“[...] the most promising ways to postpone aging are by disrupting the pathways underlying it, just as we do for specific diseases.” (de Grey, p.22) That line sums up an important element of strategies for engineering negligible senescence (SENS) in Aubrey de Grey’s book Ending Aging, published in 2007. The book outlines the straightforward sense in disrupting the pathways that cause us to age: by engineering the damage of aging out of our biology after the body has experienced the damage, but before the damage accumulates to deadly levels.
In the various sections here, I’ll be going over why we should think this can work, why we should think this is thorough, what the big picture looks like, and what we should be doing because of it. These are exceptionally key life-and-death concepts that we all need to help turn into common knowledge.
When I was in high school in the 1990s, as I recall, a segment of one of our classes focused on aging and lasted for a few weeks. Our teacher left us with the impression that aging was impossibly mysterious and probably always would be. He seemed to take a somber tone when talking about it.
Maybe I sensed that he was acting a bit differently because he merely had the flu, was distracted, or I was reading him wrong – I don’t know. It seemed to me that he didn’t really want to go over it much. I could have sworn that I sensed an air of anxiety from him over the issue, as though, perhaps, he didn’t know how wise it was to paint this bleak futility into the heads of these youth. Or maybe the trauma that death has already caused him in his life and his own terror in the face of it had crippled his intellect on the matter. Maybe it was that he knew that students tended to become extra cocky and flippant about this issue that he was so sure was a futile waste of time, and a closed case.
The devil’s-advocacy reflexes among us youthful sprites inevitably did kick in. We tried to argue around it, and our best shots seemed to be dismissively batted away.
'No, no you can't do that, telomeres will always end us, there’s no way around it. The havoc wreaked by metabolism, mutations, and things throughout the aging process is just too much. Solving it is an untenable paradox. There’s no reason to think that tools can become that specialized. That’s how it works, it’s dirty, too complex, and unfixable.'
I didn’t think so. I thought there must be a way. I was betting from what I knew of him and could see of the subject that he was going to end with some interesting insight that left us all metaphorically applauding with optimism and determination to consider tackling this kind of field, but he didn’t. My teacher didn’t seem to be a Columbus or a Spartacus, a Newton or a Pasteur.
I wish I would have kept thinking about it then. I wish my science teacher, and science teachers around the world, had possessed more scientific and critical-thinking courage to instill more of a drive in us students to take the challenge on, daunting though they were convinced it was in those days.
The way forward to stopping aging is clear, yet people still treat it like it’s not.
That was only 20 years ago. Since then the reality of what humanity knows about aging and its surrounding issues has been changed through a multitude of scientific insights, from a variety of researchers and organizations around the world. Some of these insights are harder to grasp, but potentially no less tenable than others. Some of them help bolster hypotheses of aging that have other complications and holes.
There is a simplified roadmap that sums up most every path that can be taken to indefinitely extend life, which we will go over a bit later. The clearest of the ways forward, leading the charge, is the concept of eradicating the damage that is building up in our bodies and killing us, as outlined and taken on by SENS.
Regardless of which path(s) we take, one way or another we have to go through, around, over, under, or some other way to obviate the effects of this damage. And yes, we do have to do it. Life is far too mysterious and incredible to coddle the grave and yawn at the future.
If there were semi-understandable reasons to excuse away potential paths and hypotheses to defeating aging in the 1990s and before, the first decade of the 21st century has been the herald of a new age in understanding of aging. It has been over a decade now since there was an excuse for teachers to discourage students from thinking about cures for aging. We can’t accept procrastination as an answer. Most teachers haven’t researched the field well enough or thought it through yet, as exemplified by people like Professor Bret Weinstein who, in 2006, stated that
“[There is] the very real possibility that no solution to the senescence problem exists at all. Indeed, that scenario seems highly likely, as any intervention massive enough to do the job would naturally tend to create bigger problems than it solves.”
That kind of mentality fell especially behind the times after 2007, when the clear reasoning for taking on the forms of damage outlined by SENS was meticulously spelled out in sociological and scientific detail, and published in layman’s terms, in Ending Aging.
In these skeptics’ defense, though, everybody can’t be expected to catch on to new truths and revelations all at once. The Romans brought the world an architectural revolution, building with concrete and new frameworks for hundreds of years before much of the rest of Europe caught on. Copernicus knew that it was hard to change prevailing mindsets: his new heliocentrism wasn’t taken up more widely for decades.
Now every person that has come to understand the importance of the insights and ways forward outlined in Ending Aging has to become a teacher. Every person that understands this groundbreaking way forward is now responsible for teaching it to those that don’t.
As de Grey writes, and as the rest of the book explains,
"I couldn't think of any more categories of damage! Try as I might, I really couldn’t. There were a couple of other examples of molecular changes that accumulated throughout life, but I had reasons to believe that they were in the same boat as non-cancer-causing chromosomal mutations: they might be harmful if we lived hundreds of years, but they very probably weren't harmful in a normal lifetime. Other than that, everything I had learnt about during my five years of study and conference-hopping seemed to be covered." (41)
The following table is from "The seven parts of SENS" (43).
"As I mentioned […], there may well be other problems that will emerge if we succeed in solving all of these and thereby live a great deal longer. I felt, however, that my list might very well be comprehensive enough to give a few decades of extra life to people who are already in middle age before we start the treatments." (42)
I and growing communities of people like me are firmly convinced that we must embrace this way forward and help get it done without delay.
I think that taking the fallibilist approach is the best way to go. That is, you can be passionate, active, and dedicated to a concept and still be prepared to be wrong about it if the data change down the line. We can’t afford to be meek about it just because SENS might be wrong. We must do what it takes to execute its components like our lives depend on it.
Proofs of principle
So, what reasoning do we have to believe that we can even humor the notion that it might be possible to remove or reverse these forms of damage? There are multiple, straightforward, convincing reasons that are clear to see.
As noted in the above table, one of the forms of damage that accumulates in our biology and ages us to death is junk inside cells, the buildup of lipofuscin. Lipofuscin particles are bits of material that, for various reasons, cannot be easily digested by our cellular recycling centers, the lysosomes.
As noted in Ending Aging,
“After a few decades of work, victims of three of the most common [lysosomal storage diseases (LSDs)] are now being successfully treated with such therapies. There are, for instance, about four thousand people now living normal lives despite having Gaucher's disease, thanks to regular injections of the lysosomal enzyme that their cells are unable to produce for themselves. The drug development process has been reasonably clear, although technically challenging. In one disease after another, scientists have identified the enzyme whose absence cause the disorder; modified it in various ways to allow it to be injected, taken up by cells, and delivered to the patient's lysosome, where they function exactly like the same enzyme does in the rest of us when it is produced by our own cells; and watched as symptoms have disappeared, lives have been extended, and victims have been enabled to live the life that the rest of us take for granted.” (126)
“Again, one potential solution is already in use in the LSDs: the use of molecules of the sugar mannose 6-phosphate, which is recognized and taken up – along with its cargo – by the lysosome.” (131)
When it comes to another of these seven types of damage, junk outside of cells, extra-cellular damage accumulation like the amyloid plaques involved in slowly killing us through dementia, Ending Aging explains the following:
“Through careful sifting of the data, scientists managed to collect some preliminary information suggesting that, despite the horrors of inflamed brains in a few patients, immunization with beta-amyloid fundamentally does work as a therapy in humans.” (153)
“[...] old Caribbean green monkeys given beta-amyloid vaccination exhibited huge (66 percent) reductions in beta-amyloid levels in the brain, and a complete absence of plaques, and that the dense tangling-up of neurons' supporting glial cells usually seen in human Alzheimer's patients was considerably reduced. This is an important piece of supporting evidence, because these monkeys develop some Alzheimer’s-type pathology naturally as they age, and are much closer relatives to us than any mouse.” (155)
Work on this continues.
As recently as January of 2014, with the help of visionary Dietmar Hopp,
“[A] new injection of cash is specifically earmarked for the clinical development of another antibody that AC Immune has discovered and successfully tested in animals. This new therapy targets tau, the other tangle in the brain that has also been implicated as a trigger for Alzheimer's.” (http://www.fiercebiotech.com/story/billionaire-backs-new-
In discussions with many of the thousands of people that I’ve talked to about this life-and-death cause over the years, I like to say things like,
“And one of the seven forms of damage is the accumulation of lipofuscin in our lysosomes, the cells’ recycling centers. Lipofuscin is a material that our lysosomes can’t break down, and so it accumulates. It’s like how when you vacuum your carpeting, many times, it won’t pick up things like pennies and bread ties. If you never picked those things up, then after 20 years of vacuuming, your floor would be crowded with them, making it harder to live. If we can get that lipofuscin out, then our cells can be healthier and help us live longer. Good news in that way is that there are conditions such as rare lysosomal storage diseases, that have already been worked on with success in laboratories around the world, and places like SENS are already working on the aging aspects of it.”
Another of the things that I’ll often say to convey this kind of crucial insight is,
“For example – and I can understand how this might be hard to believe, but listen to this – they have already found a way to clear the amyloid plaques of Alzheimer’s disease out of the brains of monkeys with a vaccine; it’s just that it caused some people to die in clinical trials, and so it was pulled until further research is conducted. With more people going into educational outreach and research, and helping to fund these kinds of things, this kind of research could take our progress to the next levels much sooner. The work going into this is all supported by and reported on through the movement for indefinite life extension (MILE) – a Facebook gathering that is building support for people and projects working directly or indirectly toward these goals. Find us there and help us spread the word.”
You can use approaches like these or use the data to craft ones that work best for you and the people you talk to. If you need help, find a related life-extension community and ask away. Find me if you want; I’m around, and I will be happy to help you.
You’ll find plenty of rebuttals like these in related topics and discussions. For example, in a response to Dr. Charles Mobbs talking about how there isn’t even one proposed SENS modification that could be carried out by science (http://www2.technologyreview.com/sens/docs/mobbs.pdf), Aubrey de Grey points out that:
“immune-mediated removal of neural amyloid (extracellular junk) and pharmacological un-stiffening of the artery wall (extracellular crosslinks) were demonstrated in rodents several years ago and are in clinical trials.” (http://www2.technologyreview.com/sens/docs/mobbs_rebuttal.pdf)
I like this excerpt from Ending Aging:
“The difficult thing about designing an AGE-breaker drug is not that there's any lack of chemicals that can break apart a given cross-link; the problem is to come up with something that won't also tear normal, healthy proteins to shreds in the process.” (193)
It alludes to the notion that we are not plagued by complete and utter ignorance on how to even begin to imagine ways through with these various damage challenges. Rather, the solution is in the fine-tuning. The solutions are probably already there. Now let’s tease them out of the chemistry.
For another of the seven challenges, using allotopic expression to combat mitochondrial mutations, a 2010 study reported that
“Two important pathways that direct proteins into the mitochondrial inner membrane and matrix have been known for many years. The identification of numerous new transport components in recent proteomic studies has led to novel mechanistic insight into these pathways and the discovery of new import pathways into the outer membrane and intermembrane space.” (http://www.sfb746.uni-freiburg.de/Publications/2012/Pfanner/schmidt_2010.pdf)
Ending Aging devotes two entire chapters to the subject instead of one like the rest. Read it, learn it, open your reticular activating system to it, and get these kinds of insights flowing around in your head so they can come out through your mouth and your aptitudes.
Regarding another of the seven forms of damage, Dr. de Grey proposes that we replenish cancer-prone areas with stem cells that lack telomeres. Impossible? Too hard? How would we scrape the cells out of so many of the parts of our bodies and restock them with stem cells? Well, read the book. It gives you an excellent look at the issues, and leaves you with a big bibliography, your imagination, and the current forward march of science and technology to work with. The mind-blowing mysteries of the universe need you to read this book as they await your arrival.
Here are some excerpts of examples of how it can be done, which are not hard to find and which the book points out for us.
“Bone marrow transplantations are, of course, already a common and nearly routine procedure, not only for DKC sufferers, but also for patients with a range of blood disorders, cancer patients who have lost their bone marrow to radiation therapy, and many others.” (303)
“[Dr. F. Charles Campbell’s] team extracted stem cells from mouse intestinal tissue, wiped out the cells from small stretches of the colon, and then repopulated the tissue with stem cells, which differentiated into all the appropriate cell types and made fully functional new tissue.” (305)
These are just a few of the examples. Who really thinks that humanity won’t eventually be able to figure out and control every form of damage? Even if we do find out that there are more than seven types, we’ll accept those challenges, too.