12 replies to this topic

[olaf.larsson]

Suppose all chemical aging processes were terminated. Why do you assume that the body will not sooner or later loose its integrity anyway, by slow mechanical deformation etc. Why wouldn´t the "non agning" human sooner or later human become "deformed" by mechanical stress to a state which would be life threatening?

[jaydfox]

Two questions.

First, which mechanical features do you anticipate will become deformed to such a degree? Most of our tissues are pliable and repairable. Stretched skin can retract to its former size, within reason. Obviously, we've all seen pictures of people who have lost 200 pounds, and their skin does not fix itself. I consider this problem separate from "aging", even though the effect is similar (sagging skin, etc.). Bones are another organ I'd worry about, although if we could give bones more ability to regenerate in old age, I suppose they could maintain their shape quite a bit better.

So this leads to my second question. What timeframe are we talking about? Given how long bodies last as it is, I can't imagine mechanical deformation mattering in anything less than a couple lifetimes, and probably not in anything less than a great many lifetimes, i.e. on the scale of millenia. But at some point, I'm left to wonder whether such slow accumulation of mechanical deformation can't be handled by regenerative-enabled tissues that are adept at maintaining their shape. The only potential problem, and I'm purely guessing on this, is that cells don't have a strong grasp of where they are and where they are supposed to be. Within their local matrix, perhaps, but can a tissue that is undergoing regeneration accurately maintain its shape, rather than just regenerating a similar, almost but not identical shape? Several iterations of this process could lead to a gradual accumulation of spatial errors.

At any rate, it's a problem on a much slower scale than cancer and other subcellular problems, and a problem that I suspect will also be easier to solve, so by and large, I think it's a low priority issue, if it's an issue at all.

[John Schloendorn]

Mechanical information can be supplemented from external sources, just like chemical one. Perhaps any future ENS will involve periodic transplantation of at least some constructs that have been tissue engineered ex vivo on an artificial scaffold. These "mechanically rejuvenated" tissues can then in turn serve as scaffolds for in-vivo regeneration of others.

[olaf.larsson]

I'm purely guessing on this, is that cells don't have a strong grasp of where they are and where they are supposed to be.

Yes thats the problem as I see it. As long as the body is growing the cells can be moved to their possitions by the growth. As soon as the body is fullgrown there are mechanisms to hold the parts in the possitions they are supposed to be, but this mechanism can not work perfectly. There can not be any mechanisms which organise the most fundamental level of organisation becouse this mechanism would have nothing to relate to. Once this fundamental level of organisation is altered it can not be "repaired".
I hope you understand what i mean...

[John Schloendorn]

ability of cells to respond to existing cues is altered rather than the cues themselves

In bone marrow, either seems to be the case. Young hematopoietic stem cells in old recipients seem as clueless as old cells in young recipients, although the nature of their cluelessness is somewhat different. [1] Thanks for the paper by the way [thumb]

[olaf.larsson]

You're suggesting that the signaling landscape alters fundamentally after a certain developmental stage.

No. Is the body a just a cell culture with cells swimming around? The body could be considered as a cellculture but it also has a macrolevel of organisation, it actually has a form which the individual cell can not be aware of. This problem is not affecting individual cells since individual cells maintain their form mostly by electrical hydrofobic forces holding them in a round shape. Why would the macrolevel of organisation be unchanged for ever? Why do you assume that my foot would not be deformed after 500 years of walking?

[jaydfox]

You're suggesting that the signaling landscape alters fundamentally after a certain developmental stage. I would tend to disagree. I believe that the ability of cells to respond to existing cues is altered rather than the cues themselves. We find that stem cells have homing abilities we are only beginning to appreciate.

I think the important distinction is that during growth, some areas can grow faster than others to compensate for deviations from the "correct" design. In fact, relative rates of growth are ultimately what will determine the shape during growth (well, rates of growth, and the degree to which they are held in place by the matrix).

However, once development has stopped, if a deformation begins, how to the cells know, and even if they knew, how do they correct the problem?

[eternaltraveler]

Whether or not this might happen over an extreme timeframe doesn't seem to much of a big deal. As you say the results will be macro, and thus repairable even by the surgical methods available right now.

[olaf.larsson]

Modern medicine is entirely founded on the premise that the body has a tremendous ability to heal.

I agree on that one, and I have never said that the body doesn´t have "tremendous ability to heal". I dont think really you understand what I mean. Logic says me that there must be a fundamental level of organisation which all other systems must in the end refer to, when for example doing healing. Once this level of organisation is altered there can be no healing of this level becouse there is nothing to refer to how the healing should be done.

[olaf.larsson]

In any case, look to very long lived species for examples that mechanical deformation is not a real issue.

I agree that mechanical deformation is not rate limiting for human lifespan right now.