World Health Organization

Aschwin de Wolf continues to republish important writing from the early days of the modern healthy life extension community at Depressed Metabolism. Those were the years of the late 1960s, in which the seeds were laid for the cryonics community on the one hand and pro-longevity supplement and "anti-aging" groups on the other. There's really a deep divide between the two factions in terms of fundamental philosophy: on the one hand aiming a few more years (or decades, as they overoptimistically thought at the time) of healthy life via applied pharmacology, on the other the engineer's path to defeating death completely. Quite different worlds of ambition - and as it turned out, rationality. The cryonicists, with visions of immortality in their sights, were far more correct about the bounds of the possible, given scientific knowledge at the time.

Once vitrified and stored at low temperature, a cryopreserved individual has time and the astounding curve of scientific progress on his side. The laws of physics and our present understanding of brain biochemistry place no obstacles in the path of restoring cryopreserved people - it's a matter of developing the necessary medical technology, and remaining well-stored until that time comes to pass.

Now "immortality" is a much abused term, cast widely and with many colloquial meanings. Linguistic drift has come to put it somewhere between "long-lived" and "ageless but vulnerable to accident" in all but more precisely spoken communities. But it was much used by the early cryonicists in a way closer to the dictionary definition, and that more than anything else I think captures their excitement at having envisioned the scientific doorway out of the trap - a tool that could provide a possible way around death. For example, the early cryonics book "Immortality: Physically, Scientifically, Now" by Ev Cooper, subtitled "A reasonable guarantee of bodily preservation, a general discussion, and research targets":

Now in the last half of the 20th century, to take seriously that physical immortality, here on earth, is scientifically possible is almost as much as dream can encompass, certainly more than sobriety can allow. This is perhaps a necessity, for it is only more absurd to chase after every South Sea bubble. And, ever since prehistoric man first imagined the possibility of life forever, the countless rolling centuries have not given him one shred of material verifiable evidence. Now, however, when some of the scientific possibilities appear on the horizon, someone has to form the question, consider a reversal of the skepticism engendered by centuries of disappointment and prepare the way for the reality of the incredible.

Why was cryonics envisaged as the step directly to immortality? Because, should the plausible outline of the process work, it is a gate to the future of far more capable technology. A future after the biotech revolution, in which our biochemistry does our bidding, aging can be repaired, and molecular manufacturing is in full swing. An age of bioartificial bodies, minds transferred to new and more robust mechanisms, strong artificial intelligences, and indeed, anything you might imagine that the laws of physics permit and enough time has passed to develop.

I'm not going to try to convince you that the future will be a golden, wondrous place: either you accept the implications of the present rate of progress towards what the laws of physics make possible, in which case you've probably thought this all through at some point, or you don't. Life, space travel, AI, the building blocks of matter: we'll have made large inroads into bending it all to our will within another half century. Many of us will live to see it even without the benefits of medical technology to come: growing up in a 1970s urban area will be the new 1900s farmboy youth come 2040; a strange and primitive near-past erased by progress, for all that so many people still alive actually lived it, time travellers in their own lifetimes.

In any case, I think it's interesting to ponder why cryonics is no longer seen quite so stridently as the gate to immortality, despite the fact that cryonics technology has advanced steadily since the 1960s, as has our understanding of our brain's biochemistry. Could it be because that the horizon for successful restoration has pulled in - perhaps as early as the 2040s? Cryonics advocates no longer expect to be restored to a time massively different to our own, because the journey will likely be one of decades rather than centuries.

The vision of immortality can still be conjured just as stridently, should we so wish, but it's somewhat fashionable at the moment to distance oneself from talking about immortality. There are practical aspects too. Now that we have serious, scientific work taking place aimed at the repair of aging, and fundraising for faster progress is an earnest endeavor, one can't afford to be throwing around words that can be easily misconstrued. The path to moderation of the vision is hard to avoid once money starts flowing in.

I started on the path that led to the Longevity Meme and Fight Aging! from the position that immortality was a good thing, and knowing that the laws of physics did not disallow 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 that's not long enough to figure out the aspects of the problem that cannot be answered today, I'm not sure what would be. If I'd been born two decades earlier, I'd have been a cryonics advocate and volunteer. As it is, it looks like these first decades of the 21st century are the era in which step one (of thousands, no doubt) of simply remaining alive forever - continuously repairing aging in these bodies of ours - can be achieved.

A philosophy of first things first is a good way to temper visions of steps two through however many thousand, and explains why I spend my time talking about the Strategies for Engineered Negligible Senescence and the biotechnology revolution. If we don't complete the first step, sufficient control over our biochemistry to repair aging, then it's all for nothing.

So, the million year life span: how could that be achieved? The short, and not terribly informative answer is that you get it done by using advancing technology to dramatically reduce your vulnerability to fatal accidents, murder, and the like. If you project out the accident rates for life today, you'll see that an ageless human, sustained by forseeable biotechnologies of cellular and biochemical repair, has a life expectancy in the 1000 to 5000 year range. Sooner or later that piano is going to fall on you hard enough that even advanced medical technology can't fix you up.

Once you start looking at living for 100,000 years in much the same shape as you are today, it becomes apparent that almost any activity bears a level of risk that'll jump up and kill you. Eating, swimming, reading ... breathing. Stretch out the time for long enough and the improbable and fatal will happen to you.

The answer is to change the shape you are. Getting past step one, the repair of aging, gives you a few hundred years of comparative statistical safety. I can't imagine that much of the technology needed for step two will remain beyond the human civilization of the 2200s. Your step two 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 nanomachinery. That allows these sorts of engineering possibilities:

• Swapping out the body for whatever machinery of transport and support best minimizes risk
• Moving most of the business of life into simulation
• Physically separating my neurons while still remaining alive, conscious and active

It's that last point that's key, as physical locations have the same sort of issues with time, probability and bad events as people do. Meteorites happen, as do landslides, earthquakes and volcanoes. The way to reduce your risk function dramatically is to spread out. You can imagine a wireless brain (using whatever the most robust communications technology of the time happens to be be) scattered in a thousand separate locations across a continent, or the whole planet.

That should be good for 10,000 years of falling pianos of various types. However, once you start digging back into the geological and astrophysical history of the solar system, it's clear that spreading out over an entire planet still leaves you at risk on longer timescales. Probably not from impacts: I'll be surprised if we can't solve that problem within few centuries from now. There's always war, nearby supernovae, massive unexpected solar flares, and other unpleasant items, however. The supernovae are the biggest of the known concerns, given that I expect it'll be a long, long time before preventing them is a practical and ongoing business for the civilizations that follow man.

Spreading out is an option again: boost up the size of your components and neuromachinery for worst-case-scenario radiation projections, 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 nanomachinery, automation and delegation. The trade-off for spreading out and further greatly reducing your long-term risk of death is that you slow down. The speed of thought is determined by the speed of communication between neurons in components in different orbits. If your brain is light hours wide, you will live very slowly indeed - but for so long, that you come out ahead.

There are other paths forward, of course, with varying degrees of risk and invention. I haven't touched living very fast in simulation by running your brain on faster hardware, for example. The practicality and possibilities as determined by the laws of physics and what we have invented to date have been debated well over the past decades of the transhumanist community; if you head out there online to look, you'll find a wealth of fascinating material.

Is immortality impractical? Given the risk functions and uncertainty in the timeline for completing the repair of aging, it might be unlikely for most of us alive today because we won't get past step one. But it's far too early to say whether immortality, the "no death, ever" version, is actually impossible for all of us. Give it a million years and ask me again. The slope of technology and possibility is curving up ahead of us to great heights, and it'll be a wild ride either way.

Insulin-like growth factor 1, IGF-1, is one of a number of items of great interest for the mainstream of gerontology, those researchers focused on the workings and manipulation of metabolism. It also remains an area of uncertainty at this time, with apparently contradictory results abounding:

Adding more IGF-1 in an unmodified metabolism seems to be good, but modifying metabolism to completely remove it seems to be much better. To add to these results in animals, an improved testing methodology for humans shows that more IGF-1 activity is apparently better in the elderly:

These new findings come as a result of a new form of testing for IGF-bioactivity. Researchers in this study used a new method, a bioassay, to measure the function of IGF-1 in the blood. Compared to commonly used methods to measure IGF-1, the IGF-1 bioassay gives more information about the actual function (bioactivity) of circulating IGF-1 in the body.

What this doesn't tell us is whether IGF-1 activity is a cart or a horse in this correlation - cause, consequence, or a little of both? I suspect that levels of IGF-1 activity are greatly influenced by obesity, metabolic syndrome, diabetes, general aerobic fitness, risk of atherosclerosis, levels of oxidative stress, and other line items of biochemical damage and poor choice that correlate with a lowered life expectancy.

So eating yourself into an early grave and hoping to dig your way out with hormone supplementation is not the way to go, as always. Neither life nor your metabolism works that way.

A stem cell niche is an environment within the body where a specific variety of stem cell is nurtured:

Niches age with the rest of your tissue, and for much the same reasons; an accumulation of a variety of types of cellular and biochemical damage. The machine gathers faults and rust over the years, and gradually moves towards serious failure.

There has been some debate over the past few years as to whether the well-known decline in function of stem cell populations with age occurs because of changes in the stem cells, or because of changes in their niches. It seems that the consensus is presently leaning towards the niche explanation:

It is the stem cell niche that (i) maintains HSC in a quiescent state that reduces DNA damage as well as replicative senescence, (ii) protects from radicals and toxic compounds, (iii) regulates cell intrinsic signal cascades and (iv) modulates gene expression and epigenetic modifications in HSC. Thus, the interplay with the stem cell niche controls HSC function including the aging process of the hematopoiesis.

As accumulating age-related damage causes the cells and processes of the niche to malfunction, the stem cells it supports suffer. One consequence of the dominance of the aging niche is the direction taken in order to develop the next generation of stem cell therapies. Clearly it's not enough to gain far better control over stem cells if the damaged niche then sabotages your efforts.

I believe that this will likely see the large and well-funded regenerative medicine industry start down the path of trying to rejuvenate and repair stem cell niches. I don't know when that will start in earnest, but it will be a tremendous opportunity for those of us interested in the success of more general strategies for biochemical repair throughout the body - a chance to apply large-scale funding and a large research community to specific challenges in repairing the damage of aging.

Incentives matter in all areas of human endeavor. When people gather to develop and deploy new medicines, for example, they are more incentized by the prospect of personal gains - reputation, profit, feeling good by doing good, and so forth - than by the benefits brought to people they have never met. This is simple, hardwired human behavior. Exceptions are few and far between.

That we instinctively work to improve our own lot first is why progress for all happens so much faster in free, open marketplaces under the rule of law. There, everyone can trade to make themselves better off: specialization and comparative advantage means that trade benefits both sides. Trade is not zero-sum; we grow the whole pie by specializing and trading the results of our work. You go off and work to make the medicine I want, and many people like myself give some our our resources to purchase the end result. Both sides benefit, exchanging - what is for them - lesser value to receive greater value.

There is no open marketplace for medical technology in the developed world, however. Instead, we see a very different set of incentives dominating the state of research and development. Regulatory bodies like the FDA have every incentive to stop the release of new medicine: the government employees involved suffer far more from bad press for an approved medical technology than they do from the largely unexamined consequences of heavy regulation. These consequences go far beyond the obvious and announced disapproval of specific medical technologies: the far greater cost lies in all the research, innovation and development that was never undertaken because regulatory burdens ensure there would be no profit for the developer. Personal gain for the regulator is thus to destroy the gains of people they will never meet, the exact opposite of what occurs in an open marketplace.

An article that looks at one small part of the destruction caused by the FDA caught my attention, and particularly these snippets:

It would have been the first new drug for prostate cancer in 20 years

Twenty years! Just stop a moment and think about how far and fast biotechnology and medical science has moved in the past twenty years. Think about what the far less regulated computing industry has acheived in the same timeframe. We live in the early years of the biotechnology revolution, with something amazing and new demonstrated in laboratories every week. Yet the dominant regulatory body for one of the most advanced regions of the world has managed to stop the clock at 1988 for a major disease, the subject of research in a hundred laboratories worldwide.

This sitation exists in every field of medicine, and all participants labor under the crushing burdens imposed by regulators incentivized to stop progress from happening. The same will be true of the future of longevity medicine, unless we do something about it.

The insanity of this all is quite staggering - that people largely accept and defend the need for regulation that achieves this sort of result, that is. I have heard it said that the failure of libertarianism, of the urge to freedom and personal responsibility, is a failure of imagination on the part of those who have been brought up knowing nothing other than government and regulation on a massive scale. The majority cannot make the leap to see an unregulated marketplace for medical development that works in the same way as the unregulated marketplace for computers - enormous choice, low barriers to innovation, efficiency and low cost, competing review organizations, accountable sellers, rapid progress and responsiveness to customers driven by fierce competition, and so forth.

What is, is, and to propose another way is already an uphill battle regardless of merits. That is also hardwired into the human condition. But the present dismal state of affairs must be changed if we are to see the defeat of degenerative aging in our lifetime - nothing short of a revolution is called for, given just how far in the hole we find ourselves. The technologies needed to repair aging will take only a few decades to develop, and indeed some already exist in prototype, but the present regulatory burden placed upon medical technology will ensure we are all dead and buried, that wondrous potential squandered.

Over at the Electric Pulse, you'll find a good introduction to the Strategies for Engineered Negligible Senescence, aimed at those folk completely unfamiliar with longevity science and the work of scientists like Aubrey de Grey:

We will soon be able to deal with the nanoscale devices that make up the human machine and fix the damage that occur to them.

This is a great piece to send to friends and relatives who don't follow scientific progress at the Methuselah Foundation, and don't know about relevant new research out in the wider life science community - indeed, to anyone you know who doesn't spend much time thinking about aging at all. The article is simple and to the point, framing aging as the consequence of known forms of biochemical damage, presenting the best path forward as the development of therapies to repair that damage.

The biggest hurdle to the future of healthy life extension not the science, but rather that most people in the world take aging and its degenerations as writ in stone, an immutable fact of life. Only when many more folk appreciate that aging can be defeated - and defeated within our lifetimes - will we see rapid progress, large-scale funding, and the growth of a large research community to get the job done. That's something we can all help to bring about by talking more often about real science and real prospects for engineered longevity.