Ending Aging
MUST WE AGE? A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Recent progress in genetic manipulations and calorie-restricted diets in laboratory animals hold forth the promise that someday science will enable us to exert total control over our own biological aging. Nearly all scientists who study the biology of aging agree that we will someday be able to substantially slow down the aging process, extending our productive, youthful lives. Dr. Aubrey de Grey is perhaps the most bullish of all such researchers. As has been reported in media outlets ranging from 60 Minutes to The New York Times, Dr. de Grey believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirely—technology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite future—is now within reach. In Ending Aging, Dr. de Grey and his research assistant Michael Rae describe the details of this biotechnology. They explain that the aging of the human body, just like the aging of man-made machines, results from an accumulation of various types of damage. As with man-made machines, this damage can periodically be repaired, leading to indefinite extension of the machine's fully functional lifetime, just as is routinely done with classic cars.
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- We do. Read Ending Aging by aubrey de gray
- It's actually a collection of theories known as the mitochondrial theory of aging: https://en.wikipedia.org/wiki/Mitochondrial_theory_of_ageing
It's a little confusing to look into, because there's a bunch of separate theories about the nature of aging that all involve mitochondria in some way. You will find news articles saying that the mitochondrial theory of aging was discredited because of some study done, but when you look into it, it turns out that what was shown was that some specific variant of the theory was insufficient for accounting for all forms of aging, which is not the same thing. Each mitochondrial theory of aging is a theory about one pathway by which mitochondrial function or dysfunction results in aging damage, the reality is that many or all of these theories are true and aging is the aggregation of damage from all of them, and more pathways we have yet to discover.
Generally speaking, the vast majority of aging damage comes, directly or indirectly, from the accumulating damage from healthy operation of mitochondria over long periods of time, or the accumulation of cells with unhealthy mitochondria that produce damage more rapidly. The ELI5 is that mitochondria produce free radicals, free radicals chemically alter basically anything they touch, and aging is simply the slow accumulation of intercellular and intracellular damage, and if you follow the history of these molecules back to when they diverged from being in a healthy state, it is almost always the result of oxidative damage (e.g. free radicals of the sort produced by mitochondria).
Another ELI5 way of looking at it: you may not know this, but mitochondria only live a couple of days. They are constantly being refreshed in your cells because of the severe oxidative stress they undergo. They also sometimes break or leak, letting those reactive oxygen species into the cell and causing damage. Aging is the accumulation of this damage.
But I said aging was "downstream of" mitochondrial dysfunction. That's because not all aspects of aging is due to reactive oxygen species leaking out like I seemed to claim above. That's just one example. There are cells in your body that have lost all mitochondria, often due to a freak genetic mutation in the mitochondrial DNA of that cell. Surprisingly these cells don't die, but rather switch into a mode of operation where they slow down and live off energy extracted from the intercellular medium and converted into ATP by various molecular systems embedded in the cell membrane. These processes, as it turns out, free radicals out of the cell during operation, spewing reactive species into the body. This ends up being responsible for hardening tissue, lack of energy, and many other symptoms of aging. But the root cause? The mitochondria stopped working in that cell, so still a mitochondrial issue.
Or, the aging of heart cells and the hardening of arteries is largely due to the collection of dysfunctional lysosomes that are full of garbage they are unable to break down. These clutter cells, harm their efficiency, and eventually have enough collective effect as to make the tissue as a whole less viable. Leading to heart attacks and other cardiovascular disease, which is the leading cause of age-related death alongside cancer. Want to guess what these defective lysosomes are full of? Mostly undigested mitochondria, specifically the highly damaged structures of mitochondria that suffered too much oxidative damage from long operation.
Oh, and what about cancer? Well cancer needs A LOT of energy to keep replicating, and so it should be no surprise that many of the mutations among common cancers have to do with genes in the nucleus affecting mitochondrial function, or the various signaling pathways between the nucleus and the mitochondria of the cell. This article covers some of the ways that cancer uses mitochondria: https://pmc.ncbi.nlm.nih.gov/articles/PMC4371788/
The best lay introduction I know is "Ending Aging" by Aubrey de Grey and Michael Rae. The book is meant to be an enumeration of all the things that need to be done to biologically reverse aging, but ends up being more than 80% about mitochondria and mitochondrial dysfunction, because of its out-of-proportion impact on the aging process.
- > What got you interested in life extension?
Immediately when I first heard about it I thought, wow, this is fantastic, because death is a really bad thing. I believe it was mostly reading the book Ending Aging by Aubrey de Grey, although I may have heard about some related ideas on various websites before that.
> And how long would you want to live for?
Certainly at least a couple hundred years, and by that point I'd have time to think about how much longer I'd want. I don't really see a reason why I'd want less than infinite time if it were possible.
> I’ve never understood the philosophy behind life extension research, because to me it seems like a case of spending a lot of resources in the hope of improving something that isn’t really broken.
I've spent several decades working really hard, or studying. Although I hope I'll have a great time in the next several decades, I sure do want more.
Also, I have many things I want to do that I know I won't have time to do in one currently normal lifetime. There are several projects like books I'd write that I will probably not get a chance to do, because there are so many other things I want to do also.
Basically the rough outline of my schedule for the next 40-50 years is pretty packed. Obviously I'm going to prioritize and so a bunch of things will be pushed off the list, but I'd really like to do all the things on the list, plus have plenty of time for general entertainment, social life, and so on.
- I don't think Aubrey de Grey is a good guy, and for anyone that is seriously interested in longevity research, it is known that he is mostly an old mascot that has kicked off a lot of (public, though not so much scientific) discourse in that field, but he and his foundation hasn't produced much by themselves.
Having said all that, the dismissal of longevity(/rejuvenation) research in general by the author (and many of the comments here) is incredibly shallow. While Aubrey de Grey highlights his mitochondiral research in his book "Ending Aging"[0], he never claims that it is a silver bullet for aging and most off the book revolves around different parts to the puzzle that have all to be solved in order for consistent rejuvenation to succeed.
A few years later "The Hallmarks of Aging"[1] (which outlines a similar approach to the book) was published in Cell and is widely recognized as a milestone paper and "roadmap" on what problems need to be tackled on the road to longevity. There are also now many biotech startups tackling exactly those problems outlined, producing real drugs that are currently in trials (e.g. Unity Biotechnology[2]), and the rate of more of them popping up is only accelerating.
I could try to write even more here to convince you that longevity research is a worthwile pursuit (and not just vaporware), but it's probably better if you read up on the topic for yourself, for which I can strongly recommend /r/longevity[3] and the resources listed there.
[0]: https://www.amazon.com/Ending-Aging-Rejuvenation-Breakthroug...
[1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/
- For a counterpoint to the confidence, but still a very high-confidence prediction, Aubrey de Grey has recently estimated a 50% chance that we'll hit longevity escape velocity by 2036. That is, enough treatments will be available to people such that they can expect their lifespans to be Y, an increase from their previous X. But before they hit Y age, there'll be new treatments developed they can take that extend expected life age even further to Z, and so on, until we arrive at general treatments that extend life indefinitely.
Aubrey is the foremost expert in the whole field of longevity research as far as I'm concerned, so I don't have any reason to be more or less confident than him about any aspect of it. If you haven't read it, his Ending Aging book covers a lot of details. It was published in 2007 but has still held up, especially with overall strategy. Apart from the various medical developments since then, another encouraging sign is the increase in newly formed companies in the space, lowering the need for philanthropy/government grants. https://agingbiotech.info/ has a list
- I've never created a reading list, so this was a fun exercise.
Programming:
* Analyzing Computer System Performance with Perl::PDQ - Gunther
* The Mythical Man Month - Brooks
Philosophy:
* A Journey Around my Room - de Maistre
* Anger, Mercy, and Revenge - Seneca
* Schrödinger - What is Life?
* Man's Search for Meaning - Frankl
* Essays - Montaigne
* Ethical Intuitionism - Huemer
* The Consolations of Philosophy - de Botton
* A Manual for Living - Epictetus
* Meditations - Aurelius
Psychology / Meaning / Purpose / Science:
* Purpose and Meaning in the Workplace - Dik, Byrne & Steger
* The Case Against Education - Caplan
* Selfish Reasons to Have More Kids - Caplan
* Dawkins - The Selfish Gene
* A Confession - Tolstoy
* Enlightenment Now - Pinker
* The Better Angels of our Nature - Pinker
* The Improving State of the World - Goklany
* The Skeptical Environmentalist - Lomborg
* Religion for Atheists - de Botton
* Ending Aging - de Grey
* Gut Feelings - Gigirenzer
Fiction:
* Heart of Darkness - Conrad
* Candide - Voltaire
* Brave New World - Huxley
* Selected Works - Goethe
* 1984 & Animal Farm - Orwell
Politics:
* Obedience to Authority - Milgram
* The Problem of Political Authority - Huemer
* The Communist Manifesto - Marx
* Socialism - von Mises
* Just One Child - Greenhalgh
* The God That Failed - Crossman
* Death by Government - Rummel
Thought-provoking:
* Free to Learn - Gray
* The Beautiful Tree - Tooley
* Education and the State - West
* The Machinery of Freedom - Friedman
* Against Intellectual Monopoly - Boldrine & Levine
* From Mutual Aid to the Welfare State - Beito
* The Not So Wild, Wild West - Hill
* More Guns, Less Crime - Lott
* Race & Economics - Williams
* Emancipating Slaves, Enslaving Free Men - Hummel
