We now know pretty much all we need to know about aging in order to develop medicines that can keep people truly youthful in old age, and if only we realized that, we’d be doing that development a whole lot faster. We often discuss the impact that a longer human lifespan might have on future societies, and even published an article devoted entirely to Life Extension and its impacts on civilization if we get it working.
Today though, we’ll be more focused on the science of aging and how we might actually treat it. There’s always a lot of skepticism toward Life Extension, which is a big problem when discussing and researching the topic. Although, it isn’t quite right to call it skepticism, because that’s not quite what it is. Pessimism and cynicism often masquerade as proper skepticism these days but it’s not really that either. Some technologies enjoy more optimism then they probably merit, others less, but for life extension it’s more akin to an attitude of fear to contemplate it. Taken apart, almost no one’s view of aging is grounded in the details of the medical challenges required to develop therapies against aging, but a built-in acceptance that growing old and dying is somehow natural and necessary.
People, sometimes even experts in medicine, simply wave the challenge aside as a problem we can’t tackle, or not for a long time. This makes it a good topic for us here at EduQuarks, since we often deal with problems and challenges of the distant future, but something we’ll see today is that in this case, life extension isn’t something of the far future, or even of the future at all. It’s just an extension into the next frontier of things we’ve been successfully doing for quite some time. We have to understand that the topic tends to invite blanket statements and proclamations about its viability because aging itself is quite a blanket term.
Many of the concepts we associate with old age, are no longer viewed as natural causes of death, even though this is likely a mistake. We’ll be looking at Strategies for Engineered Negligible Senescence of organisms, which is quite a mouthful, so it’s abbreviated to SENS. What it means is researching ways to repair the damage to the cells and functional molecules in our bodies that drives us into disease and debility in old age. We’ll be covering seven main categories of SENS, all suffixed by that term, SENS, and I’ll introduce them in turn as we go.
Cancer is viewed by many as the primary scourge of humanity going forward. Many folks in our current world die from cancers or its associated complications, so let’s get that big one out of the way first. Cancer is addressed under the heading of OncoSENS, which is derived from the same Greek word as “oncology”, a branch of medicine that deals with the prevention, diagnosis, and treatment of cancer. Cells, to be part of complex multicellular organisms, need to replicate in a very controlled way, and that includes dying when they break down. Cell senescence, the deterioration of a cell to the point at which it can no longer successfully divide, is one form of cellular aging. On the other hand, cancer is where a cell begins to divide uncontrollably.
This can happen at any age, but it grows increasingly likely with time and exposure to certain risk factors. This means that if we extend the average human lifespan we’re likely to see an increase in mortality resulting from cancer. So addressing cancer is part of the equation for achieving life extension. Our bodies already do this too, so we just need to help them out. One of the mechanisms we’ve evolved for fighting cancer is Telomere shortening.
Your DNA has non-coding end caps on it called telomeres that get shorter each time a cell divides; this process acts like a fuse or timer against mutation After a cell has divided100 times or so, it is probably too mutated and damaged to make further copies of, so it gets shut down, replicative cell senescence. This end cap can begin longer or shorter, which is usually associated with cell-type. Longer ones divide more times before shutting down, which has both advantages and disadvantages. Our reproductive cells and adult stem cells have an enzyme called Telomerase that builds telomere length back up in them, otherwise every species with this timer would just die off.
Unfortunately, this is a double-edged sword since cell senescence is only a defense against cancer in the short term. And longer lived cells have a higher risk of becoming mutated to ignore signals to senesce, which can actually promote cancer in the long term. Dealing with these mutants will be one of the strategies we discuss later. However, there are two key concepts that need to be addressed before we get into too much more detail here.
First, some folks are skeptical as to whether or not stopping or slowing aging is an ethically and morally right thing to do. Such skepticism is, however, unjustified when we realize that the so-called diseases of old age like cancer are actually byproducts of aging. For example, cancer is part of aging and we treat that, and should too. I don’t want to die from cancer and I don’t know anyone who does, or who doesn’t favor treating it; and most people would feel the same way about the other age-related problems which we’ll be discussing in this article. There will be a lot of consequences to our civilization if we master aging, not all of them good.
We discussed that more in the Life Extension article last year and in other articles too. But that decision has already been made, in the sense that we extend life every time we give a treatment, perform a surgery, or administer therapy. The second key point relates not just to cancer, but to all medicine. Virtually every aspect of medicine is designed to either extend life or improve our comfort. As we age those become harder to manage and generally we deteriorate faster if we’re not managing our health as we go.
Again, we all take as a given that you should actively seek to maintain your health throughout life, with the intention of living longer and enjoying a better quality of life in the process. So even if one argues that fighting aging may be ethically dubious, it would appear to be a choice we already make every day. For all of our general skepticism about prolonging the human lifespan or even extending it indefinitely, we have consistently embraced every technology and practice which has been demonstrated to extend how long we live. Well, almost every practice.
While available data indicates that castration may significantly extend our lifespan, not many gentlemen would be interested in that option. So it’s also good to remember that quality of life is as important as duration of our lives, and the various methods we’re discussing today are intended to extend our vitality too, not just how long we’ll live. For the most part, modern medical practices are not just extending how long people live on average, but how long they are healthy and vigorous too.
This new medicine will be unambiguously good for our vitality, since it will extend our lives precisely because it keeps us young and healthy, thereby forestalling the diseases and debilities of aging. For the most part, twentieth century medicine drastically reduced causes of mortality early in life. This had the effect of significantly increasing the average lifespan. However, since people were living longer, we saw an increase in many, previously uncommon forms of late-life mortality.
As a result, in the past several decades’ medical science began focusing on the treatment and prevention of geriatric illnesses. While this doesn’t raise the average lifespan quite as much as preventing fetal mortality, it leads to generally healthier older people. This ties into a concept we usually call Longevity Takeoff or Escape Velocity. The notion that the lifespan keeps increasing a little bit here and there, until eventually you have people being born who will not die of old age because we’re improving things throughout their life, extending that life, until you get a generation who never quite dies and lives long enough to enjoy something regenerative. A lot of us feel we may have already hit that point, and that there are people alive today who will live to see an end to aging, or at least vastly extended lifespans of centuries or millennia.
So I mentioned various strategies for studying and fighting biological aging, again SENS, and we already covered one, cancer, or OncoSENS. But what are the others? The next we’ll hit, amusingly, is addressing issues with symbiotic bacteria-like organisms living in the cells of our own bodies, mitochondria. We tend to think of bacteria as nasty invasive diseases, and often they are, but not in this case. Mitochondria are like a disease we all catch from our mothers. It originated as an entirely separate organism, with its own DNA, or mtDNA, which is separate from the DNA of the rest of the cell. Some distant ancestor of most complex life absorbed them somewhere way back in the early days of evolution. They are the powerhouses of our cellular metabolism and we couldn’t survive without them.
However, they’re vulnerable to damage, especially from oxidation, and their DNA is not well shielded like our own. Irritatingly, like any organism, they produce waste, and this waste includes free radicals, typically an oxygen atom wandering around looking for a new molecular dance partner. Oxygen, despite its usefulness for metabolism, is very reactive and does a lot of damage to cells. Indeed, for much of the history of life on Earth, it was a toxic byproduct of almost all life, and organisms in the primordial oceans generated so much of it that two-and-a-half billion years ago they poisoned themselves, resulting in the extinction of most species.
The most successful of the survivors began using oxygen in metabolic processes, but that doesn’t change how reactive or dangerous it can be to life. Those little oxygen atoms slam around inside a cell till they bond with something, which can damage stuff like the mitochondria’s own unshielded DNA, causing degradation and mutation. Incidentally, this issue with oxygen and free radicals in general are why antioxidants are often recommended these days. Unfortunately, they don’t reach the places like the mitochondria, where free radicals are being generated, in time to stop them from doing damage. But the fact that so many people take these pills hoping that they will work is another reminder that while it’s still in the early stages, much like cybernetics, we’re already embracing the goal of life extension.
For cybernetics, one of our other options for combating aging, that ship also already sailed when we started embracing prosthetics, pacemakers, cochlear implants, and arguably even tooth fillings. I say that because, if you look at the mummies of the ancient Egyptians, tooth abscesses have been implicated in many of their deaths. Progress on these technologies can often get ignored because existing successful examples are now considered mundane and every day.
So the mitochondria start getting damaged and when they do, they produce less energy and enter into an abnormal metabolic state, and they and their mutant offspring eventually take over the aging cell and make it toxic to its neighbors. The notion that this may be the major cause of aging in people is generally called the Mitochondrial Free Radical theory of aging. We can’t be sure yet if it is the principle cause, but it’s certainly one of them and fixing this problem is called MitoSENS in the SENS schema. If we can find a way to replace damaged mitochondria, or even just kill the mutants, so non-mutants can reproduce instead, it’s possible that we could see a massive benefit to our lifespans and health.
This treatment is making a lot of progress too, on top of maybe being the most effective at slowing aging, and it is one of the reasons for a boom in optimism on the subject in recent years. mtDNA contains instructions for building just 13 proteins mitochondria need, but historically had about a thousand such genes. Those genes still exist, and evolution has apparently been slowly moving them into the safer nucleus, away from the damaging free radical production spots.
So, given time – a lot of time admittedly – this might have been solved on its own. But it suggests a pathway to a solution which is already in progress. There’s no magic here, we just identify the problem, free radicals causing a cascade of damage to mitochondria who produce them. How do we limit their accumulation, keep mitochondria protected from them, or remove any mitochondria that mutate to produce more free radicals?
Blog’s regular readers are probably thinking nanobots would be great for that, and indeed they would, as well as the other problem areas identified by SENS we’ll discuss, and its why I often say nanotech almost instantly solves a lot of our problems, much as commercial fusion power does. It’s just important to note that if we never get those or they’re further off than we might hope, we still have a ton of options on the table that can be implemented with biotechnologies that may be closer to hand. Among these is the option of cleaning up the junk inside of our cells. Our bodies are pretty good at breaking down, digesting, or removing stuff so it doesn’t accumulate too much.
One of these cleanup mechanisms is the lysosome, and we call this area of research LysoSENS. Your lysosomes are very good at their job, they’re basically big trash recyclers. They use enzymes to digest stuff, but some materials are resistant to these enzymes. The approach suggested here would be to re-arm them with additional enzymes. We know which things our current lysosome enzymes can’t handle, so we find enzymes in other organisms that can handle them and give them that ammunition. And we know those enzymes exist since, if they didn’t, we’d be ankle deep in such waste products by now, left over from the dead bodies of hundreds of millions of years of life on earth. We’ve also got some good early work on enzymes to treat congenital diseases, like Gaucher’s, caused by mutations that prevent victims from degrading accumulated lysosomal wastes that the rest of us already handle easily, via enzyme replacement therapy, which is essentially just giving them the missing enzyme in some form able to penetrate a cell’s membrane, enzymes they don’t happen to have.
The other junk is outside of cells, extracellular waste. The most well-known form of extracellular waste is beta-amyloid, a web-like material that forms plaques in the brains of patients with Alzheimer’s, and everyone else’s too, just not as much. It’s not just limited to mental degeneration: other kinds of extracellular junk are related to Type II Diabetes, certain kinds of heart failure, and many other conditions. Most of these extracellular bits of garbage are amyloids; hence, we call this area AmyloSENS. You’ll occasionally see people talk about a maximum lifespan folks might have that gets us all even if we survive everything else, and this might be one of those causes.
We don’t have an awful lot of folks who live past 110 years of age to build a nice sample from, but there’s some decent indicators most people who make it past 110 die from senile cardiac amyloidosis, a disorder caused by deposits of amyloid protein in the heart tissue. Needless to say we want to deal with amyloidosis, it’s both a killer and a quality of life issue. Again there’s a lot of ways to potentially clean up such garbage, same as there’s a lot of ways to clean a clogged water or sewage pipe. You can manually clean a pipe, you can make one that stuff sticks to less, you can flush it with something that dissolves the build-up, you can remove and replace the pipe, and soon.
Unsurprisingly, our bodies already do have a way of dealing with this, via our immune systems, so one approach being looked at is to simply augment our bodies’ existing immunological clean-up system. Our immune system goes after amyloids, and we’d like to give them catalytic antibodies to better break those amyloids down into manageable bits. This is one of the most promising new areas of Alzheimer’s research and, if successful, ought to be adaptable to other amyloids. Several promising antibodies have already been shown to remove such amyloids from the brain in human clinical trials; we’re now waiting to see what their effects are in keeping the brain alive and healthy in Alzheimer’s patients. So we’ve hit OncoSens – cancer basically, MitoSens – fixing our internal power plants so they stop trashing themselves when they break down a bit, Lyso and AmyloSens, junk removal and fighting ailments and conditions like Macular Degeneration, and Alzheimer’s.
The next we’ll discuss is RepleniSENS. Some of our cells either can’t be replaced or do so very slowly. The muscles in our heart as well as our skeletal muscles are good examples of this. Needless to say, we might be able to go the machine or clone route here and give yourself a new mechanical or cloned heart. This would be a lot harder to do with something like neurons however, which is where stem cell research comes in. Our pathways here though, in terms of current research, are in the treatments of diseases like Parkinson’s and continued improvements with transplants, both for supply and rejection concerns, our ideal organ replacement is one that matches the original, and while a close relative often fits that bill, you do better with organs genetically identical to your own.
It’s also worth remembering that even the best cell therapy or regenerative medicine won’t help if you get in an accident that severely damages a major organ. You might still have a youthful body when you’re 100, but that’s a bit wasted if you get stabbed in the kidney and we can’t replace that because we haven’t got any spares or you keep rejecting them. Again, all medicine is life extension, and being able to replace these organs or cells, or slow down how quickly they die, is one way to seriously extend average lifespans.
Of course, sometimes we want cells to die, again part of the core issue of cancer or OncoSens, but we also have ApoptoSENS. Senescence is when a cell stops dividing like it’s supposed to, but sometimes they just stop dividing and don’t die either. They’re basically dead wood, still taking up space and nutrients, producing waste, but not doing what they’re meant to. If they were to die, a healthy cell of the same type would divide to fill that spot. However, they just sit there, and need to be removed. Health problems caused by such cells include joint degeneration, type II diabetes, and aspects of cardiovascular disease and skin aging… think about what happens to our skin as we age, so research into this area could be funded for cosmetic reasons. Killing cells is easy of course.
But killing only specific cells and not other ones, especially ones of the same type that are healthy, is harder. It’s probably easier than assassinating bad mitochondria would be though, since whatever you’re using can target a whole cell, and it need not be something small enough to sneak into a cell to go after mitochondria individually. Options again are nanobots, specialized vaccines, targeted viruses, specialized toxins that bind only to non-functioning cells, and so on.
Most excitingly, there are already drugs that have been shown to selectively kill senescent cells in animal studies, and one of these has already begun human clinical testing. Our last one is a bit tricky. Our cells often need to link up and stay properly meshed to each other using a web work of extra cellular proteins. These either never get replaced and recycled, or do so very slowly. Functioning properly, they are responsible for everything from giving the lenses of your eyes or your arteries flexibility to keeping your ligaments strong. As they start to lose their elasticity, you can get problems like increasingly rigid arteries and higher blood pressure, not to mention any resulting organ damage.
The problem is caused by these various connecting and crosslinking proteins developing too many connections, often by interacting with blood sugar or other molecules floating about, but the sugar gives us our last treatment name, GlycoSENS. Specifically, in humans it appears to be a molecule called Glucosepane, there were some setbacks early in this area because lab rats have a different and simpler molecule that causes most of their equivalent issues, one that can be broken up by medications more easily than the comparatively complex glucosepane. Options suggested thus far would be to find a drug or enzyme that does it, or hit people with large doses of a protein that broke up these crosslinks and could then be easily digested in turn.
None of these solutions are going to be a simple fix, and as you can see, they’ve got a lot of overlap with areas we are working at, and making progress towards addressing. Patience is needed, but optimism is not inappropriate here either. Quite to the contrary, it’s that weird cynicism about being able to cure aging that is irrational, and why it’s important to realize that it’s a blanket concept for mostly unrelated issues. Indeed, if we nail down all seven, people might live centuries, and we might find seven more that only cause problems after centuries.
Those might prove to be easier as a result of our experience, or may prove even more difficult due to their novelty. Evolution, after all, has no reason to work on design problems that only get fatal after a few centuries. One has to acknowledge, a machine that works constantly for many decades before breaking down is hardly one deserving much criticism given that not many of our devices last that long. Now, does this mean we’ll all live to a thousand years, to match or exceed Methuselah? No — at least, not without a lot of work, not right away, and not from these therapies alone. Again there’s a lot of work to be done and we’ve really only just gotten started.
We can’t be sure our picture of aging is correct. There are many theories, each with decent supporting evidence and adherents. We need to know which one, if any, is right, and we need to abandon the notion that this is a subject we can never master, even if it takes several centuries. I don’t see any reason to think that’s so, but even if it were, we’ve never been afraid of challenges and this would be a bizarre one to suddenly shy away from. And even if we’re wrong and it truly does turn out impossible for some reason, I’d rather have still tried anyway.
Everyone’s got a right to their own perspective but the usual reasons for not trying are that it’s unethical to extend our lives, because it’s unnatural, or that we’ll get bored. Frankly I consider both fairly dubious assertions, we’ve been doing life extension for a longtime already and threw natural out the window the moment we started growing crops. If we hadn’t, I’d be chasing a mammoth with a spear right now instead of sitting at my desk pressing strange square buttons to communicate with people living on other continents.
As to boredom, I personally can’t ever imagine getting bored enough to want my life to end. Heck the backlist of books I’ve been meaning to read alone would set me up for a decade or two at this point, but there is a pretty obvious solution for how one can cease to be bored with life, and I’d much rather get to pick when that happens. And in any case, ask yourself: would you rather be bored to death at 150, or have Parkinson’s disease at age 70? I’ve never understood either set of reasoning and fortunately many other folks don’t and I think an increasing number won’t either as life extension becomes more and more foreseeable.
One of the groups leading the way on this is SENS Research Foundation, and I’ve mentioned them a few times before on the blog. Indeed, we did a very successful fundraising drive for them last year, so when the time came to do this article I sat down with two of their founders, Aubrey de Grey and MikeKope, and picked their brains on the topic. One of the first things that struck me, as we chatted, was how we all constantly encountered that sort of strange resistance to the concept people often have. I suspect that here at EduQuarks, that’s less prevalent since we’re generally focused on the future and are optimistic about it.
Hopefully you now share our optimism on the topic, and see now that it’s an area that’s certainly full of challenges, but probably manageable ones if we’re determined enough. There are other groups looking into this, other approaches, some of which we’ve discussed before too, but there was so much information just for the SENS approach alone that I wanted to focus on them today and to thank them for their help.
For our folks living on the eastern side of the Atlantic, they are having a conference in Berlin early in the upcoming spring. If you can’t go or want to know more now, I’d really suggest their website, SENS.org
They’ve got some phenomenal resources, from introductory material to more advanced materials which gets into much deeper detail than we could in one article. I’m particularly fond of a short article series they did that’s got some wonderful animations, some of which they loaned to us for today, and were narrated by Edward James Olmos, best known for Battlestar Galactica, or my favorite film, Blade Runner, which was one of my inspiring influences growing up for this topic and many others. There’s a lot of resources on that website to learn more, so make sure to check it out. And if you really want a deep dive into the science of SENS, check out Ending Aging, a full-length book on the subject by Aubrey de Grey and his research assistant MichaelRae.
All right, next week we’ll be back to the Earth 2.0 series. When we last visited there we were discussing colonizing the oceans and trying to live surrounded by water, in next week’s article we’ll do the reverse, and look at how we might bring water to the deserts in “Reclaiming the Deserts”. The week after that, we’ll be visiting a place more barren than even our harshest deserts, as we return to the Moon to look at how things may play out as colonization proceeds and we begin getting some serious civilizations up there, in “Battle for the Moon”, and we’ll take a look at our Book of the Month, “Artemis”, the newest novel by Andy Weir, author of “The Martian”.
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