4 ms·

I tend to think of aging as an overall degradation of the system. For instance, there’s loss of hair cells in the ear that reduces hearing higher frequencies. T

by dnhz 7y ago

I tend to think of aging as an overall degradation of the system. For instance, there’s loss of hair cells in the ear that reduces hearing higher frequencies. There’s clouding of the eye lens as the proteins there aggregate. Long lived cells like neurons accumulate oxidation and probably die at some slow rate. I can’t quite see how drugs which modulate existing biochemical pathways can stop, let alone reverse the processes I’ve named.

partingshots 7y ago
That’s a very good summarization of the problems we face in dealing with aging. No drug can fix the damage that is caused by it. We have very early therapies that try to jumpstart or uplift existing biological machinery like the various immunotherapies currently being targeted towards cancers, but that’s still just taking advantage of what is inherent to our bodies. Over time these processes inevitably begin to fail. You have to engineer new machinery to replace/repair the failing processes for any chance at real longevity. The kind of things that will be capable of doing something like that will be extraordinarily complex, and to compare the drugs we have available today is akin to comparing an abacus to a modern supercomputer.
naasking 7y ago
> I can’t quite see how drugs which modulate existing biochemical pathways can stop, let alone reverse the processes I’ve named. I'm honestly mystified why this would be a mystery. Your cells have the blueprint to grow a whole new body, but clearly many of these pathways are dormant. Is it really so far fetched that a drug could reactivate some of these pathways? Like, why is there a loss of hair in the ear when for the first few years of life, that hair grows instead of dies? There is even evidence that age reversal can and has been done: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028 https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028 https://www.sciencedirect.com/science/article/pii/S0092867418301521 https://www.sciencedirect.com/science/article/pii/S009286741...
- dnhz 7y ago
  The body forms structures over the course of development. But I don’t think it can replay those actions again. In places like the knee and eye lens, the cells that formed those structures did their job and dissolved their nuclei. I’m more familiar with the eye lens example so let’s go with that. The cells there are just bags of proteins and antioxidants. No nuclei, no mitochondria, no activity. Oxidation from the environment gradually damages those proteins and lead to cataracts. Everyone would eventually get cataracts if they could live forever. DNA is not enough. There was coordination in time and space to construct the body during development, and the growing body has no damaged cells and structures to deal with.
  - naasking 7y ago
    Eye damage repair: https://www.biorxiv.org/content/10.1101/710210v1 https://www.biorxiv.org/content/10.1101/710210v1 Also, the cornea does heal from some damage, so clearly it's not just passive tissue.
Erlich_Bachman 7y ago
> I tend to think of aging as an overall degradation of the system Why do you do that? Why would you think it is correct? To my knowledge that's a wrong interpretation. Yes there is constant continuous damage to DNA and cells etc. But the body has mechanisms to repair that damage. It is the repairment that slows down during aging, and that is programmed by genetic and biological processes, like everything else in the body. Biologically, a cell can keep reproducing over and over again, it is no problem.
- dnhz 7y ago
  Put it simply, there is reversible damage and irreversible damage. Oxidized protein aggregates that the cell can’t degrade are an example of irreversible aggregates. Amyloid protein fibrils, although no longer implicated in disease, are another example of a stable, irreversible state. The process of repair slows down not due to programming but because the cells of the body get progressively worse at identifying and repairing damage, because the very machinery that carries out these processes, proteins, get damaged.

by dnhz 7y ago

partingshots 7y ago

That’s a very good summarization of the problems we face in dealing with aging. No drug can fix the damage that is caused by it. We have very early therapies that try to jumpstart or uplift existing biological machinery like the various immunotherapies currently being targeted towards cancers, but that’s still just taking advantage of what is inherent to our bodies. Over time these processes inevitably begin to fail. You have to engineer new machinery to replace/repair the failing processes for any chance at real longevity. The kind of things that will be capable of doing something like that will be extraordinarily complex, and to compare the drugs we have available today is akin to comparing an abacus to a modern supercomputer.

naasking 7y ago

> I can’t quite see how drugs which modulate existing biochemical pathways can stop, let alone reverse the processes I’ve named. I'm honestly mystified why this would be a mystery. Your cells have the blueprint to grow a whole new body, but clearly many of these pathways are dormant. Is it really so far fetched that a drug could reactivate some of these pathways? Like, why is there a loss of hair in the ear when for the first few years of life, that hair grows instead of dies? There is even evidence that age reversal can and has been done: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028 https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028 https://www.sciencedirect.com/science/article/pii/S0092867418301521 https://www.sciencedirect.com/science/article/pii/S009286741...

dnhz 7y ago
The body forms structures over the course of development. But I don’t think it can replay those actions again. In places like the knee and eye lens, the cells that formed those structures did their job and dissolved their nuclei. I’m more familiar with the eye lens example so let’s go with that. The cells there are just bags of proteins and antioxidants. No nuclei, no mitochondria, no activity. Oxidation from the environment gradually damages those proteins and lead to cataracts. Everyone would eventually get cataracts if they could live forever. DNA is not enough. There was coordination in time and space to construct the body during development, and the growing body has no damaged cells and structures to deal with.
- naasking 7y ago
  Eye damage repair: https://www.biorxiv.org/content/10.1101/710210v1 https://www.biorxiv.org/content/10.1101/710210v1 Also, the cornea does heal from some damage, so clearly it's not just passive tissue.

Erlich_Bachman 7y ago

> I tend to think of aging as an overall degradation of the system Why do you do that? Why would you think it is correct? To my knowledge that's a wrong interpretation. Yes there is constant continuous damage to DNA and cells etc. But the body has mechanisms to repair that damage. It is the repairment that slows down during aging, and that is programmed by genetic and biological processes, like everything else in the body. Biologically, a cell can keep reproducing over and over again, it is no problem.

dnhz 7y ago
Put it simply, there is reversible damage and irreversible damage. Oxidized protein aggregates that the cell can’t degrade are an example of irreversible aggregates. Amyloid protein fibrils, although no longer implicated in disease, are another example of a stable, irreversible state. The process of repair slows down not due to programming but because the cells of the body get progressively worse at identifying and repairing damage, because the very machinery that carries out these processes, proteins, get damaged.