Regeneration Is Not Rejuvenation

Attila Chordash of Pimm thinks we can get further along in the healthy life extension path using just stem-cell based regenerative medicine than I do.

Systemic regenerative medicine is a coherent and inclusive engineering approach to eliminate all aging related problems indefinitely. Systemic regenerative medicine theoretically means the continuous, gradual and consecutive regeneration of every tissue and organ of the human body n times by combined regenerative medicine approaches, i.e. tissue engineering (in vitro grown organs and tissues implants or parts of them), systemic (via circulation) and locally targeted stem and progenitor cell transplantation, and endogenous stem cell niche activation with proper growth factor delivery aiming to maintain the physiological turnover and condition of the human body.

Which may be the case, and you never know for sure until the job is either done or failed. It seems to me I have the more defensible position, if somewhat less clearly articulated - but I'd be happy to proven wrong on this topic, given that the field of regenerative medicine is well on the way to become a behemoth to dwarf the cancer research community. No need for the years-long process of building up understanding, support, funding, institutes and enthusiasm - all those early days are behind us for regenerative medicine, tissue engineering and similar areas of research. Great and rapid progress lies ahead.

But, inconveniently, regeneration is not rejuvenation. Salamanders still grow old and die, as do the impressive mice of Ellen Heber-Katz. What Chordash is discussing is much more than assisted healing processes culled from the natural world, of course - it's more like the replacement scenario I touched upon a few days ago. Chordash sees this arriving sooner than I would predict:

Hypothetically, yes, pretty much everything except your brain is open to replacement just as soon as scientists can figure out how to build and install those replacements in a useful manner. That's a high bar, however. Your body isn't easily divided into piecemeal components; it's an overlapping bundle of interlinked, complex components - age-related damage to one system may make many related replacements useless or even counterproductive. Developing the technology base for safe replacement of the entire aging body is a long term project - not impossible, but certainly not something that you'll be seeing any time soon.

In order to make yourself physically younger, you must remove the molecular damage of aging within cells - either by replacing cells (such as entire stem cell populations) with less damaged cells, or by repairing that damage. Those are much the same thing if you want to replace cells with more of your own cells grown to order; you have to find a way to repair the damage of aging inside cells one way or another. You can't just regenerate - you must also rejuvenate by repairing this damage to cellular mechanisms.

Which is not to say that regeneration is worthless. The control of stem cells will drive an amazing series of advances in medicine, and quite possible provide the decade or two of additional healthy life that the system biologists think they can manage. There's great value and additional years in repairing broken hearts, blocking the source of cancer and doing everything else you can do at the level of cells.

But I don't see us progressing to a sufficient level of prowess in terms of replacing all systems in the body - and developing a strategy for the brain based upon cellular replacement and regeneration - to greatly extend the healthy human life span more rapidly than we can by following a path more like the Strategies for Engineered Negligible Senescence. The overwhelming question is not "is radical life extension possible?" Of course it is; the laws of physics and our understanding of biology are quite clear on that count. The question is whether we will live to see it - and I doubt that a technology base built only upon regenerative medicine and replacement can possibly advance fast enough and far enough for that.

Which means we have a lot of work to do. But we knew that - and how much better that position is than the experience of those who lived and died before us! We have a chance, and should seize it.

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I'm not so sure...

How many stem cells does an average human get at birth?

Do we have a set number of stem cells which are periodically released, or just a set capacity to generate them?

If so, then it's entirely possible we just run out of stem cells.

If this is the case, replenishing them (and using other strategies to avoid damage, e.g. alagebrium, carnosine, ALC, ALA, resveratrol etc.) supplimentation might very well stave off decrepitude for quite some time.

IMO, it's not a matter of finding the "magic bullet", but rather developing a set of proven strategies that extend life span. This has the dual effect of giving you a chance to live long enough to possibly enjoy the next breakthrough, and even if that doesn't happen, you still had the opportunity to enjoy the benefits of a longer life than you would otherwise.

Personally, I'm not sure I'd like to experience more than several centuries on this planet... But I'd sure love to have to make that decision!

Posted by: Dave Narby at February 17th, 2007 3:14 PM

Regeneration is only an aspect of rejuvenation, but I'd wager it's probably the most important one. Other things like waste product buildup probably aren't risks with fully healthy young cells which we regenerate. Even if we do need specific procedures for it, having robust and replacable cells increases chances of surviving such chemical therapies.

By inserting our DNA into stem cells, the state of our presense cells doesn't matter, save for our DNA. The main risk would be in its gradual compromise over time, which is why we need to do comparisons for mutations as well as telomere monitoring. As for mitochondrial DNA, it probably doesn't vary enough between humans to seriously affect us if it happens to be someone else's, though I'm sure we could rejuvenate our own easier than rejuvenating our nucleus.

Posted by: Tyciol at February 19th, 2007 1:30 AM

I'm not sure the salamanders are the best comparison. While they do regenerate, is what they're able to do as universally encompassing as focused technological conscious applications of stem cell therapies? I can't help but think we'd be able to target things much better and more broadly than the regeneration mechanisms evolved in certain species which are probably specific to certain tasks, like regrowing a leg, which might not affect (I don't know, not being a reptilologist) certain parts, like a liver.

As for not replacing the brain... obviously you can't replace it all in one go like a limb, however with stuff like circulatory stem cells, I don't see why you can't replace bit by bit through simple maintenance, the brain bits. Obviously parts that need replacing are dysfunctional anyway, so they likely are not contributing much to a personality (and if so, in a negative way) as the remaining healthy cells are.

So let the new cells get in, and link up with the old ones as the personality reconstitutes itself by adapting the neural network with the new materials.

Posted by: Tyciol at February 19th, 2008 12:32 AM

Tyciol: Agreed that we may be able to replace the damaged parts of the brain bit by bit in the future, but dosent this replacement have its inherent limitations? I mean we may never be able to replace those neurons which are involved in memory (say in ther hippocampus region)as even the newer neurons (introduced as a result of stem cell therapy)will not be able to form synapses with the existing neurons the way the older neurons did because such synapses are formed as a result of interactions of a person with the enviornment over the years of his life. how can this be replicated.

Also, I feel that there's a limitation to stem cell therapy as there are evidences now that the microenviornment of the cell plays a huge role in the deciding the fate of stem cells i.e. to say that the efficiency of stem cells in treatment of various degenerative diseases would decline with age. The solution to this could be the advent of cellular & molecular repair technologies (future nanomedicine - nanobots)i.e. rejuvinative medicine in true sence. But this probably will take a lot longer. Till then I suppose stem cell therapy might prove to be our best bet in the near future.

Posted by: nanohelix at March 4th, 2008 11:00 PM
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