May 23, 2007
Newest Brain Neurons Learn More Easily
New neurons continually formed in the brain from neural stem cells are more plastic and probably enhance learning abilities.
The steady formation of new brain cells in adults may represent more than merely a patching up of aging brains, a new study has shown. The new adult brain cells may serve to give the adult brain the same kind of learning ability that young brains have while still allowing the existing, mature circuitry to maintain stability.
These results are good news for the future of rejuvenation therapies. The development of replacement youthful neural stem cells to replace aging neural stem cells will likely boost learning ability in aging minds.
The brain is going to be the hardest organ to rejuvenation because most of it will need to be repaired rather than replaced. Replacement using stem cells will become possible before repair using gene therapy and nano repair robots.
Newly formed nerve cells behave in a more youthful manner than cells that have been neurons for longer periods of time.
Hongjun Song and colleagues reported their findings in the May 24, 2007 issue of the journal Neuron, published by Cell Press.
In their experiments, they used a virus to selectively label new brain cells with a fluorescent protein in the hippocampus, a major brain center for learning and memory, of adult mice.
The researchers then analyzed the electrophysiological properties of the new neurons at different times after their formation. This analysis enabled them to measure how adaptable, or "plastic," the brain cells were.
The researchers found that the new adult neurons showed a pattern of changing plasticity very similar to that seen in brain cells in newborn animals. That is, the new adult brain cells showed a "critical period" in which they were highly plastic before they settled into the less plastic properties of mature brain cells. In newborn animals, such a critical period enables an important, early burst of wiring of new brain circuitry with experience.
What’s more, the researchers’ molecular analysis showed that the plasticity of new adult neurons depended on the function of one of the same types of receptors that is associated with learning-related processes in newborn animals. Such receptors are the receiving stations for chemical signals called neurotransmitters, launched from neighboring neurons to trigger a nerve impulse in the receiving neurons. Subtle alterations in receptor populations are the means by which the brain wires the preferred pathways in the process of learning and memory.
Part of the loss of plasticity is probably due to age. But some of the loss of plasticity might be by program. Once a neuron has been around for a while it has probably found some purpose and there's probably a bias in the brain's design against letting a neuron too easily get reprogrammed for other purposes.
This supports an old idea of mine (and probably many others). It is commonly assumed that rejuvenation of the body is not a problem since it can be replaced, but the brain has to be repared and not replaced. Why not replace the brain ? Because the identity and the memory of the patient disappears and the patient does not want this. What about replacing 2% of the brain each year ? The patient will hardly notice and definitely not complain. There is in fact a continuous scale between replacing 0 % of the brain per year and 100 % per year. This raises unanswerable questions about identity, less serious than those raised in the anthology "The minds eye" collected by Douglas Hofstadter. Un answerable questions but still interesting.
Nevertheless, replacing 2% of the brain each year would work and adds one more possibility for eternal life while keeping ones identity. The other possibility is of course to repair every cell in the brain in addition to removal of all extracellular junk and so on.
That's a very interesting point, mats-Erik Pistol. We wouldn't necessarily mind temporarily not have access to certain regions of the brain while they're being regrown. Go on a retreat for some months while your Hippocampus is being regrown.
Er, the Amygdala would be a better example.. the Hippocampus could still be problematic.
mats-Erik Pistol's idea of the incremental regeneration of the brain is one I thought of as well when I first heard about "stem cells" in the mid 90's. I'm sure many others have thought of this as well. There are philosophical issues of identity and continuity involved here, but it strikes me that this is the way to cure the aging problem in the case that aging really is caused by random genomic DNA damage (which is hotly debated by Aubrey de Grey). The important fact here is that such a stem cell regeneration offers a method of regeneration and incremental replacement cure of aging of an effectiveness that is model-independent of whatever the actual causes of aging on.
The philosophical issues of identity and continuity that such an incremental replacement of the brain involve here are ones that I considered considerably during the 90's. The fact that I lived as an expat in Asia from 1991-2001 has had an enormous influence on how I have answered these issues for my personal situation.
As a comment to Kurt9, I would say that random genomic DNA damage cannot be the cause of aging, since cloning using cells from old animals (which has been done by Advanced Cell Technology if I remember correctly) does not result in clones that are "old" at birth. I also don´t think one should replace subunits of the brain one by one, such as the hippocampus or parts of the corpus callosum, rather a general substitution all over. 2%/year is less than 0.2%/month and if done on a weekly basis would be completely unnoticeable, bypassing any objection from an identity/continuity point. Aging after the age of 50 probably causes a faster decay than 2%/year.
So our hope is that simple stem cell therapy of the type where stem cells are simply injected into the blood or cerebrospinal fluid will find and replace old or dead brain cells. A faint hope I admit but not impossible.
We might also be so lucky that mitochondrial genetic damage is not a cause of aging either, in which case we are in much better shape to cure aging since the other causes of aging (according to Aubrey de Grey) are so much easier to fix, with the possible exception of glycolysed proteins.
I just thought of the same thing right after I wrote my last comment this morning. Cloning itself suggests that genomic DNA damage cannot be a cause of aging. However, it will be a problem in the long run (when we are around 200 or so). So, we might as well solve the problem now rather than wait until later.
I do think (like absolutely convinced) that mitochondrial DNA damage is a primary cause (maybe the only cause) of aging. However, this is not as difficult as one might think to fix. This is what caught my interest in Aubrey's papers back in '99, before his SENS idea. Also, there are a lot of people (who do not know Aubrey from Adam) who are working on this problem. There are a considerable number of papers in PubMed about the "mitochondrial-lysosomo axis" theory of aging and how to fix it.
I believe that stem cell regeneration from the hypothalamus and other places will result in a gradual replacement all over the brain.
I have one problem with the mitochondrial theory of aging. Eggs have old mitochondria as well, but nevertheless the embryos are as new every generation. A friend of mine tells me that eggs are selected by spontaneous abortions and only the ones with healthy mitochondria go to term. However the fraction of embryos that are aborted is not very high. So, how can egg mitochondria avoid genetic damage ?
I did not find any papers at a first look, about how to fix or delete damaged mitochondria. Head transplant to a cloned twin who was never allowed to be conscious ? Still need to fix the head and brain, though.
My understanding is that the mitochodria somehow get "reset" when the ova is produced (someone explained the details to me to me once and I have forgotten them) in the woman's body. It is also known that ova from older birth mothers is of lower "quality" than that of younger birth mothers. Even though the risks of congenital problems (Down's, etc.) increases, this does not seem to reduce life expectancy in the kids in the absence of such congenital problems.
Do a PubMed search on "lysosomal" and "mitochondria" together as search terms. Among the abstracts that show up, you will see some that reference the "lysosomal-mitochondrial axis" as a cause of aging.
Aubrey's SENS is one proposal to solve mitochondrial aging. There is another method being pursued by a start-up company that i recently ran across on the net (I can't find the details) that also aims to solve this problem.