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RichardJActon50

I have a reading list and recommendations for sources of ongoing news in the longevity/immortality/life extension space in the show notes for the recent special episode of my podcast where my co-host Michael and I discuss ageing and immortality. We are both biology PhDs, my background is in the epigenetics of ageing and Michael's bone stem cells.

https://www.xenothesis.com/53_xenogenesis_ageing_and_immortality_special/

I should add "Immune: a Journey into the Mysterious System that Keeps You Alive" to that list actually.

In particular from that list I recommend these for 'coming at biology from a physics perspective':

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Willa10

Thank you for the resources! I've queued up XenoThesis 53: Ageing and Immortality Special on my podcast player.

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This is a linkpost for https://immortalityisgreat.substack.com/p/have-you-considered-getting-rid-of?sd=pf

No person who wishes to continue living should have to die, ever. Check out the post on substack!

I believe that human immortality (increasing healthspan, eliminating causes of death, etc.) is something we as a species ought to urgently work towards. I am not a scientist, so I will primarily talk about the philosophical, political, and governance related implications of longevity.

I intend to increase my knowledge of biology & other important to immortality disciplines because that's enjoyable but also so that I may more accurately evaluate people, policies, and projects in the longevity / immortality space. Any suggestions for increasing my biology knowledge? I'm at about a "took biology for science majors in undergrad plus has read biology popular science books for fun" knowledge level right now.

EDIT 2022/09/13: I've created a Google Group called Immortality Studies to serve as a public discussion & mailing list plus coordination point for all of us interested in getting rid of death. I prefer to communicate about this subject area publicly, but you are welcome to message me here on LessWrong or email me at walambert@pm.me for private conversations (it may take me some time to get back to you since I have little slack in my life right now and am also prioritizing public conversations for coordination & transparency reasons).

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Have you considered getting rid of death?
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[-]mukashi*249

Hi! Biologist (kind of, Biotechnologist and PhD in Bioinformatics) here. 

Biology as a field is way too broad.  You can pick any branch of biology and spend your whole life studying that, there will still be things to learn.  Having said that, and given that you're interested in things related to longevity, I would:

  1. First, be aware of one thing: there is a massive difference between Biology and Physics ( I could make a similar comparison with other sciences, but Physics serves my purpose). Feynman explains that VERY well in his book "Surely you are joking Mr Feynman". Physics students try to develop an intuition about how different models of the world work. Biologists, on the other hand, f**ng adore memorizing names by heart and many old University professors think that it is the right thing to do (e.g. memorizing the names of the molecules involved in the Krebbs cycle).  The result is that most things that Biologists studied at some point are simply forgotten. For instance, I studied a few courses on Plant physiology but if you ask me what is the difference between C3 and C4 plants I have no clue.  So my first piece of advice is, "try to learn Biology as a physicist would do it". Learn the important concepts and learn how to reason about those concepts
  2. Second, develop a solid understanding of Molecular Biology.  I would buy (or borrow) "Molecular Biology of the Cell"  aka "The Albert" and read a few chapters. The concepts you should be very familiar with are:
    1. Replication, transcription, translation
    2. The basics of genetic regulation
    3. Metabolism, especially how the cell obtains energy: respiratory chains,  ATP synthesis, etc. 
  3. YouTube is your friend. There are very good channels out there explaining complex concepts.
  4. Some of the names of molecules and metabolic pathways will be unavoidable important, e.g. caspases. Use Anki to memorize those. This might contradict a bit the first point, but you will need to develop some "general culture" and this requires memorization.  For instance, words you need to be familiar with: respiratory complex system, NADH, telomeres. Words you do NOT be familiar with e.g. Succinate Coenzyme Q Reductase. 
  5. Try to explain the different things that you learn without using their real names.  E.g. can you find an alternative name for every part of the machinery involved in ATP synthesis?  (for example, instead of saying ATP synthase, you could say nano rotor that puts together ADP and P). If you can do that for most things that you learn, you are good to go. 
  6. Read "Power, sex, suicide". It is a popular science book but it has a very good level. If you have spent a few weeks/months reading The Albert, you will understand most of it.
  7. In Biology Evolution is King.  You don't need to understand the in and outs of population genetics, but you certainly benefit from understanding what we know about the origins of mitochondria for instance. 
  8. Speak with biologists and test your ideas with them (in the best case scenario, find people having PhDs). Say to them you think "that we could just do some engineering in the telomerase" and we would solve the longevity problem. Some of them might not follow what you are saying. Search for the person that laughs at this statement and tell him/her to explain why this wouldn't work. That's the guy you want to hang out with. Speak with him and make him ridicule your ideas. If you understand why the things you are proposing do not make sense, this will mean you are learning.
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[-]mukashi134

A couple of things I wanted to add:

  1. There is also a complementary point to point number 1.  I have seen systematically people coming mostly from the physics and mathematics underestimate the complexity of the ideas/problems in Biology.  I have seen a lot of that in LW, so watch out. If someone says that by reading a DNA sample a very powerful computer can derive the moral values of humans, you can bet a lot of money that this person has no clue about biology. To me, it sounds like a biologist saying that the Bayes theorem is false because probabilities are in the mind. Don't become that arrogant prick. Do your homework!
  2. The above list gives you a very solid understanding of molecular biology, certainly more than the vast majority of philosophers. Something missing is probably Physiology. To learn about physiology, use the same ideas above: YouTube, some manual, present your ideas to other people, etc. 
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[-]Willa10

Much thanks for your recommendations & advice, I appreciate you taking the time to share those things!

That's good to know re: the biology vs physics distinction. I'm great at remembering and playing with concepts and also do decently at memorizing all the "hardware bits" so to say (my intellectual & professional background is mixed and requires proficiency with many concepts as well as being able to RTFM a textbook and memorize things).

I will check out the books you mentioned, other sources, and generally do my homework, hehe :) I love physics, but biology is more fun in a few ways BECAUSE of how many more moving parts you have to deal with (biology uses less abstract maps of the territory than physics, usually, ergo there are more moving parts and thus more covarying input parameters in whatever system one's dealing with).

What topics in biology do you classify as "you need a deep or solid understanding of them generally before moving to specific subtopics" type topics vs more specialty topics (you touched on this some I think, are there other helpful topics to learn for longevity research in addition to the ones you mentioned)? Looks like evolution, molecular biology, and physiology are what you mentioned so far.

Any recommendations for networking with biologists and finding good mentors in that space? Besides posting in public forums where they might hangout, heh. (any other good places besides this one?)

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[-]mukashi50

Any recommendations for networking with biologists and finding good mentors in that space? Besides posting in public forums where they might hangout, heh. (any other good places besides this one?)

 

Search a good University around where you live / a place where you can go physically. Go to the tab: Research. Find the biology department. See what they are doing. Read their research. Cold email them. Did wonders for me. 

Besides, happy to have chat on Skype or similar at some point if you fancy

What topics in biology do you classify as "you need a deep or solid understanding of them generally before moving to specific subtopics" type topics vs more specialty topics (you touched on this some I think, are there other helpful topics to learn for longevity research in addition to the ones you mentioned)? Looks like evolution, molecular biology, and physiology are what you mentioned so far.

Start with Evolution and Molecular Biology in parallel first, once you have the basics right, move to Physiology. 

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[-]wolajacy10

Can you please link some of those Youtube channels you mentioned in the comment? I'd like to learn more about the topic - ideally, grasp the big ideas & what-I-don't-know (coming from the pure math angle, so not much grounding in the natural sciences).

For reference, I found Introduction to Biology - The Secret of Life (an MIT course at edX) to be very helpful in this kind of exploration.

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[-]mukashi10

To tell you the truth, I can't think of any right now. The reason is that the things I know about Biology I learnt them mostly using books, interacting with people in my environment, teachers, reading in the internet etc. I just assumed that there must be excellent YouTube channels out there because it is the case for other areas that I actively follow (History, Language learning, etc). I have used YouTube (when YouTube was a baby) to understand things as basic as transcription, which is WAY easier to understand once you see the different parts of the cell interacting. The MIT course you mention, I don't know it, but it is certainly very useful.

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[-]DirectedEvolution60

My suggestion is to pick a specific aging research question and dig into the models, methods and evidence. For example, when people hypothesize that “naked mole rats don’t age,” how do scientists study that hypothesis? How does that inform our concept of “immortality,” and what is the distinction between “being immortal” and “not aging?”

I think you’ll have better luck with this approach than trying to build a very broad, somewhat undirected knowledge of biology. Nothing wrong with broad knowledge, it’s just that only a tiny fraction will be directly pertinent to any particular topic you’re interested in.

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[-]Willa30

I value specificity & find that being too general with research foci or questions hurts both specificity and quality of work, so I agree with what you said. But, I'm not quite there yet regarding investigating narrowly focused hypotheses for specific biology questions. I'm approaching this [writing about immortality] in a few ways:

  • I want to distinguish between longevity and immortality: I believe that longevity refers specifically to increasing human healthspan whereas immortality is the meta cause area which includes longevity (and other cause areas related to not dying) underneath its umbrella but itself [immortality] is specifically: the overall effort to eliminate every possible cause of death (e.g. another germane cause area that isn't longevity could be human mind uploading or mind backup & restore capabilities or indestructibility related body modifications, and more). Part of that distinguishing will involve mapping out other coherent cause areas underneath immortality.
  • There are a ridiculously many causes of death, medical or otherwise, thus I believe a much larger community of people & organizations working in the immortality area needs to exist such that we increase the rate of germane problem solving progress. I want there to be a species-wide project towards immortality that dwarfs even what the Manhattan Project was so part of my writing focus & other work will be explicitly geared towards organizing and community building.
  • I'm deeply concerned about politics & governance in a society with longer lived or immortal humans, this is one area where I will want to get very specific.
  • I want to find a biology research niche or few to explore deeply & write quality research papers in, plus this will help me navigate through quackery and maintain an ongoing eye towards what "real" or decent research in the field looks like. Max Planck had insightful things to say about the issue of non-scientists or non-researchers attempting to navigate the minefield of what's rubbish and what's real in a scientific discipline in The Philosophy of Physics which I took to heart (it's a short book, very good, do recommend).
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[-]DirectedEvolution60

I want to distinguish between longevity and immortality: I believe that longevity refers specifically to increasing human healthspan whereas immortality is the meta cause area which includes longevity (and other cause areas related to not dying) underneath its umbrella but itself [immortality] is specifically: the overall effort to eliminate every possible cause of death (e.g. another germane cause area that isn't longevity could be human mind uploading or mind backup & restore capabilities or indestructibility related body modifications, and more). Part of that distinguishing will involve mapping out other coherent cause areas underneath immortality.

This makes sense. We can actually distinguish three concepts:

  • Immortality: living forever, an unlimited or extremely long expected lifespan.
  • Longevity: decreasing the death rate
  • Anti-aging: decreasing the death "acceleration" that occurs as an organism ages

Naked mole rats don't appear to live as long as humans, so they have lower longevity. However, there is some research showing that naked mole rats don't seem to age, meaning that they are no more likely to die at age 35 than they were at age 3.

An organism could in theory be extremely short-lived, while also not aging. We could imagine a bug that has a 50% chance of dying every day, but always has the same 50% chance per day of dying. By contrast, an American's life expectancy is 78 years of age, but their chance of dying increases year by year once they're past early childhood. I'd like to understand

Best of luck with your research! I'm in a biomedical engineering graduate program and am interested in anti-aging, but haven't researched the subject as I haven't had time. Let me know if you have biology related questions however! 

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[-]Willa10

Thank you! Right now it seems like I'll be doing more organizing than research, but I intend to increase the research I do over time. Organizing in this space (i.e. community building for immortality studies & related things) seems like a comparative advantage for me at the moment relative to other actions.

A minor quibble because I agree with the three concepts you mentioned and how you used them, but I think increasing healthspan covers what you referred to as anti-aging. To increase a human's healthspan, one must necessarily decrease that "acceleration" and also do a few other things: rejuvenation biology, preventative medicine, holistic care (better diets, better & more exercise, etc.).

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[-]RichardJActon50

I have a reading list and recommendations for sources of ongoing news in the longevity/immortality/life extension space in the show notes for the recent special episode of my podcast where my co-host Michael and I discuss ageing and immortality. We are both biology PhDs, my background is in the epigenetics of ageing and Michael's bone stem cells.

https://www.xenothesis.com/53_xenogenesis_ageing_and_immortality_special/

I should add "Immune: a Journey into the Mysterious System that Keeps You Alive" to that list actually.

In particular from that list I recommend these for 'coming at biology from a physics perspective':

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[-]Willa10

Thank you for the resources! I've queued up XenoThesis 53: Ageing and Immortality Special on my podcast player.

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[-]erkenbrand*30

I think the Peter Attia Podcast is a good source for informationen on research about moderate life span extention. https://peterattiamd.com/podcast/

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[-]Willa10

Thanks! What are a few of your favourite takeaways from that podcast?

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[-]ChristianKl20

Learning biology is hard because biological systems are very complex. Given that complexity, biologists are generally happy to search keys under streetlights. 

A lot of the important arguments when it comes to longevity are about making guesses about the territory that's not under the streetlights. The knowledge we have about biology is already quite large, but it's important to always keep in mind that it's far of from being complete.

While learning biology your task is to both learn basic concepts to make sense of other knowledge and also learn about the system of how the knowledge gets produced. 

In Core Pathways of Aging,  John Wentworth for example makes claims about many people in the field approaching the subject wrong. You want to understand claims like that about the nature of the information landscape. 

One aspect of the article is that he talks about transposons as potentially being a very important part of aging. DNA sequencing that can only look at short reads like Ilumnia sequencing, can't tell you how much transposons doublicated. Given that the subject was hard to study, biologist essentially proclaimed that the existing transposons in the human genome don't do much. 

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[-]Arun Johnson21

I am an undergraduate studying chemical engineering, and I've been intending to dive into learning about biology relevant to aging for about a year and a half, with relatively slow progress. I'd be interested in developing a rough schedule of things to learn about alongside you if you're interested.

I'd recommend checking out Laura Deming's blog, which has a list of things to learn about to get familiar with our current understanding of aging.

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[-]mukashi21

If there were a group of people interested in this question, I wouldn't mind organising an online monthly meeting where we try to develop a solid understanding of the causes of aging.

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[-]jmh31

I would find that of interest. I'm far from sure I can make any good contributions but aging and causes thereof is something I am interested in. It is also one I have found to be very overwhelming (I don't have any type of biology or chem background) -- just way to much basic knowledge to try grasping before I can really put things in a good context or start to think at a systems level.

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[-]Willa10

I've created a Google Group to facilitate more conversations on this subject and improve coordination, check out Immortality Studies.

A good LessWrong post about aging we could all read & discuss for such a meetup is johnswentworth's Core Pathways of Aging as recommended by ChristianKI in the above comment (thanks Christian!).

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