Do we not understand enough about the human body? I have heard that we don’t fully understand the mechanism behind aging and this got me wondering. I mean our body seems to be like one of the first things we’d investigate, and yet we seem to know less than I had originally thought.
In: 70
Questions about “cause” are often hard, because they can mean any one of several things. To elaborate consider:
* **What is aging?** Does any form of disability that accumulates over time count? Presumably not, since no-one considers traumatic amputation to be aging. What about the avoidable effects of too much sun exposure, or heavy drinking? Some people argue that aging is not actually a thing at all, but the accumulation of various unrelated types of damage to the organism.
* **How does aging take place?** This is probably along the lines of what you were thinking, but still not a particularly well formed question. For instance, suppose we find that “aging” is controlled by DNA damage, in the sense that if we increase or decrease DNA damage that increases or decreases the amount of aging. OK, that would be an answer. But what controls that? Maybe, for example, DNA damage is directly predicted by reactive oxygen species (ROS) in the cytoplasm. OK, so that’s another answer. But ROS production in itself is regulated. What controls that? And so on.
* **Why do things not not age?** Evolution has solved the problem of building trillion cell organisms from a single set of genetic (and epigenetic) material. Why doesn’t it keep that organism alive once it’s made? To me this is a rather vexing question, and I haven’t seen any well supported answers. Explaining the near ubiquity of aging, IMO, is about as hard, and probably related to, the problem of explaining the near ubiquity of sexual reproduction (among animals and animal like protists, in both cases).
Questions about “cause” are often hard, because they can mean any one of several things. To elaborate consider:
* **What is aging?** Does any form of disability that accumulates over time count? Presumably not, since no-one considers traumatic amputation to be aging. What about the avoidable effects of too much sun exposure, or heavy drinking? Some people argue that aging is not actually a thing at all, but the accumulation of various unrelated types of damage to the organism.
* **How does aging take place?** This is probably along the lines of what you were thinking, but still not a particularly well formed question. For instance, suppose we find that “aging” is controlled by DNA damage, in the sense that if we increase or decrease DNA damage that increases or decreases the amount of aging. OK, that would be an answer. But what controls that? Maybe, for example, DNA damage is directly predicted by reactive oxygen species (ROS) in the cytoplasm. OK, so that’s another answer. But ROS production in itself is regulated. What controls that? And so on.
* **Why do things not not age?** Evolution has solved the problem of building trillion cell organisms from a single set of genetic (and epigenetic) material. Why doesn’t it keep that organism alive once it’s made? To me this is a rather vexing question, and I haven’t seen any well supported answers. Explaining the near ubiquity of aging, IMO, is about as hard, and probably related to, the problem of explaining the near ubiquity of sexual reproduction (among animals and animal like protists, in both cases).
We do understand how aging works. It’s simply accumulated errors in DNA replications. Whenever cells divide, there’s a small chance that the DNA makes errors during this process. This is simply still very difficult to fix, because we still don’t have the technology to repair DNA ourselves.
Also some parts of our bodies are not self-repairing or self-regenerating. If it grows once, then it’s a done-deal. Even if it’s completely self-repairing or self-regenerating, your DNA may also not anticipate how you would be like in hundreds or thousands of years. So there’s no guarantee that even this approach would make you immortal.
If we want to become immortal, then the way we heal ourselves should be unique to every injuries and errors that we make. It should be continuous and adapt to every situations.
We do understand how aging works. It’s simply accumulated errors in DNA replications. Whenever cells divide, there’s a small chance that the DNA makes errors during this process. This is simply still very difficult to fix, because we still don’t have the technology to repair DNA ourselves.
Also some parts of our bodies are not self-repairing or self-regenerating. If it grows once, then it’s a done-deal. Even if it’s completely self-repairing or self-regenerating, your DNA may also not anticipate how you would be like in hundreds or thousands of years. So there’s no guarantee that even this approach would make you immortal.
If we want to become immortal, then the way we heal ourselves should be unique to every injuries and errors that we make. It should be continuous and adapt to every situations.
>Do we not understand enough about the human body?
We don’t, no, primarily because it’s really, really, really, really complicated.
Here’s a map of [human metabolic components](https://metabolicatlas.org/explore/Human-GEM/map-viewer/endoplasmic_reticulum?dim=2d&panel=0&sel=&search=&coords=-10136.19,-107123.49,0.05,0,0,500&dataTypes=None&dataSources=None&dataSets=None). It’s specific to the endoplasmic reticulum, and not all are even shown. The schematic for metabolic reactions taking place in the cytosol has six parts. You can see the ones for the other organelles of a cell too: the mitochondria, the golgi, lysosomes and peroxisomes. What you’re seeing here, is a map of the chemical reactions that take place to keep life living.
And this is just the metabolism. Each metabolic step has one or more protein enzymes that have to get made in order to allow the chemical reaction to take place. The enzymes have to get transcribed from DNA. There’s a bunch of DNA replication that happens. That’s the genetic level at which life lives.
Every cell has a slightly different selection of all of these happening inside of it, because different cells need to perform different behaviors in order to keep the body functioning. Then there are cell-specific processes that have to happen. Life at the cellular scale has its own rules that are an emergent property of the genes and the chemistry.
And it’s not all about the cell. The cells themselves need to be sewn together in a way that produces functional organs. There’s an entire extracellular matrix that has to stay functioning. And some of these extracellular components are things you know: bones, tendon, skin. Life has to work at the level of organ systems.
If any of these, either the cells or the extracellular matrix or the big extracellular components like bones or skin get damaged, the cells of the body need to perform special functions that heal that damage. The body needs to maintain itself, and the cells need to be constantly adapting and changing their behavior depending on what the body needs. Life needs to heal itself and self-regulate, that’s a core function of staying alive.
To power all of this healing — and not just healing, growth too, ideally, if at the appropriate phase of life for that — we need enough fuel of various different kinds. We need caloric ones like sugars and fats, but also certain vitamins and minerals that you need to eat and they aren’t interchangeable with other food. That’s the nutrition life needs to survive.
The body is immensely, immensely, immensely complicated, and aging *can* cause and be caused by changes in pretty much any and all of that at once. Indeed, aging *usually* involves changes in pretty much all of that at once. Genes start shutting down, changing which chemical reactions take place. Bones get brittle, making tasks more difficult. As muscle mass is lost, the proteins needed to heal reduce in availability. As our digestive system ages, the nutrition we take in changes.
We know lots of mechanisms of aging. But aging is a lot of things happening all at once. That’s why we can say “we don’t know the mechanism of aging”, because the body’s really complicated and we don’t really know for sure why all of the things that happen during aging happen during aging.
>Do we not understand enough about the human body?
We don’t, no, primarily because it’s really, really, really, really complicated.
Here’s a map of [human metabolic components](https://metabolicatlas.org/explore/Human-GEM/map-viewer/endoplasmic_reticulum?dim=2d&panel=0&sel=&search=&coords=-10136.19,-107123.49,0.05,0,0,500&dataTypes=None&dataSources=None&dataSets=None). It’s specific to the endoplasmic reticulum, and not all are even shown. The schematic for metabolic reactions taking place in the cytosol has six parts. You can see the ones for the other organelles of a cell too: the mitochondria, the golgi, lysosomes and peroxisomes. What you’re seeing here, is a map of the chemical reactions that take place to keep life living.
And this is just the metabolism. Each metabolic step has one or more protein enzymes that have to get made in order to allow the chemical reaction to take place. The enzymes have to get transcribed from DNA. There’s a bunch of DNA replication that happens. That’s the genetic level at which life lives.
Every cell has a slightly different selection of all of these happening inside of it, because different cells need to perform different behaviors in order to keep the body functioning. Then there are cell-specific processes that have to happen. Life at the cellular scale has its own rules that are an emergent property of the genes and the chemistry.
And it’s not all about the cell. The cells themselves need to be sewn together in a way that produces functional organs. There’s an entire extracellular matrix that has to stay functioning. And some of these extracellular components are things you know: bones, tendon, skin. Life has to work at the level of organ systems.
If any of these, either the cells or the extracellular matrix or the big extracellular components like bones or skin get damaged, the cells of the body need to perform special functions that heal that damage. The body needs to maintain itself, and the cells need to be constantly adapting and changing their behavior depending on what the body needs. Life needs to heal itself and self-regulate, that’s a core function of staying alive.
To power all of this healing — and not just healing, growth too, ideally, if at the appropriate phase of life for that — we need enough fuel of various different kinds. We need caloric ones like sugars and fats, but also certain vitamins and minerals that you need to eat and they aren’t interchangeable with other food. That’s the nutrition life needs to survive.
The body is immensely, immensely, immensely complicated, and aging *can* cause and be caused by changes in pretty much any and all of that at once. Indeed, aging *usually* involves changes in pretty much all of that at once. Genes start shutting down, changing which chemical reactions take place. Bones get brittle, making tasks more difficult. As muscle mass is lost, the proteins needed to heal reduce in availability. As our digestive system ages, the nutrition we take in changes.
We know lots of mechanisms of aging. But aging is a lot of things happening all at once. That’s why we can say “we don’t know the mechanism of aging”, because the body’s really complicated and we don’t really know for sure why all of the things that happen during aging happen during aging.
We know lots of things that contribute to ageing, as others have said, “ageing” is a broad term. There is evidence that we accumulate more cells that do not behave as they should and are functioning improperly. Some researchers say these cells have mutations in their DNA, essentially that the instructions for making proteins (the machinery that makes cells function) are broken. Some say that the cells don’t function due to epigenetic issues (the bookmarks on the DNA that allow it to be read or not). These junk cells then cause lots of issues, they may divide too much or interfere with nutrient or oxygen transport, and they may just do nothing. There is debate about what comes first and which factors are the most important.
We know lots of things that contribute to ageing, as others have said, “ageing” is a broad term. There is evidence that we accumulate more cells that do not behave as they should and are functioning improperly. Some researchers say these cells have mutations in their DNA, essentially that the instructions for making proteins (the machinery that makes cells function) are broken. Some say that the cells don’t function due to epigenetic issues (the bookmarks on the DNA that allow it to be read or not). These junk cells then cause lots of issues, they may divide too much or interfere with nutrient or oxygen transport, and they may just do nothing. There is debate about what comes first and which factors are the most important.
An emerging way of framing aging is as cellular information loss.
Your cell doesn’t know how old it is, in fact most cells are constantly either dividing or being renewed from stem cells (also dividing).
This means there are few cells as old as you are. Your cells don’t know if you are 15 or 150. In fact there are plenty of examples of longer lived species (whales, trees, turtles etc)
So it must be the information that the new cell gets from the old cell that is somehow getting “older.”
This means it must be connected somehow to DNA, since the rest of the new cell gets built from the DNA of the old cell.
This is like having to build a new building every time from a blueprint but during construction and while you have the building your blueprint keep getting coffee stains and tears and scratches on it. You keep repairing it but eventually the mess adds up and the blueprint stops being readable. You lose track of which floor gets the stairs and where the foundations go.
The DNA equivalent of a coffee stain is DNA damage (from UV, free radicals, that ultra-processed fluorescent mac &cheese you ate etc). This damage is usually repaired but sometimes it gets repaired wrong, and you get mutations and epigenetic drift, a fancy way of saying the wrong parts of the DNA become silent and active.
Once this information is lost, there is no easy way to fix it, since your cell doesn’t have a third copy. In fact this is the reason you get two DNA strands to being with, it’s more robust than just one.
One solution is you can get rid of the old cell, which your body does all the time, but eventually you run out of “fresh” cells or stem cells, since they too get too much information loss and noise.
Without a way to return this information to the cell, I.e fix the blueprint, eventually cells start to grow out of control (cancer) or start being toxic (senescent), or just don’t work really well.
Eventually tissue and organs start to fail and something important stops working, which kills you. We can this dying of old age.
This means that although it’s absolutely complex and multifaceted, there’s actually a central locus we can target: DNA information loss in the cell. There are now numerous startups working on this issue, and really ground breaking work happening in this area.
How come we don’t have any idea what latest? It will be interesting to see with all of this data crunching and problem-solving is AI has some answers in the next few years. But it’s a very good question
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