of the time happens to be, scattered in a thousand separate machine bodies or vehicles across a continent, or even the whole planet. That might be good for many millennia of falling pianos of various types. However, once you start digging back into the geological and astrophysical history of the solar system, it becomes clear that spreading out over an entire planet still leaves you at risk on longer timescales. Probably not from impact events: I'll be surprised if humanity and its machine descendants fail to solve that problem within the next few centuries. But there will always be war, nearby supernovae, large solar flares, unusually massive volcanic events, and other unpleasant line items, however. Supernovae are the biggest of the known concerns, given that I expect it to be a long, long time before preventing them is a practical and ongoing business for the civilizations that follow man.
What to do about all of this astrophysical and grand geological risk? Spreading out is an option once again. Increase the size of your vehicles and neuron-machines to shrug off the worst case radiation projections for a nearby supernova. Provide them with the means to move about the solar system, and become a spacefaring entity, spread out over a sizeable selection of orbits. By that point in time, your physical presence resembles a small country of machinery, automation, and layers of delegation: perhaps you are a million heavily shielded self-powered containers and transmission systems distributed beyond Pluto's orbit. There is a trade-off for spreading out so far, however, and that is that you must slow down. The speed of thought is determined by the speed of communication between the neurons and sections of your brain. If your brain is light hours wide, you will live very slowly indeed - but with a life expectancy so long that you come out far ahead in the end.
There are other paths forward with varying degrees of risk. You might decide not to spread out, but rather live very fast by running your machine neuron brain on more capable hardware, for example; if you can pass a hundred years of subjective time in a year of real time then you have reduced your subjective risk for many fatal occurrences a hundred-fold. That would be a pleasant enough life as a part of a community of people all running at the same speed, and there is even room for technological development and research to occur at a fair pace under such a scenario. At present our still young computing technology is very, very far removed from the known theoretical limits on computational efficiency. There is a great deal of headroom for the approach of living more rapidly.
But to return to the immortality question: is immortality impractical? Given existing mortality rates and the uncertainties in the timeline for completing efforts to repair and reverse the damage of aging, it may be unlikely for many of us alive today. If progress is too slow, or we are simply unlucky in matters of health, then we won't get past the first step on the path. In other words, we will die - or at best undergo cryosuspension and its attendant risks - before the advent of sufficiently good rejuvenation biotechnology. As for the bigger picture, it is far too early to say whether immortality, the "no death, ever" version, is actually impossible. That requires further research into cosmology - so you might give it a million years or so and ask me again. Regardless, the slope of technology and possibility is curving up ahead of us to great heights, and it'll be a wild ride either way. Missing out on any of it would be a real downer, so why not spend more of your time and resources helping to get the first step accomplished? We should all support the development of rejuvenation biotechnology, as it is the gateway to a life that may ultimately prove to have few limits.
The Mechanisms of Extended Longevity through Increased p53 Activity
https://www.fightaging.org/archives/2017/01/the-mechanisms-of-extended-longevity-through-increased-p53-activity/
The activity undertaken by many important genes is quite subtle and conditional. Simply raising or lowering the amount of protein produced by that gene is rarely as effective as hoped in initial studies, and can be entirely counterproductive. The important activities of any specific protein might be very tissue-specific, and thus thwarted by being altered globally, or they might depend on other proteins and circumstances. The tumor suppressor p53 is a good example of the type; more p53 activity at the right times and in response to the right signals can both extend life and reduce cancer risk in mice. On the other hand, generally increased p53 activity shortens life.
The p53 protein is a part of the complex and shifting tradeoffs made between suppression of cellular replication and encouragement of cellular replication. When there is a greater risk of cancer, when cells are damaged or the cellular environment is toxic, more p53 encourages both greater repair and resistance to cellular damage and a more aggressive removal of cells most at risk by forcing them into senescence. In the normal course of regeneration and tissue maintenance, however, too much p53 suppresses the efforts of the cells that should be replicating, speeding the onset of frailty and organ failure, and over time the presence of larger numbers of senescent cells also leads to an acceleration of the aging process. Senescent cells cause a great deal of harm when they are not efficiently destroyed, either by the immune system or through programmed cell death.
It has been a decade since researchers first demonstrated a way to selectively enhance p53 activity only when needed, producing extension of life in mice. Since then, I think most of the groups involved have been quite distracted by work on telomerase gene therapies, which started in earnest at around the same time and among many of the same researchers, but which has since consumed ever more of the available time and interest. You might recall a merger of these two lines of research in which mice with enhanced telomerase and enhanced p53 activity were found to balance out with a longer life span. Since then the telomerase research has forged ahead, as I'm sure you've all noticed, but I can't say that work on selective increase of p53 activity as a method of modestly slowing aging has advanced all that much at all. The papers today are covering essentially the same ground as was covered a decade ago, and still with little impetus towards building some form of therapy from this:
Increased Arf/p53 activity in stem cells, aging and cancer
| Cancer is the consequence of an aberrant gain of cellular fitness linked to the accumulation of stress and cellular damage of acute intensity. This damage occasionally provides aberrant advantages to certain cells, which can eventually lead to cancer development. The Ink4/Arf locus and p53 are regarded as the most relevant tumor suppressors based on their ubiquitous and frequent inactivation in human cancer. The Ink4/Arf locus encodes three tumor suppressor genes p15Ink4b Laden... Laden... |
