Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime

I just finished reading Dr. Aubrey de Grey’s Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime (2007), it was an accessible introduction to the biology of aging, and a way that it might be defeated. By default, I am skeptical about anti-aging techniques or claims of some sort of fountain of youth. I’ve heard de Gray’s idea on a podcast, and watched his TED talk. It sounded reasonable, but I wanted to learn more about the science to have a more informed opinion, so I read the book. The plan is referred to as SENS (Strategies for Engineered Negligible Senescence). After reading the book, I think it is a plausible plan for an approach to reverse the effects of aging. I’ll summarize the idea and highlight some things from the book that weren’t covered in de Gray’s TED talk or podcast interview. The central assumption of the book is that aging is the accumulation of seven types of damage: Mitochondrial DNA mutations Nuclear DNA mutations Intercellular junk (e.g. lipofuscin) Extracellular junk (e.g. beta amyloids) Glycation (stiffens tissues leading to stroke, heart disease, etc.) Cells not dying when they are supposed to (e.g. cancer) Cells dying when they are not supposed to Each of these types of damage is covered in detail in the book, along with one or more possible solutions. For example, number (7) can be treated by using stem cells to replace the lost cells, this has already been demonstrated to work, but there are political hurdles to stem cell research. A comprehensive plan to completely reverse the effects of aging may change this. Another example is (1), he explained how mitochondria, which generate energy in the cells, have their own DNA, and they produce lots of reactive byproducts that damage the mitochondria’s own DNA. This can be fixed by saving a copy of the mitochondria DNA in the cell nucleus, where it is about 100 times less likely to mutate. Some forms of algae already do this, so it is not without precedent. An interesting one is (5), or glycation, which is the process that leads to the gradual stiffening of tissues. Glucose in the blood sometimes sticks to proteins and causes them to tangle up, this is what happens with caramelization, but at a much slower rate. There are already biotechnology companies that are working on drugs that target glycation endproducts, it is possible to undo the glycation damage, further research is needed before all forms of glycation are fixed, but it is simply a matter of money and time. All of the types of damage but (6) seemed relatively straightfoward to solve. It is (6) that is the most troublesome. Assuming all the other types of damage are satisfactorily solved, cancer is still a big problem. In order to keep a human healthy indefinitely, you’d need to prevent cancer growth. There are many types of cancer, and within cancers there are many types of cells, but they all have something in common. They have an active telemorase enzyme, which is what replenishes the telomeres (segments of junk DNA at either end, which shorten with every cell division). Since cancerous cells’ DNA keeps getting it’s telomere’s restored, they can reproduce indefinitely, this is the main threat of cancer, it can grow forever, until it disturbs its surroundings (your healthy tissue). Aubrey de Grey has a solution for this, but it is the most extreme of the book: Remove all telemorase genes from all cells of the human body. This means that the remaining human body only last about 10 years. Since nuclear DNA mutations are inevitable, and sometimes lead to cancers, having all your cells be unable to replenish their telomeres means that all cancers would eventually hit a wall (after about 50 cell divisions). Then, to solve the problem of your cells running out of telomeres, new stem cells could be engineered with a copy of your DNA (minus the gene for telemorase), and you could top off your stem cell supply every 5-10 years. The problem with making all your cells immortal is that cancer will eventually win. By making all your cells mortal, even cancerous ones, you can continue to get SENS therapy until you no longer want to stay alive. If aging is indeed the sum of those 7 types of damage, then this panel of therapies will enable humans to live indefinite youthful lifespans. So it appears possible to keep humans alive as long as they want to live, and prevent the decay and the eventual death of the body. This is fantastic, as the majority of healthcare spending is due to this decay. If SENS (or something like it) can be developed afforably, it would save nations trillions of dollars in healthcare and social security spending, as well as give people the choice to live for centuries. There is a follow up question that the book didn’t address, but it was outside the scope of the book, so I’ll address it here: [...]

The basic strategy is to bootstrap: figure out how to repair the age-related damage that we know about today, and use the extra lifetime this gives us to learn how to repair the damage that will develop as we live longer and longer lives. So if you reach the age of 200, say, the damage that has to be repaired is the damage that occurs to get to 100, plus whatever becomes an additional problem between 100 and 200, and so on. I think the basic strategy is quite sound, given the exponential progress in technology and especially bio-tech that we are seeing today. It is pretty common to hear researchers say that they can do more in a year today than they could do in 10 years previously, because the tools and our knowledge are both so much better. So once we can get to a point where we can extend current lives by 20+ years, there is a good chance that no one will die of old age ever again (except by choice). When I talk about this, one of the immediate concerns I hear is for the planet and running out of resources. Personally, I am convinced that when this problem arrives we will solve it, and that there are a variety of ways that this could be done (much lower birth rates, higher density on this planet, moving into space and/or to other planets), so I am much more concerned with curing aging. I don't want to see any more of my friends or family die, and I would like to enjoy life as long as I want. So I am all in favor of this program! The book is divided into three sections. One that talks about the problem of aging and treating it as an engineering problem to be solved; one that talks about the known issues that have to be solved and possible solutions; and one that talks about what each of us can do to contribute to solving the problem. The central section of the book is excellent, a superb treatise on why we age and the damage that causes age-related problems. It was also extremely encouraging to see the progress we've made in understanding these processes, and the progress we've made in finding ways to repair them. I hope this book will help more people realize what is possible, and that we need to push on this to get it to happen sooner rather than later. Highly recommended.

A great book for intelligent people without any background in Biology. It made me want to take action helping the SENS foundation

Excellent book, Aubrey knows what he is talking about and I leanst many useful things, especially the caloric restriction experiments.

Ending Aging may one day be regarded as having made history. And it is fun, provoking, and informative. Its starting point itself is eye-opening: aging isn't built into our bodies, it only results from a gradual breakdown that evolution hasn't found efficient to equip us against, picking reproduction as the preferred path for gene survival. De Grey adds that this breakdown can be fixed. Science will soon be able to engineer eternal youth, he asserts - yes, not just slow aging down but actually set back the clock. This would apparently require fixing decay in seven broad areas, for which he details the solutions. To me, a complete layman, four of the proposed solutions seem in the process of advanced medical research, two look farther off, and one, dealing with cancer, sounds somewhat unpalatable if perhaps credible (requiring regular cell transplants to a multiplicity of organs). De Grey is not originally a biologist, but a computer programmer. He says his outsider status is an advantage. Sounds suspicious? Perhaps, but he published revolutionary research on the DNA of mitochondria (the part of the cell that generates the energy on which we live) and their role in aging; this was peer-reviewed and acclaimed by the scientific establishment. He was awarded a PhD for it at Cambridge, where he works. Ending Aging says its goals can be achieved in 25 years. Considering the impotence of big pharma and the propensity to blunders of public government (viz. the stem cell controversy, which is detailed in the book), this sounds doubtful. But incredibly, one big hurdle to pursuing the requisite research seems to be that a number of people don't actually want to end aging. This is where De Grey turns from scientist to advocate. Apparently, the fear is that ending aging would cause grave disruption to the environment and existing social structures. So what?

Die Kernaussage für mich: Das Altern im negativen Sinne (Falten, Immunschwäche, Organversagen, Arterienverhärtung...) ist kein magischer Prozess, den der Körper beschließt oder anschaltet sobald er das reproduktionsfähige Alter überschritten hat. Es ist ein Vorgang, der daraus resultiert, dass mehrere Prozesse von Geburt an unsauber laufen. Da deren Abfallprodukte in Krankheiten münden (z.B. Alzheimer, Herzinfarkt, Parkinson, Schlaganfall), aber in einer normalen Lebensspanne, sagen wir 40 Jahre, praktisch keine Rolle spielen, machte es für die Evolution keinen Sinn, diese Prozesse zu säubern. Wer also heute 80 wird, stellt schlicht und ergreifend fest, worum sich die Evolution nie kümmern wollte oder musste. Heute macht das Sinn diese Themen anzugehen. Diese Erkenntnis war für mich wichtig, weil sie befreit von dem Denken, dass Altern und Tod wichtig, notwendig und unangreifbar sind. Dieses offene Mindset ist für das annehmen des Buchinhaltes wichtig. Aubrey de Grey nähert sich frontal dem Tabu Thema unendlichen Lebens. 80% des Buches beschäftigen sich mit einem für den Laien verständlichen Überblick über den aktuellen Stand der Forschung zum Thema Schäden durch Altern" und möglichen Ansatzpunkten, hieran in den nächsten Jahrzehnten erfolgreich weiter zu arbeiten. Er geht dabei nicht davon aus, dass wir alle unsterblich werden, räumt dem Kampf gegen das Altern aber eine 50% Wahrscheinlichkeit für hierfür notwendige erste Erfolge in den nächsten Jahrzehnten ein. Auf den ersten 40 Seiten erklärt er, warum er dieses Buch schreibt wake up, aging kills!", welche Ziele er verfolgt und wie er gedenkt, den ggf ablehnenden Leser im Laufe des Lesens Schritt für Schritt zu überzeugen, dass eine massive Lebensverlängerung nicht nur sinnvoll, sondern auch möglich ist. Für die Gruppe von Lesern, die sich ohnehin mit radikalen technischen Zukunftsszenarien á la Ray Kurzweil oder Science Fiction Stories von Bruce Sterling anfreunden können, dient dies als freundliche Einleitung in den medizinischen Kern des Buches. Die Meisten Leute stehen dem Thema radikaler Lebensverlängerung intuitiv ablehnend gegenüber. Diese wesentliche Zielgruppe seines Buches möchte ich animieren, sich von dieser recht kontroversen Einleitung nicht abschrecken zu lassen, sondern sich vorerst dem Kern des Buches zu widmen. Man muss nicht an Aubreys Erfolg glauben, um die Beschreibung des Status Quo der Forschung und möglicher Ansätze als wertvoll zu empfinden. Obwohl der Großteil des Buches sich mit den biologischen Abläufen im Menschen beschäftigt, ist es für den akademisch interessierten Laien doch lesbar. Und falls nicht jedes Detail verständlich ist, gibt de Grey für die meisten wichtigen Zusammenhänge sehr anschauliche Analogien aus dem gewöhnlichen Alltag. Trotzdem denke ich, dass auch der wissenschaftliche Teil des Buches für Fachkundige nicht plump wirkt, sondern interessanten Lesestoff darstellt (so weit mir das als Fachfremder zusteht zu beurteilen). Ich schätze das Buch insgesamt für einen sehr selbstkritischen, humorvollen und aufrichtigen Stil und hoffe, dass es zur öffentlichen Diskussion des Themas beiträgt.

The concepts are presented so elegantly and it's a road map for anyone who want to look into possibilities in the field of anti-aging. Good work, highly appreciate it.